Author: "A. Collier" / Topic: medicine - Searchworks@Jio Institute Digital Library Search Results

7,457 results on '"A. Collier"'

1. A python library for the fast and scalable computation of biologically meaningful individual specific networks

Author: Giada Lalli, Zuqi Li, Federico Melograna, James Collier, Yves Moreau, Daniele Raimondi, and Kristel Van Steen
Subjects: Individual specific networks, Network analysis, Biological networks, Medicine, Science
Abstract: Abstract Individual Specific Networks (ISNs) are a tool used in computational biology to infer Individual Specific relationships between biological entities from omics data. ISNs provide insights into how the interactions among these entities affect their respective functions. To address the scarcity of solutions for efficiently computing ISNs on large biological datasets, we present ISN-tractor, a data-agnostic, highly optimized Python library to build and analyse ISNs. ISN-tractor demonstrates superior scalability and efficiency in generating Individual Specific Networks (ISNs) when compared to existing methods such as LionessR, both in terms of time and memory usage, allowing ISNs to be used on large datasets. We show how ISN-tractor can be applied to real-life datasets, including The Cancer Genome Atlas (TCGA) and HapMap, showcasing its versatility. ISN-tractor can be used to build ISNs from various -omics data types, including transcriptomics, proteomics, and genotype arrays, and can detect distinct patterns of gene interactions within and across cancer types. We also show how Filtration Curves provided valuable insights into ISN characteristics, revealing topological distinctions among individuals with different clinical outcomes. Additionally, ISN-tractor can effectively cluster populations based on genetic relationships, as demonstrated with Principal Component Analysis on HapMap data.
Published: 2024
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2. Assessing if motives-based vignettes influence plans for drinking and alcohol cues: protocol for a randomised controlled trial

Author: Richard Cooke, Gillian Shorter, Marcus Bendtsen, Katarina Ulfsdotter Gunnarsson, Joel Crawford, and Elizabeth Collier
Subjects: Medicine
Abstract: Introduction In Sweden and the UK, there is a high prevalence of risky drinking, a pattern of drinking associated with adverse consequences. Drinking motives are a proximal predictor of risky drinking and subsequent consequences, suggesting it may be an apt intervention target. Currently, there is a lack of evidence regarding the applicability of motives for intervention efforts. The current study aims to test if motives-based materials are effective in impacting plans for future drinking and reactivity to alcohol-related cues. A secondary aim is to assess individuals’ perceptions of risky drinking as outlined by health authorities. The results of the study will inform the design of a motives-based digital alcohol intervention.Methods and analysis The study is a three-arm, parallel group, randomised controlled trial. Vignettes will be used to present health information, framed in terms of gains from limiting drinking and losses from excess drinking. Control vignettes will present general health information framed in terms of gains or losses. Proxies for behaviour (intentions and self-efficacy) will be assessed with questionnaire items. A Stroop task will be used to assess reactivity to alcohol cues, and an open-ended item will be used to record perceptions of risky drinking. Outcomes will be contrasted with regression models and estimated using Bayesian inference, while qualitative data will be analysed using thematic analysis within a framework analysis.Ethics and dissemination Ethical approval for the study was waived by the Swedish Ethical Review Authority on 16 December 2023 based on participants being anonymous (Dnr. 2023-06474-01). The results of the study will be disseminated in an academic journal and research conferences while also informing the design of a national digital alcohol intervention.Trial registration number ISRCTN12456514.
Published: 2024
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3. Design and testing of ultrasound probe adapters for a robotic imaging platform

Author: Krysta-Lynn Amezcua, James Collier, Michael Lopez, Sofia I. Hernandez Torres, Austin Ruiz, Rachel Gathright, and Eric J. Snider
Subjects: Medicine, Science
Abstract: Abstract Medical imaging-based triage is a critical tool for emergency medicine in both civilian and military settings. Ultrasound imaging can be used to rapidly identify free fluid in abdominal and thoracic cavities which could necessitate immediate surgical intervention. However, proper ultrasound image capture requires a skilled ultrasonography technician who is likely unavailable at the point of injury where resources are limited. Instead, robotics and computer vision technology can simplify image acquisition. As a first step towards this larger goal, here, we focus on the development of prototypes for ultrasound probe securement using a robotics platform. The ability of four probe adapter technologies to precisely capture images at anatomical locations, repeatedly, and with different ultrasound transducer types were evaluated across more than five scoring criteria. Testing demonstrated two of the adapters outperformed the traditional robot gripper and manual image capture, with a compact, rotating design compatible with wireless imaging technology being most suitable for use at the point of injury. Next steps will integrate the robotic platform with computer vision and deep learning image interpretation models to automate image capture and diagnosis. This will lower the skill threshold needed for medical imaging-based triage, enabling this procedure to be available at or near the point of injury.
Published: 2024
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4. ‘The unexpected journey’: a qualitative interview study exploring patient and health professionals experiences of participating in the knee arthroplasty versus joint distraction study (KARDS)

Author: Deborah D Stocken, Roberta Longo, David Murray, David R Ellard, Howard Collier, Andrew Metcalfe, Hemant Sharma, Deborah Stocken, Hamish Simpson, Dennis McGonagle, Hemant Pandit, Susanne Arnold, Ruchi Higham, Ruben Mujica-Mota, Julie Croft, Thomas Hamilton, Bernard van Duren, Rachel Kelly, and Isabelle Smith
Subjects: Medicine
Abstract: Objective The aim of the knee arthroplasty versus joint distraction (KARDS) randomised trial was to investigate whether knee joint distraction (KJD) is non-inferior to knee arthroplasty, also known as knee replacement (KR). Here we report the findings from qualitative interviews that were part of the planned KARDS process evaluation.Design and methods Semi-structured qualitative interviews with staff and participants in secondary care. Data were analysed using thematic content analysis.Findings We were unable to complete the full-planned KARDS process evaluation as recruitment to the trial was closed early but key common themes emerged.Eleven members of staff were interviewed from two KARDS sites (eight initial interviews just after site opening and three follow-up interviews at 12 months). Eleven KARDS participants (six KR and five KJD) were interviewed. One overarching theme emerged: ‘An unexpected journey’. This incorporated subthemes including ‘an important research question’, ‘a roller coaster ride’, ‘lessons learnt’, ‘managing expectations’ and ‘a slow recovery’. These encapsulate experiences of both staff and participants.Conclusion The information that we were able to collect highlights that providing adequate and comprehensive information about all aspects of treatment including estimated timelines of recovery are essential in clinical trials of novel interventions. Incorporating a comprehensive rehabilitation package following KJD was a key learning. Process evaluations in these complex trials are essential to determine issues as early as possible so appropriate changes can be made to ensure participants have a smooth journey through the trial experience.Trial registration number ISRCTN14879004.
Published: 2024
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5. Embryonic ethanol exposure and optogenetic activation of hypocretin neurons stimulate similar behaviors early in life associated with later alcohol consumption

Author: Adam D. Collier, Nushrat Yasmin, Olga Karatayev, Abdul R. Abdulai, Boyi Yu, Milisia Fam, Samantha Campbell, and Sarah F. Leibowitz
Subjects: Medicine, Science
Abstract: Abstract The initiation of alcohol use early in life is one of the strongest predictors of developing a future alcohol use disorder. Clinical studies have identified specific behaviors during early childhood that predict an increased risk for excess alcohol consumption later in life. These behaviors, including increased hyperactivity, anxiety, novelty-seeking, exploratory behavior, impulsivity, and alcohol-seeking, are similarly stimulated in children and adolescent offspring of mothers who drink alcohol during pregnancy. Here we tested larval zebrafish in addition to young pre-weanling rats and found this repertoire of early behaviors along with the overconsumption of alcohol during adolescence to be increased by embryonic ethanol exposure. With hypocretin/orexin (Hcrt) neurons known to be stimulated by ethanol and involved in mediating these alcohol-related behaviors, we tested their function in larval zebrafish and found optogenetic activation of Hcrt neurons to stimulate these same early alcohol-related behaviors and later alcohol intake, suggesting that these neurons have an important role in producing these behaviors. Together, these results show zebrafish to be an especially useful animal model for investigating the diverse neuronal systems mediating behavioral changes at young ages that are produced by embryonic ethanol exposure and predict an increased risk for developing alcohol use disorder.
Published: 2024
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6. Minimising Adverse Drug Reactions and Verifying Economic Legitimacy-Pharmacogenomics Implementation in Children (MARVEL- PIC): protocol for a national randomised controlled trial of pharmacogenomics implementation

Author: Tim Spelman, Elizabeth Williams, Rishi S Kotecha, Rachel Conyers, Andreas Halman, Claire Moore, Tayla Stenta, Ben Felmingham, Lane Collier, Dhrita Khatri, Roxanne Dyas, Sophie Jessop, Marion K Mateos, Jesse Swen, and David A Elliott
Subjects: Medicine
Abstract: Introduction DNA-informed prescribing (termed pharmacogenomics, PGx) is the epitome of personalised medicine. Despite international guidelines existing, its implementation in paediatric oncology remains sparse.Methods and analysis Minimising Adverse Drug Reactions and Verifying Economic Legitimacy-Pharmacogenomics Implementation in Children is a national prospective, multicentre, randomised controlled trial assessing the impact of pre-emptive PGx testing for actionable PGx variants on adverse drug reaction (ADR) incidence in patients with a new cancer diagnosis or proceeding to haematopoetic stem cell transplant. All ADRs will be prospectively collected by surveys completed by parents/patients using the National Cancer Institute Pediatric Patient Reported [Ped-PRO]-Common Terminology Criteria for Adverse Events (CTCAE) (weeks 1, 6 and 12). Pharmacist will assess for causality and severity in semistructured interviews using the CTCAE and Liverpool Causality Assessment Tool. The primary outcome is a reduction in ADRs among patients with actionable PGx variants, where an ADR will be considered as any CTCAE grade 2 and above for non-haematological toxicities and any CTCAE grade 3 and above for haematological toxicities Cost-effectiveness of pre-emptive PGx (secondary outcome) will be compared with standard of care using hospital inpatient and outpatient data along with the validated Childhood Health Utility 9D Instrument. Power and statistics considerations: A sample size of 440 patients (220 per arm) will provide 80% power to detect a 24% relative risk reduction in the primary endpoint of ADRs (two-sided α=5%, 80% vs 61%), allowing for 10% drop-out.Ethics and dissemination The ethics approval of the trial has been obtained from the Royal Children’s Hospital Ethics Committee (HREC/89083/RCHM-2022). The ethics committee of each participating centres nationally has undertaken an assessment of the protocol and governance submission.Trial registration number NCT05667766.
Published: 2024
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7. Can we achieve better trial recruitment by presenting patient information through multimedia? Meta-analysis of ‘studies within a trial’ (SWATs)

Author: Vichithranie W. Madurasinghe, Peter Knapp, Sandra Eldridge, David Collier, Shaun Treweek, Jo Rick, Jonathan Graffy, Adwoa Parker, Chris Salisbury, David Torgerson, Kate Jolly, Manbinder S. Sidhu, Christopher Fife-Schaw, Mark A. Hull, Kirsty Sprange, Elizabeth Brettell, Sunil Bhandari, Alan Montgomery, and Peter Bower
Subjects: Recruitment, Information, User testing, Research methodology, Randomised controlled trial, SWATs, Medicine
Abstract: Abstract Background People need high-quality information to make decisions about research participation. Providing information in written format alone is conventional but may not be the most effective and acceptable approach. We developed a structure for the presentation of information using multimedia which included generic and trial-specific content. Our aim was to embed ‘Studies Within A Trial’ (SWATs) across multiple ongoing trials to test whether multimedia presentation of patient information led to better rates of recruitment. Methods Five trials included a SWAT and randomised their participants to receive a multimedia presentation alongside standard information, or standard written information alone. We collected data on trial recruitment, acceptance and retention and analysed the pooled results using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised following an invitation to take part. Results Five SWATs provided data on the primary outcome of proportion of participants randomised. Multimedia alongside written information results in little or no difference in recruitment rates (pooled odds ratio = 0.96, 95% CI: 0.79 to 1.17, p-value = 0.671, I 2 = 0%). There was no effect on any other outcomes. Conclusions Multimedia alongside written information did not improve trial recruitment rates. Trial registration ISRCTN71952900, ISRCTN 06710391, ISRCTN 17160087, ISRCTN05926847, ISRCTN62869767.
Published: 2023
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8. Habitat selection of Gould’s wild turkeys in southeastern Arizona

Author: Erin E. Ulrey, Patrick H. Wightman, Nicholas W. Bakner, Byron R. Buckley, Nathan Fyffe, Brittany Oleson, Alex Smallwood, James R. Heffelfinger, Michael J. Chamberlain, and Bret A. Collier
Subjects: Medicine, Science
Abstract: Abstract In semi-arid environments, resources necessary for survival may be unevenly distributed across the landscape. Gould’s wild turkeys (Meleagris gallopavo mexicana) are spatially restricted to mountainous semi-arid areas of southwestern United States and Mexico, and information on their distribution and habitat use is limited. We described how landcover type and topographical features influenced space use and habitat selection by Gould’s wild turkeys in southeastern Arizona. We used GPS data from 51 Gould’s wild turkeys to describe resource selection during 2016–2017 in southeastern Arizona, USA. We estimated home ranges and calculated resource selection functions using distance from landcover types, slope, aspect, and elevation at used locations and random locations within individual home ranges. Gould’s wild turkeys selected areas closer to pine forest and water. Likewise, Gould’s wild turkeys selected locations with moderate elevations of 1641 ± 235 m (range = 1223–2971 m), and on north and west facing slopes with a 10° ± 8.5 (range = 0.0–67.4°) incline. Our findings suggest that conserving portions of the landscape with appropriate topography and landcover types as described above will promote habitat availability for Gould’s wild turkeys.
Published: 2023
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9. The hidden pandemic: a qualitative study on how middle-aged women make sense of managing their long COVID symptoms

Author: Disa Collier and Gulcan Garip
Subjects: qualitative research, lived experience, illness experience, health seeking behaviours, misogyny, Medicine, Psychology, BF1-990
Abstract: Background A relapsing and remitting illness, long COVID can be challenging and debilitating. A person living with long COVID can feel like they are getting better and recovering only to relapse again. The aim of the research was to explore how non-hospitalized middle-aged women who contracted COVID in the first wave of the pandemic, from March 2020, are manag-ing their long COVID symptoms. Participants and procedure A qualitative research study with an interpretative phenomenological analysis approach was used to explore how the wom-en made sense of managing their condition and health seeking behaviours. Participants were recruited from long COVID Facebook groups and semi-structured interviews were conducted remotely by Teams audio; these were digitally recorded and transcribed by hand with prior informed consent. Nine women were interviewed and four themes and eight sub-themes emerged from the data. Results The four emerging themes were: inequality and inconsistent medical treatment; uncertainty and ambiguity of managing long COVID symptoms; managing other people’s expectations and perceptions of long COVID; and the changing identity. Overall, these results indicated a general mistrust in health care services to provide adequate support and individualized treatment plans leading women to self-advocacy and to seek alternative support and treatment. Conclusions This study raised questions about the possible unfair treatment of women seeking medical attention for their long COVID symptoms; how ambiguous symptoms are misattributed to anxiety and discrimination from health care professionals con-tributes towards stigma. The study concludes with recommendations for service improvement such as the compassionate validation of patients’ pain and the use of evidence-based therapeutic practices such as mindfulness.
Published: 2023
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10. Cord blood lipid correlation network profiles are associated with subsequent attention-deficit/hyperactivity disorder and autism spectrum disorder symptoms at 2 years: a prospective birth cohort studyResearch in context

Author: Kristina Vacy, Sarah Thomson, Archer Moore, Alex Eisner, Sam Tanner, Cindy Pham, Richard Saffrey, Toby Mansell, David Burgner, Fiona Collier, Peter Vuillermin, Martin O’Hely, Wah Chin Boon, Peter Meikle, Satvika Burugupalli, Anne-Louise Ponsonby, Mimi L.K. Tang, Lawrence Gray, Sarath Ranganathan, Peter Sly, Jochen Mueller, Terry Dwyerm, and John Carlin
Subjects: Lipidomics, Cord blood, Fatty acids, Acylcarnitine, Autism spectrum disorder symptoms, Attention-deficit/hyperactivity disorder symptoms, Medicine, Medicine (General), R5-920
Abstract: Summary: Background: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental conditions with early life origins. Alterations in blood lipids have been linked to ADHD and ASD; however, prospective early life data are limited. This study examined (i) associations between the cord blood lipidome and ADHD/ASD symptoms at 2 years of age, (ii) associations between prenatal and perinatal predictors of ADHD/ASD symptoms and cord blood lipidome, and (iii) mediation by the cord blood lipidome. Methods: From the Barwon Infant Study cohort (1074 mother-child pairs, 52.3% male children), child circulating lipid levels at birth were analysed using ultra-high-performance liquid chromatography-tandem mass spectrometry. These were clustered into lipid network modules via Weighted Gene Correlation Network Analysis. Associations between lipid modules and ADHD/ASD symptoms at 2 years, assessed with the Child Behavior Checklist, were explored via linear regression analyses. Mediation analysis identified indirect effects of prenatal and perinatal risk factors on ADHD/ASD symptoms through lipid modules. Findings: The acylcarnitine lipid module is associated with both ADHD and ASD symptoms at 2 years of age. Risk factors of these outcomes such as low income, Apgar score, and maternal inflammation were partly mediated by higher birth acylcarnitine levels. Other cord blood lipid profiles were also associated with ADHD and ASD symptoms. Interpretation: This study highlights that elevated cord blood birth acylcarnitine levels, either directly or as a possible marker of disrupted cell energy metabolism, are on the causal pathway of prenatal and perinatal risk factors for ADHD and ASD symptoms in early life. Funding: The foundational work and infrastructure for the BIS was sponsored by the Murdoch Children's Research Institute, Deakin University, and Barwon Health. Subsequent funding was secured from the Minderoo Foundation, the European Union's Horizon 2020 research and innovation programme (ENDpoiNTs: No 825759), National Health and Medical Research Council of Australia (NHMRC) and Agency for Science, Technology and Research Singapore [APP1149047], The William and Vera Ellen Houston Memorial Trust Fund (via HOMER Hack), The Shepherd Foundation, The Jack Brockhoff Foundation, the Scobie & Claire McKinnon Trust, the Shane O'Brien Memorial Asthma Foundation, the Our Women Our Children's Fund Raising Committee Barwon Health, the Rotary Club of Geelong, the Ilhan Food Allergy Foundation, Geelong Medical and Hospital Benefits Association, Vanguard Investments Australia Ltd, the Percy Baxter Charitable Trust, and Perpetual Trustees.
Published: 2024
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11. Legacy lessons from the COVID-19 era to improve trial participation and retention: Views from trial participants, PPIE contributors and trial staff across the NIHR portfolio.

Author: Heather Leggett, Karen Vinall-Collier, Julia Csikar, Sophy Barber, Rachel Carr, Amrit Bhatti, and Sue Pavitt
Subjects: Medicine, Science
Abstract: BackgroundThe Covid-19 pandemic had a profound effect on the delivery of healthcare research. Covid-19 research was prioritised and many non-essential trials were paused. This study explores the engagement experiences of trial participants', PPIE contributors' and trial staff during the Covid-19 pandemic and towards recovery and restoring a diverse and balanced UK clinical trials portfolio.MethodsInterviews and focus groups were undertaken with PPIE contributors, trial participants and trial staff members from NIHR research trials across the UK (November 2020-June 2021) across portfolio specialities: Cancer, Oral and Dental Health, Musculoskeletal Disorders, Cardiovascular Disease, Neurological Disorders, Primary Care, and Conditions associated with susceptibility to Covid-19 (Diabetes, Stroke, Respiratory Disorders). Topic guides were developed for each participant group and interviews were conducted over Zoom. The transcripts were analysed using codebook thematic analysis in NVivo (V.12).Results106 participants comprising, 45 PPIE contributors, 27 trial participants and 34 trial staff members were recruited. Three themes to engagement with trials during Covid-19 were developed. 1) Ensuring continued contact. Continued and tailored communication, having a trial point of contact and regular updates all enhanced trial engagement and retention. Patients' unfamiliarity with materials being sent electronically reduced engagement and trust. 2) A balanced move to remote consultations. Remote follow-up and monitoring were convenient and allowed for wider recruitment across the UK. Participants were more likely to discuss personal subjects in their own homes. Remote visits lacked a personal touch, some concerns over missed diagnoses or being unable to appreciate the situation, technical abilities or equipment failures were seen as barriers, especially for disadvantaged or older people. 3) The importance of feeling fully informed. Factors that supported attendance were knowledge about trial conduct adherence to Covid-19 regulations, social distancing, clear signage at the site and opportunities to ask questions. Barriers included not knowing what to expect and not feeling safe with rules and regulations.ConclusionsOur findings highlight a number of ways to future proof trial delivery against future pandemics or disruptions such as offering online options to participate in research, ensuring consistent communication between participants and the research team, making sure participants feel fully informed and the continued reassurance of safety in the clinical setting.
Published: 2024
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12. Trends in harmful drug exposure during pregnancy in France between 2013 and 2019: A nationwide cohort study.

Author: Margaux Louchet, Mathis Collier, Nathanaël Beeker, Laurent Mandelbrot, Jeanne Sibiude, Laurent Chouchana, and Jean Marc Treluyer
Subjects: Medicine, Science
Abstract: ObjectiveDescribe the trends of exposure to harmful drugs during pregnancy over recent years in France.DesignNationwide cohort study.SettingThe French National administrative health Data System (SNDS).PopulationPregnancies starting between 2013 and 2019 and outcomes corresponding to live births, medical terminations of pregnancy, and stillbirths.MethodsEach pregnancy was divided into a preconceptional period of 90 days before conception and three trimesters from conception to birth. Harmful drugs were defined according to their risks to the fetus: teratogenicity or fetotoxicity. Exposure was defined using the critical period during pregnancy for each type of harmful drug: preconceptional period or first trimester for teratogenic drugs and second or third trimesters for fetotoxic drugs.Main outcome measuresPrevalence of pregnancies exposed to at least one harmful drug.ResultsAmong 5,253,284 pregnancies, 204,402 (389 per 10,000) pregnancies were exposed to at least one harmful drug during the critical periods: 48,326 (92 per 10,000) pregnancies were exposed to teratogenic drugs during the preconceptional period or the first trimester, and 155,514 (299 per 10,000) pregnancies were exposed to fetotoxic drugs during the second or third trimesters. Teratogenic drugs were mainly retinoids for topical use (44 per 10,000 pregnancies), antiepileptics (13 per 10,000 pregnancies) and statins (13 per 10,000 pregnancies). Fetotoxic drugs were mainly non-steroidal anti-inflammatory drugs (NSAIDs), for systemic (128 per 10,000 pregnancies) and topical use (122 per 10,000 pregnancies). Exposure to teratogenic drugs decreased from the preconceptional period to the first trimester. Exposure to fetotoxic drugs decreased from the second to the third trimester. Between 2013 and 2019, we found a decrease in harmful drug exposure overall, mainly for topical and systemic NSAIDs and for topical retinoids.ConclusionsIn this nationwide study, about one in 25 pregnancies was exposed to at least one harmful drug, mainly NSAIDs and topical retinoids. Although the prevalence of harmful drug exposure decreased over the study period, NSAID exposure in the second and third trimester remains of concern.
Published: 2024
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13. Impact of the COVID-19 pandemic on routine surveillance for adults with chronic hepatitis B virus (HBV) infection in the UK [version 2; peer review: 2 approved]

Author: Eleni Nastouli, Eleanor Barnes, Graham S. Cooke, Cori Campbell, Theresa Noble, David A. Smith, Steve Harris, Kinga A Várnai, Gail Roadknight, Hizni Salih, Ben Glampson, Stephanie Little, Dimitri Papadimitriou, Paul Klenerman, Luca Mercuri, Vince Taylor, Christopher R Jones, Hang Phan, Afzal Chaudhry, Josune Olza, Florina Borca, Luis Romão, Frazer Warricker, Louise English, David Ramlakhan, Monique I. Andersson, Salim I. Khakoo, Jane Collier, Philippa C. Matthews, Kerrie Woods, William Gelson, Tingyan Wang, Oliver Freeman, and Jim Davies
Subjects: hepatitis B virus, HBV, epidemiology, virology, viral hepatitis, COVID-19, eng, Medicine, Science
Abstract: Background To determine the impact of the COVID-19 pandemic on the population with chronic Hepatitis B virus (HBV) infection under hospital follow-up in the UK, we quantified the coverage and frequency of measurements of biomarkers used for routine surveillance (alanine transferase [ALT] and HBV viral load). Methods We used anonymized electronic health record data from the National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) pipeline representing five UK National Health Service (NHS) Trusts. Results We report significant reductions in surveillance of both biomarkers during the pandemic compared to pre-COVID-19 years, both in terms of the proportion of patients who had ≥1 measurement annually, and the mean number of measurements per patient. Conclusions These results demonstrate the real-time utility of HIC data in monitoring health-care provision, and support interventions to provide catch-up services to minimise the impact of the pandemic. Further investigation is required to determine whether these disruptions will be associated with increased rates of adverse chronic HBV outcomes.
Published: 2023
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14. Motivating change in resident language use through narrative medicine workshops

Author: Kristin Collier, Amit Gupta, and Alexandra Vinson
Subjects: Narrative medicine, Doctor-patient communication, Medical training, Special aspects of education, LC8-6691, Medicine
Abstract: Abstract Background There are many ways that students and trainees learn to talk about patients. The way trainees and physicians use language during clinical care is important, as labeling patients can have adverse effects on patient safety. Communication is considered a core competency by The Accreditation Council on Graduate Medical Education (ACGME). Past research has shown that participants in narrative medicine curricula report developing stronger communication skills however it is not clear how these workshops motivated trainees to use language differently during patient care. To explore this, we interviewed second-year residents in academic year 19–20 about their experiences both in participating in narrative medicine workshops and giving patient care. Methods The framing context for this constructivist thematic analysis is a series of narrative medicine workshops facilitated for interns in an internal medicine residency program at a large academic medical center during the 18–19 academic year. We developed a semi-structured interview study that allowed residents to reflect on their experiences in these workshops. Eighteen out of 60 residents (30%) were interviewed. Results We found that sessions regarding language use in patient care shaped how interns thought about and used language during clinical work, a finding that arose spontaneously during interviews. Conclusions Our research suggests that workshops aimed specifically at addressing the use of language in healthcare can have meaningful impact on trainees. Our study makes a unique contribution to the scholarship by suggesting that training in narrative medicine can lead to a change in the way that trainees use language during their clinical work.
Published: 2022
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15. A plastic and reconstructive surgery landscape assessment of Malawi: a scoping review of Malawian literature

Author: Chifundo Msokera, Meredith Xepoleas, Zachary J. Collier, Priyanka Naidu, and William Magee
Subjects: Malawi, Plastic surgery, Reconstructive surgical procedures, Burns, Medicine
Abstract: Abstract Background Plastic and reconstructive surgery (PRS) remains highly relevant to the unmet need for surgery in Malawi. Better understanding the current PRS landscape and its barriers may help address some of these challenges. This scoping review aimed to describe: (1) the scope and focus of the PRS literature being produced in Malawi and (2) the challenges, deficits, and barriers to providing accessible, high-quality PRS in Malawi. Methods This scoping review was conducted on four databases (SCOPUS, PubMed, Web of Science, EMBASE) from inception through September 1, 2020 following the PRISMA-ScR guidelines. Results The database search retrieved 3852 articles, of which 31 were included that examined the burden of PRS-related conditions in Malawi. Of these 31 articles, 25 primarily discussed burn-related care. Burns injuries have a high mortality rate; between 27 and 75% in the studies. The literature revealed that there are only two burn units nationally with one PRS specialist in each unit, compounded by a lack of interest in PRS specialization by Malawian medical students. Congenital anomalies were the only other PRS-related condition examined and reported in the literature, accounting for 23% of all pediatric surgeries in tertiary facilities. Conclusions There is a need to increase the country's capacity to handle burn reconstruction and other PRS-related conditions to reduce overall morbidity and mortality. Additional publicly funded research at the district and community level is warranted to determine the true burden of PRS disease in Malawi to derive health system strengthening and workforce capacity building strategies.
Published: 2022
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16. Monitoring of SARS-CoV-2 antibodies using dried blood spot for at-home collection

Author: Peyton K. Miesse, Bradley B. Collier, and Russell P. Grant
Subjects: Medicine, Science
Abstract: Abstract The utilization of vaccines to fight the spread of SARS-CoV-2 has led to a growing need for expansive serological testing. To address this, an EUA approved immunoassay for detection of antibodies to SARS-CoV-2 in venous serum samples was investigated for use with dried blood spot (DBS) samples. Results from self-collected DBS samples demonstrated a 98.1% categorical agreement to venous serum with a correlation (R) of 0.9600 while professionally collected DBS samples demonstrated a categorical agreement of 100.0% with a correlation of 0.9888 to venous serum. Additional studies were performed to stress different aspects of at-home DBS collection, including shipping stability, effects of interferences, and other sample-specific robustness studies. These studies demonstrated a categorical agreement of at least 95.0% and a mean bias less than ± 20.0%. Furthermore, the ability to track antibody levels following vaccination with the BioNTech/Pfizer vaccine was demonstrated with serial self-collected DBS samples from pre-dose (Day 0) out to 19 weeks.
Published: 2022
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17. Point of care SARS-CoV-2 nucleic acid testing in schools improves school attendance [version 2; peer review: 2 approved]

Author: Dami A. Collier, Effrossyni Gkrania-Klotsas, Rachel Bousfield, and Ravindra K. Gupta
Subjects: SARS-CoV-2, school, testing, rapid, point of care, eng, Medicine, Science
Abstract: Background: National lockdowns have led to significant interruption to children’s education globally. In the Autumn term in 2020, school absence in England and Wales was almost five times higher than the same period in 2019. Transmission of SARS-CoV-2 in schools and ongoing interruption to education remains a concern. However, evaluation of rapid point of care (POC) polymerase chain reaction (PCR) testing in British schools has not been undertaken. Methods: This is a survey of secondary schools in England that implemented PCR-based rapid POC testing. The study aims to measure the prevalence of SARS-CoV-2 infection in schools, to assess the impact of this testing on school attendance and closures, and to describe schools experiences with testing. All schools utilised the SAMBA II SARS-CoV-2 testing platform. Results: 12 fee-paying secondary schools in England were included. Between September 1st 2020 and December 16th 2020, 697 on site rapid POC PCR tests were performed and 6.7% of these were positive for SARS-CoV-2 infection. There were five outbreaks in three schools during this time which were contained. Seven groups of close contacts within the school known as bubbles had to quarantine but there were no school closures. 84% of those tested were absent from school for less than one day whilst awaiting their test result. This potentially saved between 1047 and 1570 days off school in those testing negative compared to the NHS PCR laboratory test. Schools reported a positive impact of having a rapid testing platform as it allowed them to function as fully as possible during this pandemic. Conclusions: Rapid POC PCR testing platforms should be widely available and utilised in school settings. Reliable positive tests will prevent outbreaks and uncontrolled spread of infection within school settings. Reliable negative test results will reassure students, parents and staff and prevent disruption to education.
Published: 2022
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18. DNA passes through cohesin’s hinge as well as its Smc3–kleisin interface

Author: James E Collier and Kim A Nasmyth
Subjects: cohesin, condensin, SMC, Medicine, Science, Biology (General), QH301-705.5
Abstract: The ring model proposes that sister chromatid cohesion is mediated by co-entrapment of sister DNAs inside a single tripartite cohesin ring. The model explains how Scc1 cleavage triggers anaphase but has hitherto only been rigorously tested using small circular mini-chromosomes in yeast, where covalently circularizing the ring by crosslinking its three interfaces induces catenation of individual and sister DNAs. If the model applies to real chromatids, then the ring must have a DNA entry gate essential for mitosis. Whether this is situated at the Smc3/Scc1 or Smc1/Smc3 hinge interface is an open question. We have previously demonstrated DNA entrapment by cohesin in vitro (Collier et al., 2020). Here we show that cohesin in fact possesses two DNA gates, one at the Smc3/Scc1 interface and a second at the Smc1/3 hinge. Unlike the Smc3/Scc1 interface, passage of DNAs through SMC hinges depends on both Scc2 and Scc3, a pair of regulatory subunits necessary for entrapment in vivo. This property together with the lethality caused by locking this interface but not that between Smc3 and Scc1 in vivo suggests that passage of DNAs through the hinge is essential for building sister chromatid cohesion. Passage of DNAs through the Smc3/Scc1 interface is necessary for cohesin’s separase-independent release from chromosomes and may therefore largely serve as an exit gate.
Published: 2022
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19. Global influenza surveillance systems to detect the spread of influenza-negative influenza-like illness during the COVID-19 pandemic: Time series outlier analyses from 2015-2020.

Author: Natalie L Cobb, Sigrid Collier, Engi F Attia, Orvalho Augusto, T Eoin West, and Bradley H Wagenaar
Subjects: Medicine
Abstract: BackgroundSurveillance systems are important in detecting changes in disease patterns and can act as early warning systems for emerging disease outbreaks. We hypothesized that analysis of data from existing global influenza surveillance networks early in the COVID-19 pandemic could identify outliers in influenza-negative influenza-like illness (ILI). We used data-driven methods to detect outliers in ILI that preceded the first reported peaks of COVID-19.Methods and findingsWe used data from the World Health Organization's Global Influenza Surveillance and Response System to evaluate time series outliers in influenza-negative ILI. Using automated autoregressive integrated moving average (ARIMA) time series outlier detection models and baseline influenza-negative ILI training data from 2015-2019, we analyzed 8,792 country-weeks across 28 countries to identify the first week in 2020 with a positive outlier in influenza-negative ILI. We present the difference in weeks between identified outliers and the first reported COVID-19 peaks in these 28 countries with high levels of data completeness for influenza surveillance data and the highest number of reported COVID-19 cases globally in 2020. To account for missing data, we also performed a sensitivity analysis using linear interpolation for missing observations of influenza-negative ILI. In 16 of the 28 countries (57%) included in this study, we identified positive outliers in cases of influenza-negative ILI that predated the first reported COVID-19 peak in each country; the average lag between the first positive ILI outlier and the reported COVID-19 peak was 13.3 weeks (standard deviation 6.8). In our primary analysis, the earliest outliers occurred during the week of January 13, 2020, in Peru, the Philippines, Poland, and Spain. Using linear interpolation for missing data, the earliest outliers were detected during the weeks beginning December 30, 2019, and January 20, 2020, in Poland and Peru, respectively. This contrasts with the reported COVID-19 peaks, which occurred on April 6 in Poland and June 1 in Peru. In many low- and middle-income countries in particular, the lag between detected outliers and COVID-19 peaks exceeded 12 weeks. These outliers may represent undetected spread of SARS-CoV-2, although a limitation of this study is that we could not evaluate SARS-CoV-2 positivity.ConclusionsUsing an automated system of influenza-negative ILI outlier monitoring may have informed countries of the spread of COVID-19 more than 13 weeks before the first reported COVID-19 peaks. This proof-of-concept paper suggests that a system of influenza-negative ILI outlier monitoring could have informed national and global responses to SARS-CoV-2 during the rapid spread of this novel pathogen in early 2020.
Published: 2022
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20. Early life infection and proinflammatory, atherogenic metabolomic and lipidomic profiles in infancy: a population-based cohort study

Author: Toby Mansell, Richard Saffery, Satvika Burugupalli, Anne-Louise Ponsonby, Mimi LK Tang, Martin O'Hely, Siroon Bekkering, Adam Alexander T Smith, Rebecca Rowland, Sarath Ranganathan, Peter D Sly, Peter Vuillermin, Fiona Collier, Peter Meikle, David Burgner, and Barwon Infant Study Investigator Group
Subjects: inflammation, metabolomic, lipidomic, infection, paediatric, Barwon Infant Study, Medicine, Science, Biology (General), QH301-705.5
Abstract: Background: The risk of adult onset cardiovascular and metabolic (cardiometabolic) disease accrues from early life. Infection is ubiquitous in infancy and induces inflammation, a key cardiometabolic risk factor, but the relationship between infection, inflammation, and metabolic profiles in early childhood remains unexplored. We investigated relationships between infection and plasma metabolomic and lipidomic profiles at age 6 and 12 months, and mediation of these associations by inflammation. Methods: Matched infection, metabolomics, and lipidomics data were generated from 555 infants in a pre-birth longitudinal cohort. Infection data from birth to 12 months were parent-reported (total infections at age 1, 3, 6, 9, and 12 months), inflammation markers (high-sensitivity C-reactive protein [hsCRP]; glycoprotein acetyls [GlycA]) were quantified at 12 months. Metabolic profiles were 12-month plasma nuclear magnetic resonance metabolomics (228 metabolites) and liquid chromatography/mass spectrometry lipidomics (776 lipids). Associations were evaluated with multivariable linear regression models. In secondary analyses, corresponding inflammation and metabolic data from birth (serum) and 6-month (plasma) time points were used. Results: At 12 months, more frequent infant infections were associated with adverse metabolomic (elevated inflammation markers, triglycerides and phenylalanine, and lower high-density lipoprotein [HDL] cholesterol and apolipoprotein A1) and lipidomic profiles (elevated phosphatidylethanolamines and lower trihexosylceramides, dehydrocholesteryl esters, and plasmalogens). Similar, more marked, profiles were observed with higher GlycA, but not hsCRP. GlycA mediated a substantial proportion of the relationship between infection and metabolome/lipidome, with hsCRP generally mediating a lower proportion. Analogous relationships were observed between infection and 6-month inflammation, HDL cholesterol, and apolipoprotein A1. Conclusions: Infants with a greater infection burden in the first year of life had proinflammatory and proatherogenic plasma metabolomic/lipidomic profiles at 12 months of age that in adults are indicative of heightened risk of cardiovascular disease, obesity, and type 2 diabetes. These findings suggest potentially modifiable pathways linking early life infection and inflammation with subsequent cardiometabolic risk. Funding: The establishment work and infrastructure for the BIS was provided by the Murdoch Children’s Research Institute (MCRI), Deakin University, and Barwon Health. Subsequent funding was secured from National Health and Medical Research Council of Australia (NHMRC), The Shepherd Foundation, The Jack Brockhoff Foundation, the Scobie & Claire McKinnon Trust, the Shane O’Brien Memorial Asthma Foundation, the Our Women’s Our Children’s Fund Raising Committee Barwon Health, the Rotary Club of Geelong, the Minderoo Foundation, the Ilhan Food Allergy Foundation, GMHBA, Vanguard Investments Australia Ltd, and the Percy Baxter Charitable Trust, Perpetual Trustees. In-kind support was provided by the Cotton On Foundation and CreativeForce. The study sponsors were not involved in the collection, analysis, and interpretation of data; writing of the report; or the decision to submit the report for publication. Research at MCRI is supported by the Victorian Government’s Operational Infrastructure Support Program. This work was also supported by NHMRC Senior Research Fellowships to ALP (1008396); DB (1064629); and RS (1045161) , NHMRC Investigator Grants to ALP (1110200) and DB (1175744), NHMRC-A*STAR project grant (1149047). TM is supported by an MCRI ECR Fellowship. SB is supported by the Dutch Research Council (452173113).
Published: 2022
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21. Ontogeny of circulating lipid metabolism in pregnancy and early childhood – a longitudinal population study

Author: Satvika Burugupalli, Adam Alexander T Smith, Gavriel Oshlensky, Kevin Huynh, Corey Giles, Tingting Wang, Alexandra George, Sudip Paul, Anh Nguyen, Thy Duong, Natalie Mellett, Michelle Cinel, Sartaj Ahmad Mir, Li Chen, Markus R Wenk, Neerja Karnani, Fiona Collier, Richard Saffery, Peter Vuillermin, Anne-Louise Ponsonby, David Burgner, Peter Meikle, and Barwon Infant Study Investigator team
Subjects: newborn, infants, early childhood, Medicine, Science, Biology (General), QH301-705.5
Abstract: Background: There is mounting evidence that in utero and early life exposures may predispose an individual to metabolic disorders in later life; and dysregulation of lipid metabolism is critical in such outcomes. However, there is limited knowledge about lipid metabolism and factors causing lipid dysregulation in early life that could result in adverse health outcomes in later life. We studied the effect of antenatal factors such as gestational age, birth weight, and mode of birth on lipid metabolism at birth; changes in the circulating lipidome in the first 4 years of life and the effect of breastfeeding in the first year of life. From this study, we aim to generate a framework for deeper understanding into factors effecting lipid metabolism in early life, to provide early interventions for those at risk of developing metabolic disorders including cardiovascular diseases. Methods: We performed comprehensive lipid profiling of 1074 mother-child dyads in the Barwon Infant Study (BIS), a population-based pre-birth cohort and measured 776 distinct lipid features across 39 lipid classes using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). We measured lipids in 1032 maternal serum samples at 28 weeks’ gestation, 893 cord serum samples at birth, 793, 735, and 511 plasma samples at 6, 12 months, and 4 years, respectively. Cord serum was enriched with long chain poly-unsaturated fatty acids (LC-PUFAs), and corresponding cholesteryl esters relative to the maternal serum. We performed regression analyses to investigate the associations of cord serum lipid species with antenatal factors: gestational age, birth weight, mode of birth and duration of labour. Results: The lipidome differed between mother and newborn and changed markedly with increasing child’s age. Alkenylphosphatidylethanolamine species containing LC-PUFAs increased with child’s age, whereas the corresponding lysophospholipids and triglycerides decreased. Majority of the cord serum lipids were strongly associated with gestational age and birth weight, with most lipids showing opposing associations. Each mode of birth showed an independent association with cord serum lipids. Breastfeeding had a significant impact on the plasma lipidome in the first year of life, with up to 17-fold increases in a few species of alkyldiaclylglycerols at 6 months of age. Conclusions: This study sheds light on lipid metabolism in infancy and early childhood and provide a framework to define the relationship between lipid metabolism and health outcomes in early childhood. Funding: This work was supported by the A*STAR-NHMRC joint call funding (1711624031).
Published: 2022
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22. Understanding the burden of interstitial lung disease post-COVID-19: the UK Interstitial Lung Disease-Long COVID Study (UKILD-Long COVID)

Author: R Gisli Jenkins, A John Simpson, Jennifer K Quint, Nicholas D Weatherley, Guilhem Collier, Jim M Wild, David R Thickett, Shaney L Barratt, Puja Mehta, Nazia Chaudhuri, Ling-Pei Ho, Lisa G Spencer, John F Blaikley, Fasihul Khan, Iain Stewart, John Kenneth Baillie, Rod Lawson, Simon R Johnson, Paul Beirne, Mark Spears, Laura Fabbri, Joseph Jacob, Fergus V Gleeson, Mark G Jones, Bibek Gooptu, Rachel C Chambers, Philip L Molyneaux, Peter M George, Michael A Gibbons, Emma K Denneny, Melissa Heightman, Toby E Hillman, Joanna C Porter, Manuela Platé, Stephen M Bianchi, Chris E Brightling, Richard James Allen, Annemarie Docherty, Jane A Mitchell, Ian P Hall, Jonathan Brooke, Louise V Wain, Malcolm Semple, Raminder Aul, Neil A Hanley, Krisnah Poinasamy, Pilar Rivera-Ortega, DJF Smith, Stefan C Stanel, A A Roger Thompson, Simon LF Walsh, Mark Everard Weeks, Dan G Wootton, and Karen Piper Hanley
Subjects: Medicine, Diseases of the respiratory system, RC705-779
Abstract: Introduction The COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not. Early data suggest potentially severe long-term consequence of COVID-19 is development of long COVID-19-related interstitial lung disease (LC-ILD).Methods and analysis The UK Interstitial Lung Disease Consortium (UKILD) will undertake longitudinal observational studies of patients with suspected ILD following COVID-19. The primary objective is to determine ILD prevalence at 12 months following infection and whether clinically severe infection correlates with severity of ILD. Secondary objectives will determine the clinical, genetic, epigenetic and biochemical factors that determine the trajectory of recovery or progression of ILD. Data will be obtained through linkage to the Post-Hospitalisation COVID platform study and community studies. Additional substudies will conduct deep phenotyping. The Xenon MRI investigation of Alveolar dysfunction Substudy will conduct longitudinal xenon alveolar gas transfer and proton perfusion MRI. The POST COVID-19 interstitial lung DiseasE substudy will conduct clinically indicated bronchoalveolar lavage with matched whole blood sampling. Assessments include exploratory single cell RNA and lung microbiomics analysis, gene expression and epigenetic assessment.Ethics and dissemination All contributing studies have been granted appropriate ethical approvals. Results from this study will be disseminated through peer-reviewed journals.Conclusion This study will ensure the extent and consequences of LC-ILD are established and enable strategies to mitigate progression of LC-ILD.
Published: 2021
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23. Aggregation in the spotlight

Author: Zihao Wang, Miranda Collier, and Justin Benesch
Subjects: molecular condensates, RRM, chaperones, time-resolved quantitative XL-MS, FUS, aging, Medicine, Science, Biology (General), QH301-705.5
Abstract: New findings clarify apparently conflicting results about how molecular agents that preserve protein integrity prevent harmful, dense aggregates from forming.
Published: 2021
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24. TGFβ signalling is required to maintain pluripotency of human naïve pluripotent stem cells

Author: Anna Osnato, Stephanie Brown, Christel Krueger, Simon Andrews, Amanda J Collier, Shota Nakanoh, Mariana Quiroga Londoño, Brandon T Wesley, Daniele Muraro, A Sophie Brumm, Kathy K Niakan, Ludovic Vallier, Daniel Ortmann, and Peter J Rugg-Gunn
Subjects: pluripotent stem cells, embryonic stem cells, gene regulation, Medicine, Science, Biology (General), QH301-705.5
Abstract: The signalling pathways that maintain primed human pluripotent stem cells (hPSCs) have been well characterised, revealing a critical role for TGFβ/Activin/Nodal signalling. In contrast, the signalling requirements of naïve human pluripotency have not been fully established. Here, we demonstrate that TGFβ signalling is required to maintain naïve hPSCs. The downstream effector proteins – SMAD2/3 – bind common sites in naïve and primed hPSCs, including shared pluripotency genes. In naïve hPSCs, SMAD2/3 additionally bind to active regulatory regions near to naïve pluripotency genes. Inhibiting TGFβ signalling in naïve hPSCs causes the downregulation of SMAD2/3-target genes and pluripotency exit. Single-cell analyses reveal that naïve and primed hPSCs follow different transcriptional trajectories after inhibition of TGFβ signalling. Primed hPSCs differentiate into neuroectoderm cells, whereas naïve hPSCs transition into trophectoderm. These results establish that there is a continuum for TGFβ pathway function in human pluripotency spanning a developmental window from naïve to primed states.
Published: 2021
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25. Psychological distress and trauma in doctors providing frontline care during the COVID-19 pandemic in the United Kingdom and Ireland: a prospective longitudinal survey cohort study

Author: Daniel Horner, Jo Daniels, Charles Reynard, James Foley, Blair Graham, Mark David Lyttle, M Anderson, J Browning, M Clark, S Foster, S Hartshorn, M Jacobs, S Messahel, N Mullen, J Brown, Michael Barrett, S Subramaniam, S Williams, A Ahmed, E Williams, S Hall, Edward Carlton, C Bi, M Khan, R Hannah, S Taylor, L Dunlop, J Gumley, K Knight, C Williams, J Turner, B Taylor, R Mills, M Lim, J Evans, C O’Connell, Tom Roberts, A Rai, P Singh, M Williams, S Graham, Etimbuk Umana, R Taylor, S Rahman, J Wright, J Lynch, S Lewis, P Fitzpatrick, J Ng, V Talwar, N Ali, G Pells, P Ellis, J Bailey, John Cronin, J Morgan, K Samuel, A Ali, M Patel, R Evans, S Morgan, A Hill, S Rao, S Currie, C Thomas, K Thomas, William Hulme, Katie Samuel, Robert Hirst, H Cooper, L McKechnie, S Pradhan, A Brookes, W Niven, L Kane, C Rimmer, K Kaur, R Stewart, T Hussan, P Cuthbert, M Alex, F Barham, R Macfarlane, M Jee Poh Hock, C Ward, C Weegenaar, O Williams, S Manou, MH Elwan, C Nunn, C Reynard, L How, D McConnell, J Muller, H Malik, K Challen, C Magee, S Pintus, S Langston, C Szekeres, L Kehler, C Leech, Y Moulds, A Mackay, R Wright, A Saunders, S Naeem, N Cherian, C Boulind, L Brown, E Grocholski, A Tabner, M Colmar, D Raffo, L Somerset, C Holmes, L Armstrong, S Collins, J Lowe, J Ritchie, F Wood, M Mohammad, S Wilson, R O'Sullivan, R Ellis, M MacKenzie, B Johnson, R Das, L Robinson, P Turton, L Robertson, A Robertson, J Hunt, João Vinagre, H Millar, R Freeman, A Corfield, R McQuillan, A Hormis, L Mackenzie, S Sharma Hajela, J Phizacklea, J Maney, K Malik, D Metcalfe, N Mathai, S Timmis, A Sattout, R Newport, E Fadden, D Bawden, B O'Hare, C Roe, D Bewick, F Taylor, L Barnicott, A Charlton, L McCrae, C Munday, E Godden, A Turner, R Sainsbury, A Lawrence-Ball, R House, S Patil, I Skene, M Winstanley, N Tambe, D Mawhinney, M Elkanzi, T Perry, W Kan, M Cheema, A Clarey, R Greenhalgh, A Gulati, S Marimuthu, K Webster, A Howson, R Doonan, B Shrestha, L Stanley, A Trimble, E Colley, J Lockwood, T Mohamed, H Jarman, S Ramraj, V Worsnop, N Masood, R McLatchie, A Peasley, S Bongale, U Bait, S Nagendran, A Hay, F Mendes, H Raybould, T Baron, C Ponmani, M Depante, R Sneep, Z Al-Janabi, A Rainey, N Marriage, B Mallon, J McLaren, S Hart, M Elsheikh, L Cocker, S Keers, K L Vincent, D Craver, N Sarja, N Moultrie, M Viegas, S Purvis, E Wooffinden, C Davies, S Foreman, A Da-Costa, C Ngua, S Duckitt, N Hoskins, J Fryer, T Hine, F Ihsan, L Frost, H Abdullah, K Bader, K Gray, M Manoharan, R Muswell, P Amiri, M Bonsano, S Shrivastava, F Raza, E Christmas, M Riyat, L O'Rourke, H Knott, K Adeboye, M Ramazany, K Iftikhar, N Abela, R Darke, D Maasdorp, H Murphy, H Edmundson, c Orjioke, L Harwood, D Worley, K Lines, W Collier, J Everson, D Ranasinghe, N Maleki, A Stafford, S Gokani, M Charalambos, A Olajide, H Ahmad, K Holzman, A Patton, S Gilmartin, S Uí Bhroin, S Kukaswadia, C Prendergast, C Dalla Vecchia, M Grummell, I Grossi, B MacManus, A Boyle, A Waite, J Vinagre, D George, C Battle, J Anandarajah, I Hancock, D Manthalapo, Ramesh Babu, FM Burton, I Musliam, Veettil Asif, and M JeePoh Hock
Subjects: Medicine
Abstract: Objectives The psychological impact of the COVID-19 pandemic on doctors is a significant concern. Due to the emergence of multiple pandemic waves, longitudinal data on the impact of COVID-19 are vital to ensure an adequate psychological care response. The primary aim was to assess the prevalence and degree of psychological distress and trauma in frontline doctors during the acceleration, peak and deceleration of the COVID-19 first wave. Personal and professional factors associated with psychological distress are also reported.Design A prospective online three-part longitudinal survey.Setting Acute hospitals in the UK and Ireland.Participants Frontline doctors working in emergency medicine, anaesthetics and intensive care medicine during the first wave of the COVID-19 pandemic in March 2020.Primary outcome measures Psychological distress and trauma measured using the General Health Questionnaire-12 and the Impact of Events-Revised.Results The initial acceleration survey distributed across networks generated a sample of 5440 doctors. Peak and deceleration response rates from the original sample were 71.6% (n=3896) and 56.6% (n=3079), respectively. Prevalence of psychological distress was 44.7% (n=1334) during the acceleration, 36.9% (n=1098) at peak and 31.5% (n=918) at the deceleration phase. The prevalence of trauma was 23.7% (n=647) at peak and 17.7% (n=484) at deceleration. The prevalence of probable post-traumatic stress disorder was 12.6% (n=343) at peak and 10.1% (n=276) at deceleration. Worry of family infection due to clinical work was the factor most strongly associated with both distress (R2=0.06) and trauma (R2=0.10).Conclusion Findings reflect a pattern of elevated distress at acceleration and peak, with some natural recovery. It is essential that policymakers seek to prevent future adverse effects through (a) provision of vital equipment to mitigate physical and psychological harm, (b) increased awareness and recognition of signs of psychological distress and (c) the development of clear pathways to effective psychological care.Trial registration number ISRCTN10666798.
Published: 2021
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26. Folding of cohesin’s coiled coil is important for Scc2/4-induced association with chromosomes

Author: Naomi J Petela, Andres Gonzalez Llamazares, Sarah Dixon, Bin Hu, Byung-Gil Lee, Jean Metson, Heekyo Seo, Antonio Ferrer-Harding, Menelaos Voulgaris, Thomas Gligoris, James Collier, Byung-Ha Oh, Jan Löwe, and Kim A Nasmyth
Subjects: sister chromatid cohesion, folding, cryo-em, Medicine, Science, Biology (General), QH301-705.5
Abstract: Cohesin’s association with and translocation along chromosomal DNAs depend on an ATP hydrolysis cycle driving the association and subsequent release of DNA. This involves DNA being ‘clamped’ by Scc2 and ATP-dependent engagement of cohesin’s Smc1 and Smc3 head domains. Scc2’s replacement by Pds5 abrogates cohesin’s ATPase and has an important role in halting DNA loop extrusion. The ATPase domains of all SMC proteins are separated from their hinge dimerisation domains by 50-nm-long coiled coils, which have been observed to zip up along their entire length and fold around an elbow, thereby greatly shortening the distance between hinges and ATPase heads. Whether folding exists in vivo or has any physiological importance is not known. We present here a cryo-EM structure of the apo form of cohesin that reveals the structure of folded and zipped-up coils in unprecedented detail and shows that Scc2 can associate with Smc1’s ATPase head even when it is fully disengaged from that of Smc3. Using cysteine-specific crosslinking, we show that cohesin’s coiled coils are frequently folded in vivo, including when cohesin holds sister chromatids together. Moreover, we describe a mutation (SMC1D588Y) within Smc1’s hinge that alters how Scc2 and Pds5 interact with Smc1’s hinge and that enables Scc2 to support loading in the absence of its normal partner Scc4. The mutant phenotype of loading without Scc4 is only explicable if loading depends on an association between Scc2/4 and cohesin’s hinge, which in turn requires coiled coil folding.
Published: 2021
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27. In vitro reconstitution reveals major differences between human and bacterial cytochrome c synthases

Author: Molly C Sutherland, Deanna L Mendez, Shalon E Babbitt, Dustin E Tillman, Olga Melnikov, Nathan L Tran, Noah T Prizant, Andrea L Collier, and Robert G Kranz
Subjects: Heme, cytochrome c, synthases, heme attachment, cytochrome c biogenesis, post translational modification, Medicine, Science, Biology (General), QH301-705.5
Abstract: Cytochromes c are ubiquitous heme proteins in mitochondria and bacteria, all possessing a CXXCH (CysXxxXxxCysHis) motif with covalently attached heme. We describe the first in vitro reconstitution of cytochrome c biogenesis using purified mitochondrial (HCCS) and bacterial (CcsBA) cytochrome c synthases. We employ apocytochrome c and peptide analogs containing CXXCH as substrates, examining recognition determinants, thioether attachment, and subsequent release and folding of cytochrome c. Peptide analogs reveal very different recognition requirements between HCCS and CcsBA. For HCCS, a minimal 16-mer peptide is required, comprised of CXXCH and adjacent alpha helix 1, yet neither thiol is critical for recognition. For bacterial CcsBA, both thiols and histidine are required, but not alpha helix 1. Heme attached peptide analogs are not released from the HCCS active site; thus, folding is important in the release mechanism. Peptide analogs behave as inhibitors of cytochrome c biogenesis, paving the way for targeted control.
Published: 2021
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28. DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia

Author: Eilis Hannon, Emma L Dempster, Georgina Mansell, Joe Burrage, Nick Bass, Marc M Bohlken, Aiden Corvin, Charles J Curtis, David Dempster, Marta Di Forti, Timothy G Dinan, Gary Donohoe, Fiona Gaughran, Michael Gill, Amy Gillespie, Cerisse Gunasinghe, Hilleke E Hulshoff, Christina M Hultman, Viktoria Johansson, René S Kahn, Jaakko Kaprio, Gunter Kenis, Kaarina Kowalec, James MacCabe, Colm McDonald, Andrew McQuillin, Derek W Morris, Kieran C Murphy, Colette J Mustard, Igor Nenadic, Michael C O'Donovan, Diego Quattrone, Alexander L Richards, Bart PF Rutten, David St Clair, Sebastian Therman, Timothea Toulopoulou, Jim Van Os, John L Waddington, Wellcome Trust Case Control Consortium (WTCCC), CRESTAR consortium, Patrick Sullivan, Evangelos Vassos, Gerome Breen, David Andrew Collier, Robin M Murray, Leonard S Schalkwyk, and Jonathan Mill
Subjects: epigenetics, DNA methylation, psychosis, schizophrenia, clozapine, Medicine, Science, Biology (General), QH301-705.5
Abstract: We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.
Published: 2021
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29. The role of the chemokine receptor CXCR4 in oral squamous cell carcinoma metastasis

Author: Collier, Jonathan Marc
Subjects: 616.994, Medicine
Abstract: Oral Squamous Cell Carcinoma (OSCC) is the sixth most common cancer worldwide. The greatest cause of mortality and surgical morbidity is due to the common spread of tumour cells from the primary lesion to the lymph nodes of the neck. This pathway is not unique to cancer: under physiological conditions, specific chemokine receptors on the surface of leukocytes mediate cell “homing” to tissues defined by gradients of complimentary chemotactic cytokines (chemokines). The chemokine receptors CXCR4 and CCR7 mediate leukocyte “homing” to secondary lymphoid tissue and have been demonstrated on the surface of a number of carcinomas of the aero-digestive tract. The aim of this project was to determine the role of chemokine receptor expression and function in OSCC metastasis. CXCR4 mRNA expression (microarrays and semi-quantitative RT-PCR) and surface protein production (flow cytometry and immunocytochemistry) was significantly increased in some (but not all) established OSCC cell lines compared with primary oral keratinocytes grown in culture. Examination of clinical samples using a novel, quantitative immunohistochemistry methodology demonstrated a positive association between CXCR4 staining of the cell membrane in primary OSCC lesions and histological evidence of lymph node metastases. CXCR4 over-expression in a constitutively low expressing OSCC cell line (H357) was produced using stable transfection with the CXCR4 insert. Stimulation of CXCR4-bearing OSCC cells with the ligand SDF was shown to mediate statistically significant increases in OSCC cell proliferation in-vitro using a number of complimentary techniques. No effect on apoptosis was demonstrated. The SDF/CXCR4 axis also mediated significant increases in tumour cell chemokinesis, chemotaxis and invasion as measured by a range of in-vitro assays. These results demonstrate a potential role for CXCR4 as part of a panel of prognostic markers for OSCC. Therapeutic strategies aimed at the SDF/CXCR4 axis may be clinically beneficial if the problems of systemic toxicity can be overcome.
Published: 2010

30. Transport of DNA within cohesin involves clamping on top of engaged heads by Scc2 and entrapment within the ring by Scc3

Author: James E Collier, Byung-Gil Lee, Maurici Brunet Roig, Stanislav Yatskevich, Naomi J Petela, Jean Metson, Menelaos Voulgaris, Andres Gonzalez Llamazares, Jan Löwe, and Kim A Nasmyth
Subjects: Cohesin, SMC, DNA entrapment, Medicine, Science, Biology (General), QH301-705.5
Abstract: In addition to extruding DNA loops, cohesin entraps within its SMC-kleisin ring (S-K) individual DNAs during G1 and sister DNAs during S-phase. All three activities require related hook-shaped proteins called Scc2 and Scc3. Using thiol-specific crosslinking we provide rigorous proof of entrapment activity in vitro. Scc2 alone promotes entrapment of DNAs in the E-S and E-K compartments, between ATP-bound engaged heads and the SMC hinge and associated kleisin, respectively. This does not require ATP hydrolysis nor is it accompanied by entrapment within S-K rings, which is a slower process requiring Scc3. Cryo-EM reveals that DNAs transported into E-S/E-K compartments are ‘clamped’ in a sub-compartment created by Scc2’s association with engaged heads whose coiled coils are folded around their elbow. We suggest that clamping may be a recurrent feature of cohesin complexes active in loop extrusion and that this conformation precedes the S-K entrapment required for sister chromatid cohesion.
Published: 2020
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31. Natural variation in autumn expression is the major adaptive determinant distinguishing Arabidopsis FLC haplotypes

Author: Jo Hepworth, Rea L Antoniou-Kourounioti, Kristina Berggren, Catja Selga, Eleri H Tudor, Bryony Yates, Deborah Cox, Barley Rose Collier Harris, Judith A Irwin, Martin Howard, Torbjörn Säll, Svante Holm, and Caroline Dean
Subjects: FLOWERING LOCUS C, field conditions, natural variation, gene expression, Medicine, Science, Biology (General), QH301-705.5
Abstract: In Arabidopsis thaliana, winter is registered during vernalization through the temperature-dependent repression and epigenetic silencing of floral repressor FLOWERING LOCUS C (FLC). Natural Arabidopsis accessions show considerable variation in vernalization. However, which aspect of the FLC repression mechanism is most important for adaptation to different environments is unclear. By analysing FLC dynamics in natural variants and mutants throughout winter in three field sites, we find that autumnal FLC expression, rather than epigenetic silencing, is the major variable conferred by the distinct Arabidopsis FLChaplotypes. This variation influences flowering responses of Arabidopsis accessions resulting in an interplay between promotion and delay of flowering in different climates to balance survival and, through a post-vernalization effect, reproductive output. These data reveal how expression variation through non-coding cis variation at FLC has enabled Arabidopsis accessions to adapt to different climatic conditions and year-on-year fluctuations.
Published: 2020
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32. Characterising the evidence base for advanced clinical practice in the UK: a scoping review protocol

Author: Catrin Evans, Jeanette Eldridge, Roger Knaggs, Paul Hendrick, Peter Harris, Brenda Poku, Ruth Pearce, John McLuskey, Philippa Tomczak, Ruaridh Thow, Joy Conway, and Richard Collier
Subjects: Medicine
Abstract: Introduction A global health workforce crisis, coupled with ageing populations, wars and the rise of non-communicable diseases is prompting all countries to consider the optimal skill mix within their health workforce. The development of advanced clinical practice (ACP) roles for existing non-medical cadres is one potential strategy that is being pursued. In the UK, National Health Service (NHS) workforce transformation programmes are actively promoting the development of ACP roles across a wide range of non-medical professions. These efforts are currently hampered by a high level of variation in ACP role development, deployment, nomenclature, definition, governance and educational preparation across the professions and across different settings. This scoping review aims to support a more consistent approach to workforce development in the UK, by identifying and mapping the current evidence base underpinning multiprofessional advanced level practice in the UK from a workforce, clinical, service and patient perspective.Methods and analysis This scoping review is registered with the Open Science Framework (https://osf.io/tzpe5). The review will follow Joanna Briggs Institute guidance and involves a multidisciplinary and multiprofessional team, including a public representative. A wide range of electronic databases and grey literature sources will be searched from 2005 to the present. The review will include primary data from any relevant research, audit or evaluation studies. All review steps will involve two or more reviewers. Data extraction, charting and summary will be guided by a template derived from an established framework used internationally to evaluate ACP (the Participatory Evidence-Informed Patient-Centred Process-Plus framework).Dissemination The review will produce important new information on existing activity, outcomes, implementation challenges and key areas for future research around ACP in the UK, which, in the context of global workforce transformations, will be of international, as well as local, significance. The findings will be disseminated through professional and NHS bodies, employer organisations, conferences and research papers.
Published: 2020
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33. Economic value of a clinical pharmacist in the Emergency Department

Author: Saskia Van Kemseke, Ellen Oudaert, Hilde Collier, Stephane Steurbaut, Door Lauwaert, Koen Putman, and Ives Hubloue
Subjects: clinical pharmacy, emergency department, medication error, drug related problems, pharmaco-economics, cost avoidance, Medicine
Abstract: Background: Medication errors (MEs) and other drug related problems (DRPs) are common issues on hospital admission. These MEs and DRPs can cause preventable adverse drug events (pADEs) resulting in patient harm with a significant additional cost. The aim of this study was to determine the economic value and the cost-benefit of a clinical pharmacist CP in the ED by applying a theoretical model (University of Sheffield School of Health and Related Research SCHARR). Methods: This retrospective, single-center, observational study was carried out in the ED of a university hospital. Since October 2016, 1 FTE CP is dedicated to the ED. Patient-specific recommendations recorded by the CP during a 1 month period were observed. On admission to the ED, the CP carried out a standardized medication reconciliation and medication review determining pADEs. The most important pADE for each patient was selected and classified for its potential to cause harm using severity rating methods. The net cost avoidance was calculated according to the SCHARR model. We took into account the lower cost limit of the SCHARR model and current inflation. Results: During 1 month (18 weekdays), the CP recorded recommendations for 136 patients (>18 years) admitted to the ED. On ED admission, medication reconciliation was performed for 98 patients with a median of 4 (IQR 2-7) discrepancies/patient. A medication review for both chronic medication and medication prescribed at hospital admission was performed (n=109 and n=98 respectively). Only the CP interventions leading to the most important pADE for each patient were taken into account for the calculation of the cost avoidance. We classified 18 (14.8%) DRPs, 66 (54.1%) DRPs, 37 (30.3%) DRPs and 1 (0.8%) DRP as a pADE with minor or no harm, significant pADE, serious pADE and at least as a severe, life-threatening or fatal pADE, respectively. According to the SCHARR model, this contributed to a net cost avoidance of 40 940. We documented 5 (4.1%) discrepancies without DRP, 53 (43.4%) discrepancies linked to a DRP and 64 (52.5%) DRPs without discrepancy with a cost avoidance of respectively 303, 17 734 and 31 003. The benefit:cost ratio was 5.05:1. Conclusion: A CP, integrated in a multidisciplinary ED team, has an important economic value. Furthermore, the CP enhances medication quality and safety by preventing discrepancies in the chronic medication and by the identification of DRPs on admission at the ED. [SJEMed 2020; 1(1.100): 7S-7S]
Published: 2020
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34. Gut microbiota composition during infancy and subsequent behavioural outcomes

Author: Amy Loughman, Anne-Louise Ponsonby, Martin O'Hely, Christos Symeonides, Fiona Collier, Mimi L.K. Tang, John Carlin, Sarath Ranganathan, Katrina Allen, Angela Pezic, Richard Saffery, Felice Jacka, Leonard C. Harrison, Peter D. Sly, and Peter Vuillermin
Subjects: Medicine, Medicine (General), R5-920
Abstract: Background: Despite intense interest in the relationship between gut microbiota and brain development, longitudinal data from human studies are lacking. This study aimed to investigate the relationship between the composition of gut microbiota during infancy and subsequent behavioural outcomes. Methods: A subcohort of 201 children with behavioural outcome measures was identified within a longitudinal, Australian birth-cohort study. The faecal microbiota were analysed at 1, 6, and 12 months of age. Behavioural outcomes were measured at 2 years of age. Findings: In an unselected birth cohort, we found a clear association between decreased normalised abundance of Prevotella in faecal samples collected at 12 months of age and increased behavioural problems at 2 years, in particular Internalizing Problem scores. This association appeared independent of multiple potentially confounding variables, including maternal mental health. Recent exposure to antibiotics was the best predictor of decreased Prevotella. Interpretation: Our findings demonstrate a strong association between the composition of the gut microbiota in infancy and subsequent behavioural outcomes; and support the importance of responsible use of antibiotics during early life. Funding: This study was funded by the National Health and Medical Research Council of Australia (1082307, 1147980, 1129813), The Murdoch Children's Research Institute, Barwon Health, Deakin University, Perpetual Trustees, and The Shepherd Foundation. The funders had no involvement in the data collection, analysis or interpretation, trial design, recruitment or any other aspect pertinent to the study. Keywords: Infant, Behaviour, Microbiota, Gut-brain axis
Published: 2020
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35. A Patient Perspective: Identifying and Understanding the Barriers Associated with the Diagnostic Delay of Lung Cancer

Author: Lucy Louise Elizabeth Hill, Gareth Collier, and Rachel Elizabeth Gemine
Subjects: Lung cancer, symptom recognition, diagnostic delay, barriers, patient perspective, stigma, knowledge and awareness, smoking status, demographic factors, late stage, Medicine, Diseases of the respiratory system, RC705-779
Abstract: Lung cancer is the most common cancer worldwide and is a fundamental health problem in the UK. Mortality rates are much higher in the UK than other European countries, with overall 5-year survival rates in England and Wales currently as low as 7%. Reducing diagnostic delays may increase the proportion of early stage lung cancer and improve survival, yet the literature surrounding these issues suggests that many people continue to wait a considerable time before presenting symptoms to a clinician. To gain an in-depth understanding into the factors that may influence this delay, this review aims to explore some of the social and psychological barriers that patients face in seeking medical attention for lung cancer symptoms. Likewise, with the majority of lung cancer cases strongly linked to tobacco use, the impact of smoking status and whether it has an effect on an individual’s pathway to diagnosis is imperative to this review. The evidence found suggests that delays in symptom reporting are attributed to low perceptions of risk and a difficulty in recognising lung cancer symptoms early, especially when other comorbidities are present. Additionally, the de-normalisation of smoking appears to have confused understanding regarding risk and reinforced blame and stigma, which ultimately hinders help-seeking behaviours. Future research is thus required to develop strategies and interventions that raise awareness of lung cancer symptoms and empower people to engage in help-seeking behaviours.
Published: 2017

36. Scc2 counteracts a Wapl-independent mechanism that releases cohesin from chromosomes during G1

Author: Madhusudhan Srinivasan, Naomi J Petela, Johanna C Scheinost, James Collier, Menelaos Voulgaris, Maurici B Roig, Frederic Beckouët, Bin Hu, and Kim A Nasmyth
Subjects: Cohesin, CDK1, sister chromatid cohesion, loop extrusion, Wapl, SMC, Medicine, Science, Biology (General), QH301-705.5
Abstract: Cohesin’s association with chromosomes is determined by loading dependent on the Scc2/4 complex and release due to Wapl. We show here that Scc2 also actively maintains cohesin on chromosomes during G1 in S. cerevisiae cells. It does so by blocking a Wapl-independent release reaction that requires opening the cohesin ring at its Smc3/Scc1 interface as well as the D loop of Smc1’s ATPase. The Wapl-independent release mechanism is switched off as cells activate Cdk1 and enter G2/M and cannot be turned back on without cohesin’s dissociation from chromosomes. The latter phenomenon enabled us to show that in the absence of release mechanisms, cohesin rings that have already captured DNA in a Scc2-dependent manner before replication no longer require Scc2 to capture sister DNAs during S phase.
Published: 2019
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37. Systematic techniques for assisting recruitment to trials (START): study protocol for embedded, randomized controlled trials

Author: Paul K. Wallace, Chris Salisbury, Peter Knapp, David Collier, Jo Rick, Anne Kennedy, Adwoa Hughes-Morley, Nicola Small, Sandra Eldridge, Jonathan Graffy, David J. Torgerson, Shaun Treweek, Vichithranie Madurasinghe, and Peter Bower
Subjects: Health Knowledge, Attitudes, Practice, Research Subjects, Psychological intervention, Medicine (miscellaneous), Context (language use), Intervention, Community, Decision support systems, Risk Assessment, law.invention, Decision Support Techniques, Participant information, Access to Information, Study Protocol, Randomized controlled trial, Patient Education as Topic, law, Trial participation, Health care, Medicine, Humans, Pharmacology (medical), Program Development, Randomized Controlled Trials as Topic, Protocol (science), Medical education, business.industry, Communication, Patient Selection, Medical research, Primary care, Research Personnel, 3. Good health, Test (assessment), Systematic review, Multimedia, Sample Size, Practice Guidelines as Topic, Recruitment, business, Protocols
Abstract: Background:Randomized controlled trials play a central role in evidence-based practice, but recruitment of participants, and retention of them once in the trial, is challenging. Moreover, there is a dearth of evidence that research teams can use to inform the development of their recruitment and retention strategies. As with other healthcare initiatives, the fairest test of the effectiveness of a recruitment strategy is a trial comparing alternatives, which for recruitment would mean embedding a recruitment trial within an ongoing host trial. Systematic reviews indicate that such studies are rare. Embedded trials are largely delivered in anad hocway, with interventions almost always developed in isolation and tested in the context of a single host trial, limiting their ability to contribute to a body of evidence with regard to a single recruitment intervention and to researchers working in different contexts. Methods/Design:The Systematic Techniques for Assisting Recruitment to Trials (START) program is funded by the United Kingdom Medical Research Council (MRC) Methodology Research Programme to support the routine adoption of embedded trials to test standardized recruitment interventions across ongoing host trials. To achieve this aim, the program involves three interrelated work packages: (1) methodology - to develop guidelines for the design, analysis and reporting of embedded recruitment studies; (2) interventions - to develop effective and useful recruitment interventions; and (3) implementation - to recruit host trials and test interventions through embedded studies. Discussion:Successful completion of the START program will provide a model for a platform for the wider trials community to use to evaluate recruitment interventions or, potentially, other types of intervention linked to trial conduct. It will also increase the evidence base for two types of recruitment intervention. Trial registration:The START protocol covers the methodology for embedded trials. Each embedded trial is registered separately or as a substudy of the host trial.
Published: 2023

38. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Author: Collier, D. A., Ferreira, I. A. T. M., Kotagiri, P., Datir, R. P., Lim, E. Y., Touizer, E., Meng, B., Abdullahi, A., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Maxwell, P., Shaw, A., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Gleadall, N., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Krishna, B., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Potts, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., D. D. De Bie E. M., Bunclark, K., Josipovic, M., Mackay, M., Michael, A., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. D., Holmes, E., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Smith, K. G. C., Bradley, J. R., Ceron-Gutierrez, L., Cortes-Acevedo, P., Barcenas-Morales, G., Linterman, M. A., Mccoy, L. E., Davis, C., Thomson, E., Mckinney, E., Doffinger, R., Wills, M., Gupta, R. K., Collier, Dami A [0000-0001-5446-4423], Datir, Rawlings P [0000-0003-0521-2144], Smith, Kenneth GC [0000-0003-3829-4326], Linterman, Michelle A [0000-0001-6047-1996], McCoy, Laura E [0000-0001-9503-7946], Thomson, Emma [0000-0003-1482-0889], Lyons, Paul A [0000-0001-7035-8997], Gupta, Ravindra K [0000-0001-9751-1808], and Apollo - University of Cambridge Repository
Subjects: Male, 0301 basic medicine, Aging, Secondary, T-Lymphocytes, Antibodies, Viral, Neutralization, 0302 clinical medicine, 80 and over, Medicine, Viral, Neutralizing, Adult, Aged, Aged, 80 and over, Antibodies, Neutralizing, Autoantibodies, B-Lymphocytes, BNT162 Vaccine, COVID-19 Vaccines, Female, Health Personnel, Humans, Immunization, Secondary, Immunoglobulin A, Immunoglobulin Class Switching, Immunoglobulin G, Immunologic Memory, Inflammation, Interferon-gamma, Interleukin-2, Middle Aged, SARS-CoV-2, Somatic Hypermutation, Immunoglobulin, Spike Glycoprotein, Coronavirus, Vaccination, Vaccines, Synthetic, Immunity, Sars-Cov-2, Vaccines, education.field_of_study, Multidisciplinary, biology, Spike Glycoprotein, 030220 oncology & carcinogenesis, Antibody, Population, Article, Antibodies, 03 medical and health sciences, Immune system, Immunoglobulin, education, business.industry, Synthetic, Somatic Hypermutation, Vaccine efficacy, Coronavirus, 030104 developmental biology, Immunization, Immunology, biology.protein, business
Abstract: Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating., Nature, 596 (7872), ISSN:0028-0836, ISSN:1476-4687
Published: 2021

39. A study of tuberculosis patients' compliance with short course chemotherapy under routine programme conditions in Sierra Leone

Author: Collier, Henrietta Elizabeth
Subjects: 610, Medicine
Published: 1993

40. The surgical management of hidradenitis suppurativa in the United Kingdom: a national survey of care pathways informing the THESEUS study

Author: Kim S Thomas, Rachel Howes, Fiona Collier, Jeremy N. Rodrigues, and John R. Ingram
Subjects: medicine.medical_specialty, Reconstructive surgery, Surgical approach, business.industry, Research, Guideline, medicine.disease, United Kingdom, Treatment efficacy, Hidradenitis Suppurativa, Surgery, Multidisciplinary approach, Intervention (counseling), Family medicine, Critical Pathways, medicine, Humans, Hidradenitis suppurativa, Prospective Studies, business, Prospective cohort study
Abstract: Background The evidence-base underpinning treatment efficacy and effectiveness for hidradenitis suppurativa (HS) is limited, as has been highlighted in the wide-ranging research priorities established by a James Lind Alliance priority-setting partnership (PSP). Understanding the landscape of surgical practice is a key step towards tackling undesired variation in care and resolving treatment uncertainties. This survey of current surgical practice aimed to describe care pathways involving surgeons for the management of HS and surgical approaches to management. Methods In the development of the prospective cohort Treatment of Hidradenitis Suppurativa Evaluation Study (THESEUS), a bespoke electronic surgeon survey was conducted to describe variation in care pathways and surgical preferences in the management of HS. This was disseminated to a pre-defined denominator list of surgeons using local collaborators through the reconstructive surgery trials network (RSTN). Results Key results were small numbers of surgeons working in formal multidisciplinary teams (MDTs) (8/198, 4%), heterogeneity of first-line intervention, low rates of guideline endorsed treatments (laser and deroofing in particular), variation in wound closure methods and follow-up length, and that over half of respondents do not use well-validated outcome instruments to determine treatment success/failure (110/198, 56%). Conclusions This survey demonstrated variation in care, which is likely to be undesirable. Surgeons treating HS patients might consider developing MDTs or referring patients to those with an interest in HS and considering routine outcome measurement. Such steps might reduce variation, increase standardisation of care and improve access to specific treatments.
Published: 2022

41. Validity and severity thresholds for the depression subscale of the affective self rating scale: An equipercentile equating study using classical test theory

Author: Stephen M. Strakowski, DJ Newport, KS Chiang, Mark Bond, Charles B. Nemeroff, SJ Collier, Jrc Almeida, T Lanza di Scalea, J Farrington, SJ Sharp, and DA Spelber
Subjects: Psychiatric Status Rating Scales, education.field_of_study, Psychometrics, genetic structures, Depression, Population, Retrospective cohort study, medicine.disease, behavioral disciplines and activities, Classical test theory, Patient Health Questionnaire, Psychiatry and Mental health, Clinical Psychology, Mood disorders, mental disorders, Item response theory, Equating, medicine, Humans, Self Report, Psychology, education, Depression (differential diagnoses), Retrospective Studies, Clinical psychology
Abstract: The Affective Symptoms Scale (ASRS) is a unique instrument designed to separately measure depressive and manic symptoms in mood disorders. We validated the ASRS against the Patient Health Questionnaire (PHQ-9) and the Quick Inventory of Depressive Symptomatology (QIDS-16).A retrospective study of 258 patients who completed the PHQ-9, QIDS-16 and ASRS as part of routine clinical care. To establish meaningful clinical thresholds for the depression subscale of the ASRS, it was equated with the QIDS and the PHQ-9.The depression subscale of the ASRS had significant positive correlations with the QIDS-16 and the PHQ-9 (respectively, r= 0.8, t[253] = 19.8, p 0.001, and r= 0.8, t[245] = 28.2, p 0.001). The equipercentile equating method with the PHQ-9 indicated that the thresholds corresponded to ASRS depression subscale scores of 5.4, 10.6, 16.1, and 23. Equating with the QIDS indicated that thresholds corresponded to ASRS depression subscale scores of 5.1, 11, 18.4, and 27.5.Limitations include a small sample size that did not allow more detailed statistical analysis, such as Item Response Theory. The population is a heterogenous population at a university outpatient setting.The ASRS depression subscale significantly correlated with the PHQ-9 and QIDS-16. Our proposed threshold scores for the ASRS are 5, 11, 16 and 23 to indicated mild, moderate, severe and very severe depression respectively.
Published: 2022

42. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Author: Obbina Abani, Ali Abbas, Fatima Abbas, Mustafa Abbas, Sadia Abbasi, Hakam Abbass, Alfie Abbott, Nabeel Abdallah, Ashraf Abdelaziz, Mohamed Abdelfattah, Bushra Abdelqader, David Abdo, Basir Abdul, Althaf Abdul Rasheed, Ajibode Abdulakeem, Rezan Abdul-Kadir, Amina Abdulle, Abdulfatahi Abdulmumeen, Rasheed Abdul-Raheem, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer Ul Amna Abeer Ul Amna, Katrina Abernethy, Adebanke Aboaba, Hani Abo-Leyah, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Hyacinth-John Abu, Ahmed Abu-Arafeh, Syed M Abubacker, Akata Abung, Yaa Aceampong, Amaka Achara, Devikumar Acharya, Sarah Acheampong, Janet Acheson, Andres Acosta, Catherine Acton, Jacqueline Adabie-Ankrah, Sara Adair, Fiona Adam, Matthew Adam, Huzaifa Adamali, Carol Adams, Charlotte Adams, Kate Adams, Lisa Adams, Richard Adams, Tim Adams, Kirsty Adcock, Jemaimah Addai, Ade Adebiyi, Ken Adegoke, Vicki Adell, Debo Ademokun, Sherna Adenwalla, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Joyce Adeyemi, Rina Adhikary, Gabrielle Adkins, Adnan Adnan, John Aeron-Thomas, Debbie Affleck, Dominic Affron, Carmel Afnan, Muhammad Afridi, Zainab A Aftab, Meenakshi Agarwal, Rachel Agbeko, Chris Agbo, Penny Agent, Sunil Aggarwal, Arameh Aghababaie, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Humayun Ahmad, Mohammad Ahmad, Syed Ahmad, Asim Ahmed, Bilal Ahmed, Forizuddin Ahmed, Hamze Ahmed, Iram Ahmed, Irshad Ahmed, Khaled Ahmed, Liban Ahmed, Mahin Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Sara Ahmed, Sophia Ahmed, Syed Ahmed, Syed Haris Ahmed, Roa Ahmed Ali, Sana Ahmed, Sana Ahmer, Dhiraj Ail, Mark Ainsworth, Giulia Airoldi, Myriam Aissa, Lindianne Aitken, Bini Ajay, Francis Ajeneye, Abdulakeem Ajibode, Ayesha Ajmi, Tahir Akbar, Naim Akhtar, Nasim Akhtar, Nauman Akhtar, Suha Akili, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Olajide Akinwumiju, Olugbenro Aktinade, Ahmad Al Aaraj, Asma Al Balushi, Majd Al Dakhola, Aladdin Al Swaifi, Eslam Al-Abadi, Narendra Aladangady, Ayaz Alam, Sajid Alam, Abbas Al-Asadi, Karina Al-Asadi, Kyriaki Alatzoglou, Manaf Al-Bayati, Paul Albert, Lorraine Albon, Gemma Alcorn, Stephen Alcorn, Aggie Aldana, David Alderdice, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ana Alegria, Alison Alexander, John Alexander, Peter D G Alexander, Charlotte Alford, Julyan Al-Fori, Laith Alghazawi, Bahij Al-Hakim, Shams Al-Hity, Ali Ali, Asad Ali, Fawzia R Ali, Hoodo Ali, Jawad Ali, Mariam Ali, Mohammad Ali, Nayab Ali, Oudai Ali, Sabira Ali, Sakina Ali, Syed Ali, Abid Alina, Fine Aliyuda, Katrin Alizadeh, Maithem Al-Jibury, Saba Al-Juboori, Majid Al-Khalil, Moutaz Alkhusheh, Allameddine Allameddine, Fiona Allan, Rachel Allan, Alison Allanson, Robert Allcock, Beverley Allen, Eireann Allen, Jess Allen, Kerry Allen, Laura Allen, Louise Allen, Poppy Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Kathryn Allison, Bethan Allman, Lynne Allsop, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Inji Alshaer, Rustam Al-Shahi Salman, Warkaq Al-Shamkhani, Bashar Al-Sheklly, Sara Altaf, Mary Alvarez, Balaal Alyas, Maysaa Alzetani, Susan Amamou, Noor Amar, Sakkarai Ambalavanan, Sarah-Jayne Ambler, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Kenneth Amenyah, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Syed Amin, Tara Amin, Amjad Amjad, Neelma Amjad, Mariam Ammoun, Victoria Amosun, Khaled Amsha, Pugh Amy, Atul Anand, Rekha Anand, Samantha Anandappa, Julie Anderson, Kevin Anderson, Laura Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rory Anderson, Wendy Anderson, Prematie Andreou, Angela Andrews, Antonette Andrews, Jill Andrews, Susan Andrews, Gregory Andrikopoulos, Kanayochukwu Aneke, Andrew Ang, Wan Wei Ang, Tammy Angel, Aramburo Angela, Paola Angelini, Lazarus Anguvaa, Oleg Anichtchik, Millicent Anim-Somuah, Krishnan Aniruddhan, Jessica Annett, Patrick J Anstey, Rebekah Anstey, Alpha Anthony, Aaron Anthony-Pillai, Philip Antill, Zhelyazkova Antonina, Varghese Anu, Muhammad Anwar, George Apostolides, Aristeidis Apostolopoulos, Sarah Appleby, Diane Appleyard, Maia Far Aquino, Bianca Araba, Samuel Aransiola, Mariana Araujo, Emily Arbon, Ann Archer, Denise Archer, Simon Archer, Christian Ardley, Ana-Maria Arias, Ryoki Arimoto, Charlotte Arkley, Charlotte Armah, Ilianna Armata, Adam Armitage, Ceri Armstrong, Maureen Armstrong, Sonia Armstrong, Sylvia Armstrong-Fisher, Philippa Armtrong, Heike Arndt, Clare Arnison-Newgass, David Arnold, Rachael Arnold, Sarah Arnott, Dhawal Arora, Kavan Arora, Pardeep Arora, Rishi Arora, Andrea Arroyo, Arslam Arter, Ayush Arya, Rita Arya, Denisa Asandei, Adeeba Asghar, Catherine Ashbrook-Raby, Glen Ashby, Helen Ashby, Jan Ashcroft, John Ashcroft, Samuel Ashcroft, Deborah Asher, Ayesha Ashfaq, Ben Ashford, Suhail Ashgar, Abdul Ashish, Sally Ashman-Flavell, Sundar Ashok, Abd-El-Aziz Ashour, Muhammad Z Ashraf, Saima Ashraf, Mohammad B Ashraq, Deborah Ashton, Susan Ashton, Andrew Ashworth, Rebecca Ashworth, Arshia Aslam, Harshini Asogan, Abigail Asquith, Atif Asrar, Omar Assaf, Raine Astin-Chamberlain, Richard Athay-Hunt, Deborah Athorne, Billie Atkins, Christopher Atkins, Stacey Atkins, John Atkinson, Vicki Atkinson, Brygitta Atraskiewicz, Claire Atterbury, Abdul Ahmad Attia, Rita Atugonza, Paula Aubrey, Avinash Aujayeb, Aye Chan Thar Aung, Hnin Aung, Kyaw Thu Aung, Ni Aung, Yin Aung, Zaw Myo Aung, Emily Austin, Karen Austin, Abdusshakur Auwal, Miriam Avery, Joanne Avis, Georgina Aviss, Cristina Avram, Paula Avram, Gabriel Awadzi, Atia Awan, Aszad Aya, Eman Ayaz, Amanda Ayers, Jawwad Azam, Mohammed Azharuddin, Ghazala Aziz, N Aziz, Ali Azkoul, Ashaari Azman Shah, Giada Azzopardi, Hocine Azzoug, Fiyinfoluwa Babatunde, Melvin Babi, Babiker Babiker, Gayna Babington, Matthew Babirecki, Marta Babores, Adetona O Babs-Osibodu, Sammy Bacciarelli, Roudi Bachar, Gina Bacon, Jenny Bacon, Bibi Badal, Gurpreet R Badhan, Shreya Badhrinarayanan, Joseph P Bae, Sibel Bafekr Mishamandani, Alice Baggaley, Amy Baggott, Graham Bagley, Dinesh Bagmane, Lynsey Bagshaw, Kasra Bahadori, James Bailey, Katie Bailey, Lindsey Bailey, Liz Bailey, Morgan Bailey, Pippa Bailey, Sarah Bailey, Stephen Bailey, Hamish Baillie, J Kenneth Baillie, Jennifer Bain, Sanchia Baines, Vikram Bains, Aimi Baird, David Baird, Susan Baird, Tracy Baird, Yolanda Baird, Aiysha Bajandouh, Charles Baker, Emma Baker, Evelyn Baker, Johanne Baker, Josephine Baker, Kenneth Baker, Rebecca Baker, Terri-Anne Baker, Victoria Baker, Hugh Bakere, Nawar Bakerly, Michelle Baker-Moffatt, Nauman Bakhtiar, Panos Bakoulas, Julie Balaam, Niranjan Balachandran, Andrea Balan, Theodosios Balaskas, Madhu Balasubramaniam, Alison Balcombe, Alexander Baldwin, Ashley Baldwin, Caron Baldwin, Danielle Baldwin, 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Cameron, Sheena Cameron, Christian Camm, Renee F D Cammack, Alison Campbell, Amy Campbell, Barbara Campbell, Bridget Campbell, Debbie Campbell, Helen Campbell, Hilary Campbell, Jonathan Campbell, Mark Campbell, Robyn Campbell, Wynny Campbell, Quentin Campbell Hewson, Julie Camsooksai, Ana Canabarro, Lisa Canclini, Shaula Mae Candido, Janie Candlish, Cielito Caneja, Johnathon Cann, Ruby Cannan, Emma Cannon, Michael Cannon, Petra Cannon, Vivienne Cannons, Jane Cantliff, Ben Caplin, Santino Capocci, Noemi Caponi, Angelika Capp, Anne Capps-Jenner, Thomas Capstick, Ishmael Carboo, Nuria Cardenas, Mary Cardwell, Rachel Carey, Simon Carley, Tammy Carlin, Andrew Carlton, Samantha Carmichael, Mandy Carnahan, Rebecca Carnegie, Charlotte Caroline, Emily Carpenter, Jodi Carpenter, David Carr, Sharon Carr, Anna Carrasco, Samantha Carrington, Zoe Carrington, Paul Carroll, Caroline Carron, Anne Carstairs, Jonathan Carter, Michael Carter, Moira Carter, Paul Carter, Penny Carter, Steven Carter, Simon 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Eric Chiang, Angela Chiapparino, Rosavic Chicano, Zviedzo A Chikwanha, Sam Chilcott, Phillipa Chimbo, KokWai Chin, Wen Jie Chin, Rumbidzai Chineka, Amol Chingale, Karen Chinn, Vashira Chiroma, Heather Chisem, Claire Chisenga, Ben Chisnall, Carolyn Chiswick, Sunder Chita, Nihil Chitalia, Matthew Chiu, Brenda Chivima, Catherine Chmiel, Soha Choi, Willy Choon Kon Yune, Vandana Choudhary, Sarah Choudhury, Bing-Lun Chow, Fateha Chowdhury, Mahibbur Chowdhury, Shahid Chowdhury, Victoria Christenssen, Peter Christian, Alexander Christides, Fiona Christie, Daniel Christmas, Thereza Christopherson, Mark Christy, Paris Chrysostomou, Yunli Chua, Shabs Chucha, Dip Chudgar, Richard Chudleigh, Srikanth Chukkambotla, Michael E Chukwu, Izu Chukwulobelu, Chi Y Chung, Ben Church, Elaine Church, Sara R Church, David Churchill, Nicole Cianci, Nick Ciccone, Paola Cicconi, Paola Cinardo, Zdenka Cipinova, Bessie Cipriano, Sarah Clamp, Melanie Clapham, Edel Clare, Sarbjit Clare, Andrew Clark, Charlotte Clark, 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Dearden, Alison Deary, Catherine Deas, Samuel Debbie, Gabor Debreceni, Vashist Deelchand, Matthew Deeley, Joanne Deery, Emmanuel Defever, Raji Dehulia, Max Deighton, Manuela Del Forno, Arnold Dela Rosa, Lisa Delaney, Amanda Dell, Carrie Demetriou, David DeMets, Jane Democratis, Jacqueline Denham, Emmanuelle Denis, Laura Denley, Craig Denmade, Kathy Dent, Martin Dent, Elise Denton, Tom Denwood, Nishigandh Deole, Darshita Depala, Maria Depante, Randle Derbyshire, Susan Dermody, Amisha Desai, Asmita Desai, Purav Desai, Sanjeev Deshpande, Vai Deshpande, Brendan Devine, Sirjana Devkota, Nicola Dewland, Prakash Dey, Vishal Dey, Rogin Deylami, Jazz Dhaliwal, Kevin Dhaliwal, Jas Dhalliwal, Mandeep Dhanda, Sundip Dhani, Amandeep Dhanoa, Mili Dhar, Devesh Dhasmana, Aman Dhesi, Ekanjali Dhillon, Reiss Dhillon, Pamela Diamond, Priya Dias, Stephanie Diaz, Kayleigh Diaz-Pratt, Debbie Dickerson, Pamela Dicks, Stuart Dickson, Julie Dijo, Sean Dillane, Sarah Diment, Paul Dimitri, Maria Dineen, ThaiHa Dinh, Tri Dinh, Alex Dipper, Laura Dirmantaite, Lisa Ditchfield, Sarah Diver, Lavanya Diwakar, Caroline Dixon, Giles Dixon, Stephen Dixon-Mould, Brice Djeugam, Petr Dlouhy, Laurence Dobbie, Marinela Dobranszky Oroian, Charlotte Dobson, Lee Dobson, Marie Docherty, David Dockrell, James Dodd, Jackie Dodds, Rebecca Dodds, Steve Dodds, Richi Dogra, Erin Doherty, Warren Doherty, Yumiko Doi, Iain Doig, Eleanor Doke, Daniel Dolan, Mark Dolman, Rozzie Dolman, Lisa Donald, Callum Donaldson, Christopher Donaldson, Denise Donaldson, Gillian Donaldson, Kate Donaldson, Joanne Donnachie, Christopher Donnelly, Eilish Donnelly, Ronan Donnelly, Aravindhan Donohoe, Gemma Donohoe, Bryan Donohue, Sinead Donton, Emma Dooks, Grainne Doran, Kane Dorey, Sharon Dorgan, Amanda Dornan, Moonira Dosani, Davinder Dosanjh, Paula Dospinescu, Katie Douglas, Jonathan Douse, Lucy Dowden, Michelle Dower, Kerry Dowling, Sud Dowling, Nicola Downer, Charlotte Downes, Rob Downes, Thomas Downes, Damian Downey, Philippa 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Eagles, Joanne Early, Melissa Earwaker, Nicholas Easom, Clare East, Kim East, Amy Easthope, Fraser Easton, Caroline Eaton, Caroline Eaton-Howell, Ruth Eatough, Adrian Ebbs, Oluwadamilola Ebigbola, Daniel Ebner, Martin Ebon, Sinan Eccles, Chloe Eddings, Michael Eddleston, Maureen Edgar, Katharine Edgerley, Nicholas Edmond, Julie Edmonds, Dave Edmondson, Mary Edmondson, Tracy Edmunds, Alexandra Edwards, Catherine Edwards, Joy Edwards, Kennedy Edwards, Mandy Edwards, Tomos Edwards, Jenny Eedle, Dawn Egginton, Loveth Ehiorobo, Sarah Eisen, Ugochukwu Ekeowa, Mohamed Ekoi, Ayomide Ekunola, Soha El Behery, Moulod El-Agnaf, Mohamed Elbeshy, Kate El-Bouzidi, Jennifer Elder, Mohammed El-Din, Diana Eleanor, Ibrahim Eletu, Eman Elfar, Mayy Magdy Elgamal, Amr Elgohary, Stellios Elia, Jennifer Elias, Tania Elias, Nadia Elkaram, Mohammed El-Karim, Andrew Victor Elkins, Julie Ellam, Nikki Ellard, Laura Nicola Ellerton, Lucy Elliot, Amy Elliott, Chris Elliott, Fiona Elliott, Kerry Elliott, Scott Elliott, Toby Elliott, Annie Ellis, Ann-Marie Ellis, Christine Ellis, Kay Ellis, Kaytie Ellis, Tak-Yan Ellis, Yvette Ellis, Megan Ellison, Rahma Elmahdi, Einas Elmahi, Hannah-May Elmasry, Mohammed Elmi, Najla Elndari, Omer Elneima, Mohamed Elokl, Ahmed Elradi, Mohamed Elsaadany, Sally El-Sayeh, Hana El-Sbahi, Tarek Elsefi, Karim El-Shakankery, Robert Elshaw, Hosni El-Taweel, Sarah Elyoussfi, Jonathan Emberey, Jonathan R Emberson, John Emberton, Julian Emmanuel, Ingrid Emmerson, Michael Emms, Florence Emond, Marieke Emonts, Nicu Enachi, Angila Engden, Katy English, Emma Entwistle, Hene Enyi, Marios Erotocritou, Helen Escreet, Peter Eskander, Hanif Esmail, Lise Estcourt, Amy Evans, Brynach Evans, Chris Evans, Daren Evans, Debra Evans, Gail Evans, Gareth Evans, Jennifer Evans, Lisa Evans, Lynn Evans, Margaret Evans, Michelle Evans, Mim Evans, Morgan Evans, Ranoromanana Evans, Ryan Evans, Teriann Evans, Terry John Evans, Tony Eve, Caroline Everden, Serenydd Everden, Hayley Evison, Lynsey Evison, Penny Eyton-Jones, Jacqueline Faccenda, Leila Fahel, Youstina Fahmay, Sara Fairbairn, Terry Fairbairn, Andy Fairclough, Louise Fairlie, Mark Fairweather, Anne Fajardo, Naomi Falcone, Euan Falconer, Jonathan Falconer, John Fallon, Andrea Fallow, David Faluyi, Victoria Fancois, Qayyum Farah, Novin Fard, Amr Farg, Margaret Farinto, Adam Farmer, Katie Farmer, Toni Farmery, Samantha Farnworth, Faiyaz Farook, Hadia Farooq, Sidrah Farooq, Fiona Farquhar, Karen Farrar, Aaron Farrell, Barbara Farrell, James Farthing, Syeda Farzana, Rahmatu Fasina, Azam Fatemi, Mina Fatemi, Nibah Fatimah, Maria Faulkner, Saul N Faust, Joe Fawke, Sinmidele Fawohunre, Abul Fazal, Kelly Feane, Simon Fearby, Alex Feben, Federico Fedel, Daria Fedorova, James Feely-Henderson, Christopher Fegan, Mae Felongco, Lynsey Felton, Tim Felton, Kate Fenlon, Andrea Fenn, Isabelle Fenner, Ciara Fenton, Melisa Fenton, Cameron Ferguson, Jenny Ferguson, Kathryn Ferguson, Katie Ferguson, Stephanie Ferguson, Susan Ferguson, Susie Ferguson, Victoria Ferguson, Denzil Fernandes, Candida Fernandez, Eduardo Fernandez, Maria Fernandez, Sonia Fernandez Lopez, Callum Jeevan Fernando, Ahmed Feroz, Pietro Ferranti, Thais Ferrari Gersogamo, Eleanor Ferrelly, Alexandra Ferrera, Emma Ferriman, Nicholas Fethers, Ben Field, Janet Field, Rebecca Field, Karen Fielder, Lindsey Fieldhouse, Andra Fielding, Julie Fielding, Len Fielding, Sarah Fielding, Asma Fikree, Sarah Ann Filson, Sarah Finbow, Debbie Finch, Joanne Finch, Laurie Finch, Joanne Finden, Natalie Fineman, Lauren Finlayson, Adam Finn, Joanne Finn, Clare Finney, Sofia Fiouni, Jo Fiquet, Dani Fisher, Emily Fisher, James Fisher, Neil Fisher, Meadow Fisher Crisp, Daniel Fishman, Krystofer Fishwick, Lorraine Fitzgerald, Chloe Fitzpatrick-Creamer, Jan Flaherty, Michael Flanagan, Charles Flanders, Cathy Flatters, Julie Fleming, Lucy Fleming, Paul Fleming, William Flesher, Alison Fletcher, Jonathan Fletcher, Lucy Fletcher, Simon Fletcher, Sophie Fletcher, Karen Flewitt, Christopher Flood, Ian Floodgate, Vincent Florence, Sharon Floyd, Kelly Flynn, Rachel Flynn, Sara Flynn, Claire Foden, Adama Fofana, Georgina Fogarty, Claire Foley, Paul Foley, Linda Folkes, Daniela Mock Font, Evodian Fonyonga, Aiwyne Foo, Jane Foo, Andrew Foot, Jayne Foot, Jane Forbes, Jamie Ford, Kathy Ford, Jennifer Foreman, Caroline Fornolles, Adam Forrest, Ellie Forsey, Miranda Forsey, Thomas Forshall, Elliot Forster, Julian Forton, Emily Foster, Joseph Foster, Rachel A Foster, Tracy Foster, Theodora Foukanelli, Angela Foulds, Ian Foulds, Folakemi Fowe, Emily Fowler, Robert Fowler, Stephen Fowler, Caroline Fox, Claire Fox, Daniel Fox, Heather Fox, Jonathan Fox, Lauren Fox, Natalie Fox, Olivia Fox, Simon Fox, Sarah-Jane Foxton, Yasin Fozdar, Rebecca Frake, Alex Francioni, Olesya Francis, Rebecca Francis, Sarah Francis, Theodora Francis-Bacon, Jason Frankcam, Helen Frankland, Gayle Franklin, Jessica Franklin, Darron Franks, Catherine Fraser, Laura Fraser, Sharon Frayling, Martyn Fredlund, Matthew Free, Carol Freeman, Elaine Freeman, Hannah Freeman, Nicola Freeman, Clare Freer, Ian Freestone, Eleanor French, Matthew Frise, Renate Fromson, Claire Froneman, Adam Frosh, John Frost, Victoria Frost, Oliver Froud, Rachel Frowd, Arun Fryatt, Jake Fryer, Janet Fu, Bridget Fuller, Liz Fuller, Neil Fuller, Tracy Fuller, Duncan Fullerton, Jenny Fullthorpe, Carrie Fung, Gayle Fung, Sarah Funnell, John Furness, Charlene Furtado, Andrew Fyfe, Nytianandan G, Elizabeth Gabbitas, Claire Gabriel, Diana Gabriel, Hadiza Gachi, Rose Gad, Joshua Gahir, Sarveen Gajebasia, Katarzyna Gajewska-Knapik, Zacharoula Galani, Christopher Gale, Hugo Gale, Rebecca Gale, Swetha Gali, Karen Galilee, Bernadette Gallagher, Jude Gallagher, Rosie Gallagher, William Gallagher, Joanne Galliford, Catherine Galloway, Chris Galloway, Emma Galloway, Jacqui Galloway, James Galloway, Laura Gamble, Liz Gamble, Brian Gammon, Jaikumar Ganapathi, Ramesh Ganapathy, Kaminiben Gandhi, Sarah Gandhi, Usha Ganesh, Abrar Gani, Emma-James Garden, Antoni D Gardener, Emma Gardiner, Jill Gardiner, Michael Gardiner, Phil Gardiner, Siobhan Gardiner, Caroline Gardiner-Hill, Jonathan Gardner, Mark Garfield, Atul Garg, Nathan Garlick, Justin Garner, Lucie Garner, Zoe Garner, Kimberley Garnett, Robert Garney, Rosaline Garr, Michael Garstka, Peter Gartan, Florence Garty, Rachel Gascoyne, Hyeriju Gashau, Noha Gasmalseed, Michaela Gaspar, Aoife Gatenby, Erin Gaughan, Alok Gaurav, Mariana Gavrila, Jane Gaylard, Emma Gaywood, Catherine Geddie, Alison Geddis, Ian Gedge, Sarah Gee, Minerva Gellamucho, Karzan Gelly, Leila Gelmon, Sandra Gelves-Zapata, Gemma Genato, Susan Gent, Natalie Geoghegan, Chloe George, Sam George, Tina George, Simon Georges, Domonique Georgiou, Peter Gerard, Leigh Gerdes, Louise Germain, Helen Gerrish, Abel Getachew, Louise Gethin, Hisham Ghanayem, Amardeep Ghattaoraya, Anca Gherman, Alison Ghosh, Justin Ghosh, Sudhamay Ghosh, Sarra Giannopoulou, Malick Gibani, Andrew Gibb, Ben Gibbison, Kerry Gibbons, Alex Gibson, Bethan Gibson, Kimberley Gibson, Kirsty Gibson, Sian Gibson, Cat Gilbert, Jeanette Gilbert, Joanne Gilbert, Kayleigh Gilbert, Sean Gilchrist, Benjamin Giles, Mandy Gill, Rose Gill, Lynne Gill, Paul Gillen, Annelies Gillesen, Katherine Gillespie, Matt Gillespie, Elizabeth Gillham, Andrew Gillian, Deborah Gilliland, Robert Gillott, Danielle Gilmour, Kate Gilmour, Theodora Giokanini-Royal, Anna Gipson, Joanna Girling, Rhian Gisby, Angelena Gkioni, Aikaterini Gkoritsa, Effrossyni Gkrania-Klotsas, Amy Gladwell, James Glanville, Jessica Glasgow, Susannah Glasgow, Jon Glass, Lynn Glass, Sharon Glaysher, Lisa Gledhill, Ana Glennon, John Glover, Kyle Glover, Jan Glover Bengtsson, Chevanthy Gnanalingam, Julie Goddard, Wendy Goddard, Emily Godden, Jo Godden, Gillian Godding, Emma Godson, Gerry Gogarty, Sukanya Gogoi, Aiky Goh, Rebeca Goiriz, Sriya Gokaraju, Philip Gold, Raphael Goldacre, Arthur Goldsmith, Portia Goldsmith, Darren Gomersall, Lucia Gomez, Raquel Gomez-Marcos, Ali Gondal, Celia Gonzalez, Jack Goodall, Bob Goodenough, Laura Goodfellow, James Goodlife, Camelia Goodwin, Elizabeth Goodwin, Jayne Goodwin, Paula Goodyear, Rajiv Gooentilleke, Sharif Goolam-Hossen, Michelle Goonasekara, Sheila Gooseman, Shameer Gopal, Peter Gordon, Sally Gordon, Hugh Gorick, Caitlin Gorman, Claire Gorman, Stuart Gormely, Diana Gorog, Jan Gorry, Michelle Gorst, Thomas Gorsuch, Jayshreebahen Gosai, Rebecca Gosling, Sally Gosling, Georgina Gosney, Vanessa Goss, Dzintars Gotham, Naomi Gott, Elizabeth Goudie, Amanda Gould, Angela Gould, Susan Gould, Lysander Gourbault, Anna Gouveia, Abha Govind, Sharon Gowans, Girish Gowda, Rohit Gowda, Pauline Gowdy, Hannah Gower, Thomas Gower, Pankaj Goyal, Sunil Goyal, Sushant Goyal, Beverley Graham, Clive Graham, Jane Graham, Jonathan Graham, Justin Graham, Libby Graham, Sharon Graham, Matthew Graham-Brown, Julia Grahamslaw, Gianluca Grana, Tracyanne Grandison, Louis Grandjean, Alison Grant, Ann Grant, David Grant, 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Griffiths, Yvonne Griffiths, Sofia Grigoriadou, Steph Grigsby, Paul Grist, Stephen Grist, Evelina Grobovaite, Clarissa Grondin, Rachel Groome, Liliana Grosu, Jenny Grounds, Margaret Grout, Helen Grover, Jayne Groves, Neil Grubb, Julie Grundy, Francesca Guarino, Sharada Gudur, Sharazeq Guettari, Shivang Gulati, Vikas Gulia, Pumali Gunasekera, Malin Gunawardena, Kirun Gunganah, Jessica Gunn, Emma Gunter, Alok Gupta, Atul Gupta, Rajeev Gupta, Richa Gupta, Rishi Gupta, Tarun Gupta, Vineet Gupta, Ankur Gupta-Wright, Victoria Guratsky, Alvyda Gureviciute, Sambasivarao Gurram, Bhawana Gurung, Shraddha Gurung, Hazel Guth, Ruth Habibi, Berkin Hack, Pamela Hackney, Christian Hacon, Aiman Haddad, Denise Hadfield, Michalis Hadjiandreou, Nikolaos Hadjisavvas, Leah Hadzik, Anna Haestier, Nauman Hafiz, Rana Hafiz-Ur-Rehman, Javed Hafsa, Samantha Hagan, Jack W Hague, Rosemary Hague, Kate Haigh, Christina Haines, Scott Hainey, Morton Hair, Brigid Hairsine, Juraj Hajnik, Anne Haldeos, Writaja Halder, Jennie Hale, Carmel Halevy, Paul Halford, William Halford, Alistair Hall, Anthony Hall, Claire Hall, Elizabeth Hall, Emma Hall, Fiona Hall, Helen Hall, Jennifer Hall, Kathryn Hall, Bill Hall, Jan Hallas, Kyle Hallas, Charles Hallett, Becky-Lee Halls, Heather Halls, Maryam Hamdollah-Zadeh, Bilal Hameed, Imran Hamid, Mohamad Hamie, Bethany Hamilton, Fergus Hamilton, Leigh Hamilton, Nicola Hamilton, Ruth Hamlin, Eleanor Hamlyn, Beatrice Hammans, Shirley Hammersley, Kate Hammerton, Bev Hammond, Leah Hammond, Sara Hammond, Fiona Hammonds, Ibrahim Hamoodi, Karen Hampshire, Elizabeth Hampson, Jude Hampson, Lucy Hampson, Ozan Hanci, Ian Hancock, Sadiyah Hand, Jasmine Handford, Soran Handrean, Sarah Haney, Sheharyar Hanif, E Hanison, Alison Hanlon, Jennifer Hannah, Amy Hannington, Merhej Hannun, Aidan Hanrath, Anita Hanson, Jane Hanson, Kathryn Hanson, Steve Hanson, Helen Hanwell, Mazhar Ul Haq, Ala Haqiqi, Monjurul Haque, Lesley Harden, Zoe Harding, Simon Hardman, Joanna Hardy, Kumar Haresh, Rachel Harford, Beverley Hargadon, Carolyn Hargreaves, Emily Hargreaves, James Hargreaves, Alice Harin, Mohammed Haris, Edward Harlock, Sandra Harlow, Paula Harman, Tracy Harman, Mark Harmer, Muhammad A Haroon, Charlie Harper, Fiona Harper, Heather Harper, Melanie Harper, Peter Harper, Rosemary Harper, Sarah Harrhy, Sian Harrington, Yasmin Harrington-Davies, Jade Harris, Jess Harris, John Harris, Laura Harris, Marie-Clare Harris, Naomi Harris, Nichola Harris, Sophie Harris, Alex Harrison, David Harrison, Julie Harrison, Laura Harrison, Melanie Harrison, Rowan Harrison, Susie Harrison, Thomas Harrison, Wendy Harrison, Elizabeth Harrod, Ciaran Hart, Dominic Hart, Lisa Hartley, Rosemary Hartley, Ruth Hartley, Tom Hartley, William Hartrey, Phillipa Hartridge, Stuart Hartshorn, Heli Harvala, Alice Harvey, Angela Harvey, Max Harvey, Catherine Harwood, Helen Harwood, Brigitte Haselden, Kazi Hashem, Mohammed Hashimm, Tadaaki Hashimoto, Imranullah Hashmi, Sarah Haskins, Zena Haslam, Adil Hassan, Ali Hassan, Wagae UI Hassan, Waqar Ul Hassan, Sapna Hassasing, Jane Hassell, Philip Hassell, Alex Hastings, Bethany Hastings, Janice Hastings, Stephanie Hatch, Jonathan Hatton, Sheryl Haviland, May Havinden-Williams, Stefan Havlik, Daniel B Hawcutt, Kadean Hawes, Liz Hawes, Nicola Hawes, Annie Hawkins, Catherine Hawkins, Nancy Hawkins, Tanya Hawkins, Dan Hawley, Ed Hawley-Jones, Edward Haworth, Cathy Hay, Amna Hayat, Jamal Hayat, Mohamed-Riyal Hayathu, Tamsin Haydon, Anne Hayes, Jonas Hayes, Kate Hayes, Melony Hayes, Vanessa Hayes, Fiona Hayes, Patrick Hayle, Chloe Haylett, Antara Hayman, Melanie Hayman, Matthew Haynes, Richard Haynes, Rachel Hayre, Sarah Haysom, James Hayward, Patrick Haywood, Tracy Hazelton, Phoebe Hazenberg, Zhengmai He, Elizabeth Headon, Carrie Heal, Brendan Healy, Amy Hearn, Angela Heath, Rowan Heath, Diane Heaton, Kerry Hebbron, Gemma Hector, Andy Hedges, Katrine Hedges, Cheryl Heeley, Elaine Heeney, Rajdeep Heire, Ulla Hemmila, Cassie Hemmings, Scott 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Susie Holt, Alexandra Holyome, Marie Home, Toni Home, Renate Homewood, Kate Hong, Laura Hontoria del Hoyo, Clare Hooper, Sarah Hoosdally, Samantha Hope, Susan Hope, Bridget Hopkins, Peter W Horby, Stephanie Horler, Anil Hormis, Daniel Hornan, Nicola Hornby, Zoey Horne, Latoya Horsford, Megan Horsford, Mark Horsford, Valana Horsham, Alexander Horsley, Ashley Horsley, Elizabeth Horsley, Sarah Horton, Nicola Horton-Turner, Jane Hosea, Toby Hoskins, Muhammad S Hossain, Rashed Hossain, Leanne Hostler, Maxine Hough, Sarah Hough, Brittany Houghton, Catherine Houghton, Iain Houghton, Kathryn Houghton, Rebecca Houlihan, Angela Houston, Hamish Houston, Tawedzegwa Hove, Roseanna Hovvels, Lee How, Laura Howaniec, Laura Howard, Linda Howard, Lucy Howard, Sarah Howard, Stuart Howard, Richard Howard-Griffin, Alison Howarth, Diane Howarth, Serena Howe, Mark Howells, Lyn Howie, Kerry Howlett, Sophie Howlett, Joanne Hoyle, Josh Hrycaiczuk, Naing Zaya Htoon, Su Htwe, Ying Hu, Chiang Ooi Huah Huah, Abby Huckle, Shahzya Huda, Alison Hudak, Lisa Hudig, Alex Hudson, Cara Hudson, Heather Hudson, Peter Hudson, Oli Hudson, Alison Hufton, Connor Huggins, Alistair Hughes, Eithne Hughes, Emma Hughes, Gareth Hughes, Heather Hughes, Luke Hughes, Rachel Hughes, Rebecca Hughes, Samantha Hughes, Stephen Hughes, Vikki Hughes, Wesley Hughes, Lukas Huhn, Ching Hui, Ruth Hulbert, Diana Hull, Grace Hull, Robert Hull, Amanda Hulme, Peter Hulme, Wendy Hulse, George Hulston, Ryan Hum, Laura Humber, Megan Hume, Charlotte Humphrey, Ismay Humphreys, Alasdair Humphries, Joanne Humphries, Lena Hunold, Fiona Hunt, Kristen Hunt, Luke Hunt, Sophie Hunt, Al Hunter, Alexandra Hunter, Isobel Hunter, Karl Hunter, Neil Hunter, George Huntington, Elizabeth Hurditch, Cian Hurley, Katrina Hurley, Mohammed A Husain, Syeda Yusra Husaini, Coralie Huson, Afreen Hussain, Ibraar Hussain, Ifza Hussain, Mohammad Hussain, Muhammad Hussain, Reda Hussain, Sajid Hussain, Samia Hussain, Sanniah Hussain, Wasim Hussain, Yasmin Hussain, Mohammed Hussam El-Din, Raheem Hussein, Rebecca Hussey, Camille Hutchinson, Dorothy Hutchinson, Elizabeth Hutchinson, John Hutchinson, Claire Hutsby, Paula Hutton, Daniella Hydes, Jamie Hyde-Wyatt, Niamh Hynes, Megan Hyslop, Mazen Ibraheim, Abdalla Ibrahim, Ahmed Ibrahim, Asil Ibrahim, Mohamed Ibrahim, Monzeer Ibrahim, Wadah Ibrahim, Adetokunbo I Idowu, Muhammad Idrees, Hina Iftikhar, Mawara Iftikhar, Chukwuemeka Igwe, Mohammad Ijaz, Amaju Ikomi, Clare Iles, Stamatina Iliodromiti, Mary Ilsley, Lorna Ilves, La'ali Imam-Gutierrez, Christopher Imray, Alison Imtiaz, Haider Imtiaz, Claire Ingall, Jack Ingham, Julie Ingham, Rory Ingham, Tejas Ingle, Jennifer Inglis, Anne Ingram, Luke Ingram, Peter Inns, Ken Inweregbu, Andreea A Ionescu, Ana Ionita, Ilian P Iordanov, Anil Ipe, Adil Iqbal, Madiha Iqbal, Mohammed Iqbal, Faisal Iqbal Sait, Jane Ireland, Robert Irons, Mohannad Irshad, Muhammad S Irshad, Janice Irvine, Val Irvine, Pamela Irving, Robert Irving, Mina Ishak, Erica Isherwood, Aminul Islam, Abdurrahman Islim, Ali Ismail, Omar Ismail, Caroline Ison, M'hamedi Israa, Sharon Isralls, Ali Issa, Monica Ivan, Catrina Ivel, Chineze Ivenso, Ashleigh Ivy, Sophie Iwanikiw, Karen Ixer, Menaka Iyer, Mia Iyer, Calum Jack, Amanda Jackson, Anthony Jackson, Ben Jackson, Beth Jackson, Douglas Jackson, Ella Jackson, Hayley Jackson, Helen Jackson, Jane Jackson, Julie Jackson, Karin Jackson, Lauren Jackson, Melanie Jackson, Nicola Jackson, Shane Jackson, Sharon Jackson, Nikita Jacob, Patricia Jacob, Reni Jacob, Nicola Jacques, Terri-Lisa Jacques-Brown, Anisa Jafar, Daniel Jafferji, Ali Jaffery, Chandrashekar Jagadish, Vijay Jagannathan, Sam Jaggard, Mandeep Jagpal, Fernandez R Jaime, Neemisha Jain, Seema Jain, Susan Jain, Sanjay Jaiswal, Danyal Jajbhay, Thomas Jaki, Bintou Jallow, Yusuf Jaly, Sabine Jamal, Zeba Jamal, Yasmin Jameel, Albie James, Christie James, Kate James, Lee James, Linda James, Mark James, Nicholas James, Olivia James, Rebecca James, Ruth James, Tracy James, Jack Jameson, Aaron Jamison, Phoebe Jane, Azara Janmohamed, Sabrina Jansz, Deepa Japp, Lorraine Jappy, Victor Jardim, Catherine Jardine, Emma Jarnell, Ellie Jarvie, Ann Jarvis, Claire Jarvis, Lisa Jarvis, Rosina Jarvis, Patrycja Jastrzebska, Hafsa Javed, Mays Jawad, Lona Jawaheer, Kauky Jawaid, Anu Jayachandran, Dinakaran Jayachandran, Angelina Jayakumar, Deepak Jayaram, Ravi Jayaram, Geeshath Jayasekera, Thilina Jayatilleke, Abi Jayebalan, Saman Jeddi, Vandana Jeebun, Mohammad S Jeelani, Zeynab Jeewa, Emma Jefferson, Katie Jeffery, Helen Jeffrey, Jenni Jeffrey, Rachel Jeffrey, Sue Jeffrey, Nathan Jeffreys, Benjamin Jeffs, Debbie Jegede, Taylor Jemima, Ifan Jenkin, Alison Jenkins, Christopher Jenkins, David Jenkins, Elinor Jenkins, Sarah Jenkins, Sian Jenkins, Stephen Jenkins, Jacqui Jennings, Louise Jennings, Rebecca Jennings, Virginia Jennings, Ellen Jerome, Douglas Jerry, Ellen Jessup-Dunton, Jorge Antonio Jesus Silva, Champa Jetha, Kishan Jethwa, Jeby Jeyachandran, Visuvanathan Jeyakumar, Dharshana Jeyapalan, Shaman Jhanji, Khoo Jian, Zhixin Jiao, Laura Jimenez, Ana Jimenez Gil, Jithin Jith, Teishel Joefield, Navraj Johal, Karine Johannessen, Aisyah Johari, Annie John, Anu John, Navin John, Sarah John, Emma Johns, Margaret Johns, Anne-Marie Johnson, Antoinette Johnson, David Johnson, Emma Johnson, Gillian Johnson, Kathryn Johnson, Katie Johnson, Luke Johnson, Mark Johnson, Nelsonseelan Johnson, Oliver Johnson, Rachel Johnson, Tracy Johnson, Zoe Johnson, Claire Johnston, Janet Johnston, Laura Johnston, Susan Johnston, Victoria Johnston, Dawn Johnstone, Ed Johnstone, Janet Johnstone, Manohar Joishy, Adam Jones, Alistair Jones, Annabel Jones, Ben Jones, Bryony Jones, Carys Jones, Ceri Jones, Charlotte Jones, Christine E Jones, Debra Jones, Emily Jones, Gareth Jones, Geraldine Jones, Hazel Jones, Jac Jones, James Jones, Jamie Jones, Jessica Jones, Jonathon Jones, Julie Jones, Karen Jones, Kate E Jones, Kevin Jones, Laura Jones, Laura M Jones, Lorna Jones, Louise Jones, Mathew Jones, Nicola Jones, Paul Jones, Rhianna Jones, Ruth E Jones, Samantha Jones, Sophie Jones, Stefanie Jones, Steve Jones, Taya Jones, Tim Jones, Tracey Jones, Ramya Jonnalagadda, Rebecca Jordache, Annette Jose, Sanal Jose, Anna Joseph, Joseph Joseph, Rosane Joseph, Sibet Joseph, Dhaara Joshi, Mehul Joshi, Pratichi Joshi, Revati Joshi, Benz Josiah, Tiffany Joyce, Adriel Ju Wen Kwek, Edward Jude, Parminder Judge, Jessica Juhl, Sirisha Jujjavarapu, Mark Juniper, Edmund Juszczak, Deepthi Jyothish, Kasamu Kabiru Dawa, Mark Kacar, Katarina Kacinova, Nikhil Kadam, Rebecca Kahari, Gail Kakoullis, Azad Kala Bhushan, Richard JK Kalayi, Roobala Kaliannan Periyasami, Efthymia Kallistrou, Seika Kalsoom, Elisa Kam, John Kamara, Mohamed Kamara, Ajay Kamath, Prakash Kamath, Ravindra Kamath, Siddharth Arun Kamerkar, Nick Kametas, Musaiwale Kamfose, Arul Kandaswamy, Leia Kane, Osei Kankam, Thogulava Kannan, Abhinav Kant, Vikas Kapil, Ritoo Kapoor, Sonal Kapoor, Sourjya Kar, Janaka Kara, Vasita Kara, Marina Karakantza, Rona Kark, Nicholas Karunaratne, Natashja Kasianczuk, Vidya Kasipandian, Rizwan Kassam, Janarth Kathirgamachelvam, Victoria Katsande, Kulbinder Kaul, Daljit Kaur, Dervinder Kaur, Jasmin Kaur, Jaspreet Kaur, Satvinder Kaur, Zunaira Kausar, Mohammad AA Kawser, Andrea Kay, Sarah Kay, Jossy N Kayappurathu, Callum Kaye, Ahemd Kazeem, Naved Kazi, Sharon Kaznica, Samantha Kearley, Rachel Kearns, Nichola Kearsley, Joanne Keating, John Keating, Liza Keating, Elizabeth Keddie-Gray, Katie Keen, Natalie Keenan, Jonathan Kefas, Stephen Kegg, Laura Keith, Uzoamaka Keke, Tosin Kelani, Joanne Kellett, Jeremy Kellington, Alison Kelly, Conor Kelly, David Kelly, Diane Kelly, Dominic Kelly, Emma Kelly, Laura Kelly, Martin Kelly, Michael Kelly, Rosalind Kelly, Sinead Kelly, Stephen Kelly, Thomas Kelly, Mary Kelly-Baxter, Marketa Keltos, Timothy Kemp, Kelly Kemsley, Alexandra Kendall-Smith, Sarah Kennard, Ann Kennedy, Caroline Kennedy, James Kennedy, Sophie Kennedy-Hay, Julia Kenny, Kelly Kent, Melanie Kent, Lynne Keogan, Alexander Keough, Clement Kerlin, A Kerr, Andrew Kerr, Maria Kerr, Caroline Kerrison, Anthony Kerry, Samantha Kershaw, Helen Kerslake, Ian Kerslake, Helen Kerss, Jocelyn Keshet-Price, Margaret Kevern, Georgina Keyte, Abdul Khadar, Ali Khalid, Muhammad U Khalid, Syed Khalid, Amir Khalil, Asma Khalil, Sijjad Khalil, Abubakar Khan, Ali Khan, Al-Imran Khan, Arham Khan, Asad Khan, Aurangzeb Khan, Burhan Khan, Camran Khan, Fatimah Khan, Kausik Khan, Malik Aamaz Khan, Marria Khan, Mehrunnisha Khan, Mohammad Khan, Mohammed Khan, Nayeem Khan, Omar Khan, Rahe Khan, Rahila Khan, Sabiya Khan, Shabana Khan, Shahul Khan, Shoaib Khan, Tasaduksultan Khan, Waseem Khan, Usman F Khatana, Jibran Khatri, Jyoti Khatri, Hafiza Khatun, Taslima Khatun, Mena Kheia, Jacyntha Khera, Htet Ei Khin, Najaf Khoja, Kiran Khokhar, Jayne Khorsandi, Chloe Khurana, Faith Kibutu, Andrew Kidd, Michelle Kidd, Joe Kidney, Shane Kidney, Will Kieffer, James Kilbane, Caroline Kilby, Eileen Killen, Susan Kilroy, Bomee Kim, Jee Whang Kim, Sarah Kimber, Andy King, Barbara King, Jennifer King, Kirsten King, Rachel King, Sarah King, Tony King, Victoria King, Emily King-Oakley, Laura Kingsmore, Andy King-Venables, Fiona Kinney, Sidra Kiran, Jeremy Kirk, Jodie Kirk, Daniel Kirkbride, Amy Kirkby, Ian Kirker, Emily Kirkham, Gemma Kirkman, Ursula Kirwan, Kelly Kislingbury, Toby Kitching, Laura Kitto, Lauren Kittridge, Sarah Klaczek, Frieder Kleemann, Susan Kmachia, Chris Knapp, Lucy Knibbs, Alicia Knight, Fraser Knight, Marian Knight, Sarah Knight, Steven Knight, Tom Knight, Ellen Knights, Jane Knights, Toby Knights, Martin Knolle, Carol Knott, Charlotte Knowles, Karen Knowles, Laurence Knowles, Emily Knox, Lucy Knox, Oliver Koch, Ronan Kodituwakku, Gouri Koduri, Aisha Koirata, Eirene Kolakaluri, Magdalena Kolodziej, Eirini Kolokouri, Keith Kolsteren, Samantha Kon, Niladri Konar, Mari Kononen, Athanasios Konstantinidis, Hui Fen Koo, Imogen Koopmans, Emmanuela Kopyj, Laura Korcierz, James Korolewicz, George Koshy, Chris Kosmidis, Jalpa Kotecha, Easwari Kothandaraman, Leonidas Koukouflis, Koushan Kouranloo, Rukhsana Kousar'c, Margarita Kousteni, Maja Kovac, Alex Kozak Eskenazia, Kestutis Krasauskas, Raghu Krishnamurthy, Vinodh Krishnamurthy, Manju Krishnan, Hari Krishnan, Suzanne Krizak, Sean Krupej, Agnieszka Kubisz-Pudelko, Soren Kudsk-Iversen, Aurimas Kudzinskas, Chirag Kukadiya, Nainesha Kulkarni, Aditi Kumar, Mayur Kumar, Ramesh Kumar, Ravi Kumar, Rita Kumar, Rupa Kumar, Satish Kumar, Vimal Kumar, Arun Kundu, Heinke Kunst, Amit Kurani, Mohammed Kurdy, Rincy Kurian, Vimal Kurmars, Cameron Kuronen-Stewart, Ranganai S Kusangaya, Vlad Kushakovsky, Mandy Kuunal, Apexa Kuverji, Amma Kyei-Mensah, Thyra Kyere-Diabour, Moe Kyi, Nyan M Kyi, Laura Kyle, Karali-Tsilimpari Kyriaki, Julius Labao, Louise Lacey, Nikki Lack, Emma Ladlow, Heather Lafferty, Shondipon Laha, Sushil Lahane, Clement Lai, James Lai, Emma Laing, Robert Laing, Inez Laing-Faiers, Emily Laity, Michelle Lake, Nicki Lakeman, David Lalloo, Fiona Lalloo, Alison Lam, Fiona Lamb, Lucy Lamb, Thomas Lamb, Nick Lambe, Pauline Lambert, Claudia Lameirinhas, Mohammed KG Lami, Abigail Lamikanra, Holly Lamont, Michal Lamparski, Djillali Lamrani, Christine Lanaghan, Rebecca Lanaway, Ivone Lancona-Malcolm, Julia Lancut, Geraldine Landers, Martin J Landray, Matthew Lane, Nicholas Lane, Alidih Lang, Stephen Lang, Daniel Langer, Margaret Langley, Charles Langoya, Emily Langthorne, Taiya Large, Wojciech Lason, Anna Last, Scott Latham, John Latham-Mollart, Afzal Latheef, Darren Latimer, Nang Latt, Carly-Jane Lattimore, Dawn Lau, Eva Lau, Myra Laurenson, Hou Law, Jennifer Law, Jessica Law, Penny Law, Richard Law, Colin Lawler, Mark Lawley, Emma Lawrence, Jo Lawrence, Neil Lawrence, Ryan Lawrie, Jemima Lawson, Joanne Lawson, Louise Lawson, Rebecca Lawton, Michael Lay, Christine Laycock, Reina Layug, Maria Lazo, Vietland Le, Amelia Lea, William Lea, Ian Leadbitter, Thomas Leahy, Richard Lean, Lorna 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Kateryna Macconaill, Chloe Macdonald, Stuart MacDonald, Tania MacDonald, Claire Macfadyen, James G Macfarlane, Jill Macfarlane, Laura Macfarlane, Cara MacGuigan, Lisa MacInnes, Iain MacIntyre, Jill MacIntyre, Kirsten Mack, Callum Mackay, Euan Mackay, Laura Mackay, Alexander Mackenzie, Matt Mackenzie, Robert MacKenzie Ross, Ami Mackey, Patricia Mackey, Fiona Mackie, Robert Mackie, Carolyn Mackinlay, Claire Mackintosh, Katherine Mackintosh, Sheila MacLennan, Mary Joan MacLeod, Michael Macmahon, Andrew MacNair, Catherine Macphee, Iain Macpherson, Catriona Macrae, Allan MacRaild, Eilidh MacVean, Alannah Madden, Mary Madden, Norman Madeja, Karen Madgwick, Pradeep Madhivathanan, Madhavi Madhusudhana, Harriet Madiyiko, Alpha Madu, Lorraine Madziva, Marion Mafham, Nick Magee, Frederick Magezi, Tim Maggs, Negar Maghsoodi, Christopher Magier, Marios Magriplis, Kathryn Maguire, Natasha Mahabir, Subramanian Mahadevan-Bava, Anjanie Maharajh, Ajit Mahaveer, Bal Mahay, Kanta Mahay, Hibo Mahdi, 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Margarit, Georgios Margaritopoulos, Mike Margarson, Fernandez M Maria del Rocio, Teresa Maria Pfyl, Victor Mariano, Helen Maria-Osborn, Ashleigh Maric, Grace Markham, John Markham, Maria Marks, Pamela Marks, Elisabeth Marouzet, Arran Marriott, Cheryl Marriott, Nemonie Marriott, Brian Marsden, Karen Marsden, Paul Marsden, Sarah Marsden, Tracy Marsden, Robyn Marsh, Adam Marshall, Andrew Marshall, Gail Marshall, Henry Marshall, Jaimie Marshall, James Marshall, Jenna Marshall, Nicola Marshall, Riley Marshall, Jennifer Marshall, Samantha Marston, Emmeline Martin, Hayley Martin, Hope Martin, Jane Martin, Karen Martin, Kate Martin, Laila Martin, Michael Martin, Noelia Martin, Tim Martin, Winston Martin, Sarah Martin, Tim Martindale, Marcus Martineau, Alexander Martinez, Lauren Martinez, Jose Carlos Martinez Garrido, Juan Martin-Lazaro, Olivia Martins, Lucas Martins Ferreira, Vijay Kumar Maruthamuthu, Gemma Maryan, Roman Mary-Genetu, Sam Maryosh, Vidan Masani, Diego Maseda, Sheila Mashate, Yasaman Mashhoudi, Al Mashta, Izhaq Masih, Sanna Masih, Nick Maskell, Perry Maskell, Matthew Masoli, Lynn Mason, Rebecca Mason, Richard Mason, Ruth Mason, Claire Mason, Mohammad Masood, Mohammad T Masood, Syed Masood, Syed SME Masood, Aaqib Masud, Lear Matapure, Cristina Matei, Ropafadzo Matewe, Manraj Matharu, Stephy Mathen, Alex Mather, Nicole Mather, Jonathan Mathers, Joanna Matheson, Amal Mathew, Anna Mathew, Moncy Mathew, Verghese Mathew, Caroline Mathews, Jesha Mathews, Kate Mathias, Marion Mathie, Darwin Matila, Wadzanai Matimba-Mupaya, Nashaba Matin, Elina Matisa, Max Matonhodze, Elijah Matovu, Jaysankar Mattappillil, Alison J Matthews, Heather Matthews, Helen Matthews, Sue Matthews, Gwynn Matthias, Fiona Maxton, Adam Maxwell, Gemma Maxwell, Veronica Maxwell, James May, Joanne May, Oliver May, Philippa May, Irving Mayanagao, Matthew Maycock, Graham Mayers, Lee Maynard, Shelley Mayor, Ibreaheim Mazen, Andrea Mazzella, Nyambura Mburu, Mercy Mbwembwe, Martyn McAdam, Eleanor 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Nagarajan, Imrun Nagra, Deepak Nagra, Mina Naguib, Kirushthiga Naguleswaran, K Shonit Nagumantry, Kevin Naicker, Sarveshni Naidoo, Gireesha Naik, Rishi Naik, Samir Naik, Devu S Nair, Rajiv Nair, Tanushree Nair, Jay Naisbitt, Kerry Naismith, Sri Nallapareddy, Soum Nallapeta, Arumugan Nallasivan, Uttam Nanda, Aarti Nandani, Ali Raza Naqvi, Asadullah Naqvi, Sara Naqvi, Shruthi Narayan, Sophia Nasa, Dominic Nash, Nader Nasheed, Abdul Nasimudeen, Umer Nasir, Marwan Nassari, Tahir Nasser, Anushka Natajaran, Anuja Natarajan, Geetha Natarajan, Nalin Natarajan, Nikhila Natarajan, Rajkumar Natarajan, Noel Nathaniel, Mala Nathvani, Priyan Nathwani, George Nava, Neena Navaneetham, Jeya Navaratnam, Helen Navarra, Sadaf Naveed, John Navin, Khuteja Nawaz, Sarfaraz Nawaz, Shasta Nawaz, Bonilla Nayar, Suzanne Naylor, Moez Nayyar, Farrah Naz, Mobeena Naz, Salima Nazarali, Babak Nazari, S Nazir, Sehar Nazir, Dumisani Ncomanzi, Onyine Ndefo, Alan Neal, Elaine Neary, Mostafa Negmeldin, Paula Neill, Hector 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Liz Park, Angela Parker, Ben Parker, Carmel Parker, Emma Parker, Fiona Parker, Jacob Parker, Julie Parker, Laura Parker, Lucy Parker, Sara Parker, Sean Parker, Tina Parker, Kirstin Parkin, Anna Parkinson, Jill Parkinson, Lisa Parkinson, Valerie Parkinson, Chetan Parmar, Mamta Parmar, Viraj Parmar, Victoria Parris, Helen C Parry, Siobhan Parslow-Williams, Maria Parsonage, Abigail Parsons, Penny Parsons, Sarah Parsons, Richard Partridge, Kevin Parvin, Kirsten Pass, Lauren Passby, Juan Pastrana, Mital Patal, Sarah Patch, Aamie Patel, Alkesh Patel, Amisha Patel, Dakshesh Patel, Darshna Patel, Hemani Patel, Jaymik Patel, Kamal Patel, Kayur Patel, Kiran Patel, Krish Patel, Manish Patel, Martyn Patel, Mehul Patel, Naleem Patel, Nehalbhai Patel, Prital Patel, Priti Patel, Rebecca Patel, Saagar Patel, Soonie Patel, Trishna Patel, Vishal Patel, Sangeeta Pathak, Nazima Pathan, Alexandra Patience, Donna Patience, Abigail Patrick, Georgie Patrick, Jean Patrick, Simon Patten, Ben Pattenden, Ann Patterson, Charlotte Patterson, Linda Patterson, Molly Patterson, Pauline Patterson, Robert Patterson, Daniel Paul, Janice Paul, Roshni Paul, Leigh Pauls, Stephane Paulus, Amelia Pavely, Susan Pavord, Brendan Payne, David Payne, Elizabeth Payne, Ruth Payne, Tammy Payne, Abby Peacock, Linda Peacock, Louise Peacock, Sarah Peacock, Henry Peake, Rupert Pearse, Andrew Pearson, Daniel Pearson, Harriet Pearson, Karen Pearson, Kirsty Pearson, Samuel A Pearson, Sandra Pearson, Alice Peasley, Hilary Peddie, Russell Peek, Claire Pegg, Suzannah Peglar, Benjamin H Peirce, Claire Pelham, Belinda Pelle, Abigail Pemberton, Melchizedek Penacerrada, Anthony Pender, Carmel Pendlebury, Jessica Pendlebury, Sarah Pendlebury, Rachel Penfold, William Penlington, Catherine Penman, Julie Penman, Rachel Penman, Justin Penner, Kristi Penney, Alistair Penny, James Penny, Justin Pepperell, Huw Peregrine, Adriana Pereira, Ana Pereira, Rita Pereira, Carlota Pereira Dias Alves, Parmi Perera, Elena Perez, Jane Perez, Tanaraj Perinpanathan, Lakshmi Periyasamy, Francesca Perkins, Rachel Perkins, Elizabeth Perritt, Alison Perry, Emily Perry, Meghan Perry, Terrie Perry, Thomas M Perumpral, Guilherme Pessoa-Amorim, Ruth Petch, Lionel Peter, Cecilia Peters, Craig Peters, Jayne Peters, Mark Peters, Steve Peters, Tim Peters, Remy Petersen, Alexandra Peterson, Leon Peto, Iulia Petras, Ilianna Petrou, Boyanka Petrova, Mirela Petrova, Paul Pfeffer, Mysore Phanish, Paul Phelan, Christopher Philbey, Jennifer Philbin, Neil Philips, Alex Phillips, Danielle Phillips, Dylan Phillips, Karen Phillips, Pat Phillips, Rachael Phillips, Katherine Philpott, Marie Phipps, Virach Phongsathorn, Mandeep Phull, Masroor M Phulpoto, Myat TT PI, Sara Pick, James Pickard, Charlotte Pickering, Gillian Pickering, Thomas Pickett, Hayleah Pickford, Joanna Pickles, Benjamin Pickwell-Smith, Natalia Pieniazek, Charlie Piercy, Angelo Pieris, Samia Pilgrim, Paul Anthony Pillai, Zoe Pilsworth, Heather Pinches, Stacey Pinches, Julia Pinder, Kirsty Pine, Muni Tejha Pinjala, Stefania Pintus, Graeme Piper, James Piper, Richard Pipes, Tasneem Pirani, Marcus Pittman, Sally Pitts, Nicolene Plaatjies, Aiden J Plant, Naomi Platt, Robert Pleass, Rutger Ploeg, Laura Plummer, Charles Plumptre, Jonathan Pobjoy, Tatiana Pogreban, Stephen Poku, David Poles, Rachel Pollard, Louisa Pollock, Oluwamayowa Poluyi, Gary John Polwarth, Fiona Pomery, Ponmurugan Ponnusamy, Suresh Ponnusamy, Aravind Ponnuswamy, Inês Ponte Bettencourt dos Reis, Suman Pooboni, Alice Poole, Christopher Poole, Lorraine Poole, Lynda Poole, Michele Poole, Sharon Poon, Tajinder Poonian, Ella Poppitt, Christopher Porada, David Porter, Jo Porter, Linda Porter, Ross Porter, Kelly Postlethwaite, Narayana Pothina, Priyadarshan Potla, Dorota Potoczna, Jason Pott, Alison Potter, Jean Potter, Kenzi Potter, Sarah Potter, Tracey Potter, Elspeth Potton, Joanne B Potts, Julie Potts, Kathryn Potts, Una Poultney, Katherine Poulton, Vanessa Poustie, Geneen Powell, James Powell, Jordan Powell, Deborah Power, Nick Power, Gillian Powter, Joseph Poxon, Robin Poyner, Vidushi Pradhan, Helena Prady, Aalekh Prasad, Krishna Prasad, Maanvi Prasad, Fredy Prasanth Raj, Sangeetha Prasath, Sindhuja Pratheepkumar, Anezka Pratley, Steven Pratt, David Preiss, Claire Prendergast, Lynn Prentice, Peter Prentice, Verity Prescott, Laura Presland, Catharine Prest, Stephen Preston, Martha Pretorius, Natalie Prevatt, Sandra Prew, Ashley Price, Carly Price, Claire Price, David Price, Elizabeth Price, Nathan Price, Vivien Price, Nicole Priddee, Anne Priest, Kate Priestley, Jimena Prieto, Lorraine Primrose, Clare Prince, Judith Prince, Laura Prince, Janet Pring, Shirley Pringle, Veronika Pristopan, Kelly Pritchard, Lucy Pritchard, Rhys Pritchard, Simon Pritchard, Verma Priyash, Andrew Procter, Clare Proctor, Rebecca Proudfoot, Ben Prudon, David Pryor, Solomon Pudi, Joanne Pugh, Lawrence Pugh, Mark T Pugh, Nichola Pugh, Richard Pugh, Veronika Puisa, Kirandip Punia, Saleel Punnilath Abdulsamad, Laura Purandare, Claire Purcell, Corrina Purdue, Bally Purewal, Molly Pursell, Gregory Purssord, Sarah Purvis, Kathryn Puxty, Zoe Puyrigaud, Michael Pynn, Tariq Qadeer, Mohammad Qayum, Corrine Quah, Sheena Quaid, Nathaniel Quail, Charlotte Quamina, Donna Quashie, Alice Quayle, Eleanor Quek, Siobhan Quenby, Xinyi Qui, Vanessa Quick, Julie Quigley, Juan-Carlos Quijano-Campos, Andrew Quinn, Tom Quinn, Amy Quirk, Quratulain Quratulain, Danya Qureshi, Ehsaan Qureshi, Hafiz Qureshi, Hasanain Qureshi, Khadija Qureshi, Nawaz Qureshi, Qurratulain Qurratulain, Saad Qutab, Muhammad S Rabbani, Syed Rabbani, Wayne Rabin, Simon Rabinowicz, Madalina Raceala, Raissa Rachman, Laura Rad, Jane Radford, Liz Radford, Jayachandran Radhakrishnan, Cecillia Rafique, Jethin Rafique, Muhammad Rafique, Ravi Ragatha, Aiswarya Raghunathan, Abigail Raguro, Shankho D Raha, Sana Rahama, Karen Rahilly, Faisal Rahim, Abdul H Rahimi, Haseena R Rahimi, Muhammad Rahman, Salim Ur Rahman, Sharon Rainey, Lenka Raisova, Arjun Raj, Pradeep Rajagopalan, Nithy Rajaiah, Arvind Rajasekaran, Aylur Rajasri, Thurkka Rajeswaran, Jyothi Rajeswary, Jeyanthy Rajkanna, Gayathri Rajmohan, Ruth Rallan, David Ralphs, Katherine Ralston, Maximilian Ralston, Matsa Ram, Balaji Ramabhadran, Fathima Ramali, Mohamed Ramali, Athimalaipet Ramanan, Shashikira Ramanna, Maheshi Ramasamy, Dhanishta Ramdin, Jozel Ramirez, Mylah Ramirez, Geshwin Ramnarain, Lidia Ramos, Shanthi Ramraj, Alex Ramshaw, Aleem Rana, Ghulam F Rana, Rehman Rana, Abby Rand, James Rand, Helen Randall, Harpal Randheva, Poonam Ranga, Manmeet Rangar, Harini Rangarajan, Sameer Ranjan, Poormina Ranka, Rajesh Rankhelawon, Haley Ranton, Anita Rao, Sandhya Rao, Sanjay Rao, Deepak Rao, Anuja Rasarathnam, Alia Rashid, Khalid Rashid, Simbisai Ratcliff, Sam Ratcliffe, Sophy Ratcliffe, Sanjeev Rath, Mohmad I Rather, Selina Rathore, Aravinden Ratnakumar, Jonathan Ratoff, Deepa Rattehalli, Jason Raw, Hywel Rawlins, Gautam Ray, Michelle Ray, Adam Raymond-White, Dana Raynard, Benjamin Rayner, Nicola Rayner, Amy Raynsford, Salman Razvi, Zarine Razvi, Kerry Read, Sarah Read, Ajay Reddy, Anvesh Reddy, Harsha Reddy, Radhika Reddy, Ravi Reddy, Aine Redfern-Walsh, Alex Redome, Joan Redome, Michelle Reece, Anna Reed, John Reed, Andrew Rees, Grace Rees, Ian Rees, James Rees, Martyn Rees, Sarah Rees, Stephanie Rees, Tabitha Rees, Fiona Regan, Karen Regan, Susan Regan, Kanchan Rege, Ahmed Rehan, A Rehman, Shoib Rehman, Zainab Rehman, Ada Reid, Andrew Reid, Jennifer Reid, Jeremy Reid, Sharon Reid, Mkyla Reilly, Robert Reilly, Shonagh Reilly, Christina Reith, Alda Remegoso, Dinakaran Rengan, Stephen Renshaw, Remya Renu Vattekkat, Henrik Reschreiter, Mark Revels, Glynis Rewitzky, Charles Reynard, Dominic Reynish, Peter Reynolds, Piero Reynolds, Jonathan Rhodes, Naghma Riaz, Emily Rice, Matthew Rice, Emily Rich, Mel Rich, Alison Richards, Debbie Richards, Emma Richards, Liz Richards, Patricia Richards, Suzanne Richards, Carol Richardson, Celia Richardson, Eric 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Louise Rowe-Leete, Benjamin Rowlands, Megan Rowley, Aparajita Roy, Subarna Roy, Anna Roynon-Reed, Sam Rozewicz, Alison Rudd, Anna Rudenko, Senthan Rudrakumar, Banu Rudran, Shannon Ruff, Prita Rughani, Sharon Rundell, Jeremy Rushmer, Rosemary Rushworth, Darren Rusk, Peter Russell, Richard Russell, Cristina Russo, Marieke Rutgers, Aidan Ryan, Brendan Ryan, Lucy Ryan, Matthew Ryan, Pat Ryan, Phil Ryan, Declan Ryan-Wakeling, Nick Rylance, M Saad, Javeson Sabale, Suganya Sabaretnam, Umar Sabat, Noman Sadiq, Emma Sadler, Maria-Isabel Saez-Garcia-Holloway, Ashiq Saffy, Beth Sage, Harkiran Sagoo, Sobia Sagrir, Rajnish Saha, Sian Saha, Nikhil Sahdev, Sarvjit Sahedra, Jagdeep Sahota, Nooria Said, Sreekanth Sakthi, Hikari Sakuri, Murthy Saladi, Abdul Salam, Sofiyat Salawu, Armorel Salberg, Erika Salciute, Gina Saleeb, Mumtaz Saleh, Hizni Salih, Laylan Salih, Sarah Salisbury, SiteEneye Saliu, Rustam Salman, Angela Salmon, Jenny Salmon, Nichola Salmons, Dario Salutous, Mfon Sam, Sally Sam, Tinashe 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Rachel Saunders, Samantha Saunders, Anne Saunderson, Heather Savill, Karishma Savlani, Gauri Saxena, Matthew Saxton, Amrinder Sayan, Diane Scaletta, Marta Scally, Deborah Scanlon, Jeremy Scanlon, Lyndsay Scarratt, Sean Scattergood, Alvin Schadenberg, Wendy Schneblen, Rebecca Schofield, Samuel Schofield, David Scholes, Karen Scholes, Alex Schoolmeesters, Natasha Schumacher, Nicola Schunke, Martin Schuster Bruce, Karin Schwarz, Antonia Scobie, Tim Scorrer, A. 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Anand Shah, Bhavni Shah, Momin Shah, Neil Shah, Pallav Shah, Priyank Shah, Qasim Shah, Sarfaraz H Shah, Snehal Shah, Suraj Shah, Syed Shah, Wajid Shah, Saarma Shahad, Sousan Shahi, Sipan Shahnazari, Muhammad Shahzeb, Aisha Shaibu, Zara Shaida, Amina Y Shaikh, Maliha Shaikh, Rajit Shail, Mariya Shaji, Muhammad Shakeel, Korah Shalan, Nadia Shamim, Kazi Shams, Alison Shanahan, Thomas Shanahan, Shaminie Shanmugaranjan, Hamed Sharaf, Muhammad Sharafat, Asir Sharif, Ajay Sharma, Akhilesh Sharma, Ash Sharma, Bhawna Sharma, Mona Sharma, Ojasvi Sharma, Poonam Sharma, Rajeev Sharma, Sanjeev Sharma, Sarkhara Sharma, Shriv Sharma, Sonal Sharma, Alexander Sharp, Charles Sharp, Gemma Sharp, Paula Sharratt, Phoebe Sharratt, Katherine Sharrocks, Emma Sharrod, Christopher Shaw, Daisy Shaw, David Shaw, Deborah Shaw, Joanne Shaw, Jonathan Shaw, Lisa Shaw, Tomos G Shaw, Anna Shawcross, Jill Shawe, Lou Shayler, Khuram Shazad, Sophy Shedwell, Jonathan Sheffield, Zak Shehata, Arshiya Sheik, Asif Sheikh, Noorann Sheikh, Laura Sheldon, Benjamin Shelley, Sarah Shelton, Anil Shenoy, Julie Shenton, Amy Shepherd, Kate Shepherd, Lorna Shepherd, Scott Shepherd, Rhian Sheppeard, Helen Sheridan, Ray Sheridan, Samuel Sherridan, Leanne Sherris, Susanna Sherwin, Shaad Shibly, Roger Shiers, Chiaki Shioi, Anand Shirgaonkar, Kim Shirley, Adebusola Shonubi, Angela Short, Richard Shortland, Rob Shortman, Rohan Shotton, Sarah Shotton, Ervin Shpuza, Nora Shrestha, Karen Shuker, Jack Shurmer, Gilbert Siame, Loria Siamia, Zanele Sibanda, Claire Sidaway, Seshnag Siddavaram, Nasir Siddique, Sohail Siddique, Nyma Sikondari, Claudia Silva Moniz, Mike Silverstone, Malcolm Sim, Theresa Simangan, Vimbai Simbi, Robert Sime, Oliver Simmons, Richard Simms, Merritt Simon, Natalie Simon, Angela Simpson, Anna Simpson, Danny Simpson, Georgina Simpson, Joanne Simpson, John Simpson, Kerry Simpson, Phillip Simpson, Thomas Simpson, Andrew Simpson, Kathryn Simpson, Cindy Sing, Ankita Singh, Claire Singh, Jayaprakash Singh, Jyoti Singh, Lokeshwar Singh, Manjeet Singh, Nadira Singh, Pankaj Singh, Prabhsimran Singh, Salil Singh, Saurabh Singh, Parag Singhal, Bryan Singizi, Manas Sinha, Utkarsh Sinha, Guy Sisson, Sarah Sithiravel, Karthikadevi Sivakumar, Shanmugasundaram Sivakumar, Darsh Sivakumran, Sivanthi Sivanadarajah, Pasupathy-Rajah Sivasothy, Rebecca Sivers, Alison Sivyer, Nicole Skehan, Robert Skelly, Orlagh Skelton, Imogen Skene, Michael J Skill, Denise Skinner, Tabitha Skinner, Victoria Skinner, Agnieszka Skorko, Iwona Skorupinska, Mariola Skorupinska, Amy Slack, Katie Slack, Wendy Slack, Heather Slade, Helen Slade, Mark Slade, Helen Slater, Lynda Slater, Nicola Slawson, Andrew Sloan, Brendan Sloan, Derek Sloan, Geraldine Sloane, Benjamin Small, Ellen Small, Emma Small, Samuel Small, Karen D Smallshaw, Andy Smallwood, Carien Smit, Aileen Smith, Alex Smith, Amanda Smith, Amy Smith, Andrew Smith, Anna Smith, Camilla Smith, Catherine Smith, Chris Smith, Christopher Smith, Dominic Smith, Eleanor Smith, Harriet Smith, Hazel Smith, Helen Smith, Jacky Smith, Janice Smith, Jessica Smith, Juliet Smith, Karen Smith, Kate Smith, Kathryn Smith, Katie Smith, Kelly Smith, Kerry Smith, Lara Smith, Linda Smith, Lisa Smith, Loren Smith, Maria Smith, Mel Smith, Oliver Smith, Rachel Smith, Rebecca Smith, Richard Smith, Ruth Smith, Sally Smith, Samantha Smith, Stacey Smith, Stephanie Smith, Susan Smith, Imogen Smith, John Smith, Gemma Smithson, Sue Smolen, Sara Smuts, Naoise Smyth, Annette Snell, David Snell, Luke Snell, Beng So, Michelle Soan, Toluleyi Sobande, Alberto Sobrino Diaz, Basit Sohail, Bina Sohail, Herminder Sohal, Roy Soiza, Mary Sokolowski, Olajumoke Solademi, Krishma Solanki, Babak Soleimani, Amanda Solesbury, Reanne Solly, Louise Solomon, Subash Somalanka, Chandrashekaraiah Somashekar, Raj Sonia, Shiu-Ching Soo, Deepti Sood, Pavandeep Soor, Germanda Soothill, Jennifer Soren, Youssef Sorour, Apina Sothinathan, Pragalathan Sothirajah, Najwa Soussi, Donna Southam, David Southern, Iain Southern, Louise Southern, Sara M Southin, Jessica Southwell, Thomas Southworth, Jason Sowter, Claudia Spalding, Enti Spata, Katie Spears, Mark Spears, John Spence, Michelle Spence, Branwell Spencer, Gisele Spencer, Sue Spencer, Tom Spencer, Helen Spicer, Rose Spicer, Helen Spickett, Jennifer Spillane, William Spiller, Kerry Spinks, Michelle Spinks, Nick Spittle, Johanna Sporrer, Karen Spreckley, Janet Spriggs, Oliver Spring, Scott Springworth, Gemma Squires, Jack Squires, Rebecca Squires, Ram Sreenivasan, K Sri Paranthamen, Ramesh Srinivasan, Asha Srirajamadhuveeti, Vino Srirathan, Chloe Stacey, Sybil Stacpoole, Louise Stadon, Tony Staincliffe, Jocasta Staines, Nikki Staines, Katie Stammers, Roxana Stanciu, Grazyna Stanczuk, Helen Stannard, Edward Stanton, Robyn Staples, Simon Stapley, Natalie Staplin, Adam Stark, Michelle Starr, Julie Staves, Rached Stead, Anthea Steel, Charlotte Steel, Conor Steele, John Steer, Vergnano Stefania, Paula Stefanowska, Katie Steinert, Caroline Stemp, Alison Stephens, David Stephensen, Elaine Stephenson, Monique Sterrenburg, Georgia Stevens, Guy Stevens, Melanie Stevens, Will Stevens, Amy Stevenson, Andrew Stevenson, Elaine Stevenson, Lesley Stevenson, Sarah Stevenson, Amanda Stewart, Claire Stewart, Colin Stewart, McKenna Stewart, Rachel Stewart, Rebecca Stewart, Richard Stewart, Jo Stickley, Gemma Stiller, Robert Stirk, Sarah Stirrup, Sarah Stock, Alexander Stockdale, Lynne Stockham, Paul Stockton, Emma Stoddard, Chris Stokes, Ben Stone, Roisin Stone, Sarah Stone, Imogen Storey, Kim Storton, Frederick Stourton, Angela Strachan, Catherine Strait, Ellen Strakosch, Emma Stratton, Jane Stratton, Sam Straw, Luke Streeter, Dieter Streit, Emma Stride, Sally Stringer, Sophia Strong-Sheldrake, Siske Struik, Carmel Stuart, Anna Stubbs, Harrison Stubbs, Ann Sturdy, Sharon Sturney, Matt Stuttard, Cristina Suarez, Karuna Subba, Christian P Subbe, Manjula Subramanian, Venkatram Subramanian, Chinari Subudhi, Rebecca Suckling, Srivatsan Sudershan, Lee Sudlow, Gayle Sugden, Peter Sugden, Rudresh Sukla, Ali Suliman, Fatimah Suliman, Ian Sullivan, Sugrah Sultan, Jennifer Summers, Mark Summerton, Samyukta Sundar, Reka Sundhar, Edmond Sung, Nadia Sunni, Jay Suntharalingam, Amitava Sur, Dharmic Suresh, Shilpa Suresh, Rachel Suri, Michael Surtees, Danielle Suter, Helen Sutherland, Rachel Sutherland, Rebecca Sutherland, Dovile Sutinyte, Deborah Sutton, John Sutton, Sam Sutton, Mihaela Sutu, Marie-Louise Svensson, Sima Svirpliene, Andrew Swain, Thomas Swaine, Christopher Swales, Lorna Swan, Nicola Swarbrick, Tirion Swart, Stephen Sweetman, Samaher Sweity, Ealish Swift, Paul Swift, Pauline Swift, Peter Swift, Rachael Swift, Rachel Swingler, Sophie Swinhoe, Katarzyna Swist-Szulik, Luke Swithenbank, Omair Syed, Catriona Sykes, Daisy Sykes, Eliot Sykes, Luke Sylvester, Dominic Symon, Andrew Syndercombe, Zoe Syrimi, Jen Syson, Gemma Szabo, Tamas Szakmany, Megan Szekely, Matthew Szeto, Maria Tadros, Amr Tageldin, Lucy Tague, Hasan 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Caroline Tee, Rajni Tejwani, Seble Tekle, Adam Telfer, Vibha Teli, Jennifer Tempany, Holly Templar, Julie Temple, Natalie Temple, Helen Tench, Yi He Teoh, Lynne Terrett, Louise Terry, Abbi Tervit, Dariusz Tetla, Kate Tettmar, Shirish Tewari, Daniel Tewkesbury, Joana Texeira, ChiaLing Tey, Clare Thakker, Manish Thakker, Amirtharajh Tharmakulasingam, Hilary Thatcher, Andrew Thayanandan, Krishna Thazhatheyil, Eaint Thein, Lambrini Theocharidou, Phyu Thet, Kapeendran Thevarajah, Mayooran Thevendra, Nang Thiri Phoo, Yvette Thirlwall, Muthu Thirumaran, Alice Thomas, Andrew Thomas, Caradog Thomas, Emma Thomas, Enson Thomas, Esther Thomas, Hannah Thomas, Helen Thomas, James Thomas, Karen Thomas, Koshy Thomas, Lucy Thomas, Rachel Thomas, Rebecca Thomas, Rhys Thomas, Ruth Thomas, Samantha Thomas, Sarah Thomas, Sherine Thomas, Tessy Thomas, Vicky Thomas, Rhian Thomas-Turner, Samantha Thomas-Wright, Catherine Thompson, Christopher Thompson, Clara Thompson, Fiona Thompson, Katharine Thompson, Laura Thompson, Liz Thompson, Luke Thompson, Michael Thompson, Orla Thompson, Rebecca Thompson, Roger Thompson, Trevor Thompson, Usilla Thompson, Nicola Thomson, Natasha Thorn, Charlotte Thorne, Nicola Thorne, Wendy Thorne, Jim Thornton, Michael Thornton, Richard Thornton, Sara Thornton, Susan Thornton, Thomas Thornton, Tracey Thornton, Allison Thorpe, Christopher Thorpe, Sarah Thorpe, Paradeep Thozthumparambil, Laura Thrasyvoulou, Hannah Thraves, Elisha Thuesday, Vicky Thwaiotes, Guy Thwaites, Simon Tiberi, Jane Tidman, Serena Tieger, Carey Tierney, Caroline Tierney, Mark Tighe, Sorrell Tilbey, Amanda Tiller, John Timerick, Elizabeth Timlick, Alison Timmis, Hayley Timms, Anne-Marie Timoroksa, Samakomva Tinashe, Heather Tinkler, Marianne Tinkler, Jacqui Tipper, Helen Tivenan, Helen T-Michael, Anne Todd, Jackie Todd, Stacy Todd, Mohamed Tohfa, Helena Tollick, Melanie Tolson, Ana Luisa Tomas, Natalia Tomasova, Sharon Tomlin, Simon Tomlins, Jo Tomlinson, James Tonkin, Ivan Tonna, Catherine Toohey, Kirsty Topham, Mathew Topping, Ruhaif Tousis, Peter Tovey, Gareth Towersey, Jason Towler, Jill Townley, Alain Townsend, Chris Townsend, Richard Tozer, Claire Tranter, Helen Tranter, Jonathan Trattles, Christopher Travill, Sarah Traynor, Karis Treuberg, Mike Trevett, Ascanio Tridente, Sanchia Triggs, Fiona Trim, Thomas Trimble, Alex Trimmings, Tom Trinick, Sven Troedson, Emily Tropman, Amy Trotter, Madeleine Trowsdale Stannard, Nigel Trudgill, Maria Truslove, Shaun Trussell, Tariq Trussell, Sara Tryon, Kyriaki Tsakiridou, Christine Tsang, Hoi Pat Tsang, Peter Tsang, Tan Tsawayo, Kyriaki Karali Tsilimpari, Georgios Tsinaslanidis, Simon Tso, Sally Tucker, Victoria Tuckley, Caroline Tuckwell, Aisha Tufail, Redmond Tully, Grace Tunesi, Saidat Turawa, Killiam Turbitt, Anna Turco, Krystyna Turek, Rezon Turel, Tolga Turgut, Claudia Turley, Alison Turnbull, Aine Turner, Ash Turner, Charlotte Turner, David Turner, Frances Turner, Gail Turner, Kate Turner, Kelly Turner, Louise Turner, Lucy Turner, Marc Turner, Mark Turner, Patricia Turner, Ruth Turner, Sally Turner, Samantha Turner, Susan Turner, Victoria Turner, Sharon Turney, Jon Turvey, Conor Tweed, David Tweed, Rebecca Twemlow, Emma Twohey, Bhavya Tyagi, Vedang Tyagi, Abigail Tyer, Jayne Tyler, Jennifer Tyler, Alison Tyzack, Petros Tzavaras, Mohammad S Uddin, Ruhama Uddin, Ruzena Uddin, Salamat Ullah, Sana Ullah, Sanda Ullah, Athavan Umaipalan, Judith Umeadi, Akudo Umeh, Wilfred Umeojiako, Ben Ummat, Charlotte Underwood, Jonathan Underwood, Laura Unitt, Adam Unsworth, Jasvinder Uppal, Veerpal S Uppal, James Uprichard, Gerry Upson, Masood Ur Rasool, Alison Uriel, Sebastian Urruela, Hiromi Uru, Miranda Usher, Rebecca Usher, Alex UsherRea, Andrew Ustianowski, Jane Uttley, Linda C Vaccari, Uddhav Vaghela, Abhay Vaidya, Bernardas Valecka, Jennifer Valentine, Balan Valeria, Pramodh Vallabhaneni, Pedro Valle Vallines, Luke Vamplew, Ekaterini Vamvakiti, Joannis Vamvakopoulos, Maud van de Venne, Alex van der Meer, Nora van der Stelt, Joseph Vance-Daniel, Rama Vancheeswaran, Caryn Vander Riet, Samuel I Vandeyoon, Padma Vankayalapati, Piyush Vanmali, Chloe Vansomeren, William Van't Hoff, Sejal Vara, Kate Vardigans, Stehen J Vardy, Anu Varghese, Maria Varghese, William Varney, Giulia Varnier, Valeria Vasadi, Olivia Vass, Vimal Vasu, Vasanthi Vasudevan, Manu Vatish, Heloyes Vayalaman, Christopher Vaz, Niki Veale, Sachuda Veerasamy, Bar Velan, Swati Velankar, Luxmi Velauthar, Neyme Veli, Nicola Vella, Anitha Velusamy, Ian Venables, Mavi Venditti, David Veniard, Ramya Venkataramakrishnan, Richard Venn, Robert Venn, Lyn Ventilacion, Joanne Vere, Mark Veres, Stefania Vergnano, Will Verling, Amit Verma, Rachel Vernall, Britney Vernon, Mark Vertue, Jerik Verula, Natalie Vethanayagam, Lucy Veys, Carinna Vickers, Saji Victor, Jennifer Vidler, Wayne Vietri, Bavithra Vijayakumar, Vinod Warrier Vijayaraghavan Nalini, Brigita Vilcinskaite, Neringa Vilimiene, Sudharkar Vimalanathan, Lynn Vinall, Sylvia Vinay, Latha Vinayakarao, Rachel Vincent, Rosie Vincent, Pritpal Virdee, Emma Virgilio, Abdullah M Virk, Elisa Visentin, Jeyakumar Visuvanathan, Karunakaran Vithian, Sorice Vittoria, Elena Vlad, Ben Vlies, Alain Vuylsteke, Eleftheria Vyras, Richard Wach, Beverley Wadams, Susan Wadd, Natalia Waddington, Kirsten Wadsworth, Syed EI Wafa, Daniel Wagstaff, Lynda Wagstaff, Dalia Wahab, Zaroug Wahbi, Abiodun Waheed Adigun, Sawan Waidyanatha, Rachel Wake, Alice Wakefield, William Wakeford, Michelle Wakelin, Fiona Wakinshaw, Andrew Walden, Jane Walden, Lorna Walding, Alexandria Waldron, Gemma Walker, Harriet Walker, Ian Walker, Jasmine Walker, Kevin Walker, Kim Walker, Linda Walker, Marie T Walker, Olivia Walker, Rachel Walker, Rebecca Walker, Susan Walker, Derek Wallbank, Rebecca Wallbutton, Jessica Wallen, Karl Wallendszus, Arabella Waller, Fiona Waller, Rosemary Waller, Gabiel Wallis, Gabriel Wallis, Louise Wallis, Donna Walsh, Elizabeth Walsh, Livia Walsh, Deborah Walstow, Daniel Walter, Alex Walters, Holt Walters, James Walters, Jocelyn Walters, Eileen Walton, Lucy Walton, Olivia Walton, Sharon Walton, Susan Walton, Mandy Wan, Thin Wan, Mary Wands, Rachel Wane, Frank Wang, Nick Wang, Ran Wang, Deborah Warbrick, Samantha Warburton, Deborah Ward, Emma Ward, Joanna Ward, Karen Ward, Luke Ward, Nicola Ward, Rachael Ward, Rebecca Ward, Thomas Ward, Tom Ward, Scott A Warden, Adele Wardle, Karen Wardle, Steve Wardle, Hassan Wardy, Scott Waring, Jenny Warmington, Ben Warner, Christian Warner, Lewis Warnock, Sarah Warran, Jade Warren, Lisa Warren, Yolanda Warren, Hannah Warren-Miell, Gill Warwick, Charlotte Washington, Helen Wassall, Hazel J Watchorn, Holly Waterfall, Abby Waters, Donald Waters, Mark Waterstone, Catherine Watkins, Catrin Watkins, Eleanor Watkins, Karen Watkins, Lynn Watkins, Nick Watkins, Abigail Watson, Adam JR Watson, Ekaterina Watson, Eleanor Watson, Paul Watson, Rebecca Watson, Robert Watson, Sandra Watson, Malcolm Watters, Donna Watterson, Daniel Watts, John Watts, Merlin Watts, Victoria Waugh, Emma Wayman, Akhlaq Wazir, Mark Weatherhead, Nick Weatherly, Paul Weaver, Hayley Webb, Kathryn Webb, Kylie Webb, Stephen Webb, Cheryl Websdale, Deborah Webster, Ian Webster, Tim Webster, Kathleen Wedgeworth, Ling Wee, Rebecca Weerakoon, Thanuja Weerasinghe, Janaka Weeratunga, Maria Weetman, Shuying Wei, Immo Weichert, Hugh Welch, James Welch, Leanne Welch, Steven Welch, Samantha Weller, Lucy Wellings, Brian Wells, Susan Wellstead, Berni Welsh, Richard Welsh, Ingeborg Welters, Rachael Welton, Lauren Wentworth, Kate Wesseldine, James Wesson, Jim Wesson, Adam West, Magdelena West, Raha West, Ruth West, Sophie West, Luke Western, Ruth Westhead, Heather Weston, Alice Westwood, Bill Wetherill, Sharon Wheaver, Helen Wheeler, Ben Whelan, Matthew Whelband, Amanda Whileman, Alison Whitcher, Abbie White, Andrew White, Benjamin White, Christopher White, Duncan White, Emily White, James White, Jonathan White, Katie White, Marie White, Nick White, Sarah White, Sonia White, Stephen White, Tracey White, Catherine Whitehead, Anne Whitehouse, Claire Whitehouse, Tony Whitehouse, Julia Whiteley, Sophie Whiteley, Victoria Whiteside, Drew Whitley, Kaitlyn Whitley, Gabriel Whitlingum, David Whitmore, Elizabeth Whittaker, Lindsay Whittam, Andrew Whittingham Hirst, Ashley Whittington, Helen Whittle, Robert Whittle, Suzanne Whyte, Eunice Wiafe, Lou Wiblin, John Widdrington, Jason Wieboldt, Hannah Wieringa, Cornelia Wiesender, Laura Wiffen, Andrew Wight, Christopher Wignall, Danielle Wilcock, Emma Wilcock, Louise Wilcox, Laura Wild, Stephen Wild, Michael Wilde, Peter Wilding, Ritchie Wildman, Tracey Wildsmith, Joe Wileman, Donna Wiles, Joy Wiles, Kate Wiles, Elva Wilhelmsen, Thomas Wiliams, Chloe Wilkes, Janet Wilkie, David Wilkin, Hannah Wilkins, Joy Wilkins, Suzanne Wilkins, Helen Wilkinson, Holly Wilkinson, Iain Wilkinson, Lesley Wilkinson, Martin Wilkinson, Nicola Wilkinson, Sophia Wilkinson, Susan Wilkinson, Tim Wilkinson, Sylvia Willetts, Aimee Williams, Alexandra Williams, Alison Williams, Angharad Williams, Ava Williams, Carl Williams, Caroline V Williams, Claire Williams, Dewi Williams, Gail Williams, Gemma Williams, Gina Williams, Hannah Williams, James Williams, Jayne Williams, Jennie Williams, John Williams, Joseph Williams, Karen Williams, Kathryn Williams, Marie Williams, Matthew Williams, Patricia Williams, Penny Williams, Rachael Williams, Rupert Williams, Samson Williams, Sarah Williams, Sophie Williams, Tamanna Williams, Annie Williamson, Cath Williamson, Catherine Williamson, Dawn Williamson, James D Williamson, Rachel Williamson, Helen Williamson, Bruce Willian, Elizabeth Willis, Emily Willis, Heather Willis, Herika Willis, Joanna Willis, Laura Willmott, Louise Wills, Lucy Willsher, Catherine Willshire, Francesca Willson, Alison Wilson, Andrea Wilson, Antoinette Wilson, Billy Wilson, Catherine Wilson, Eve Wilson, James Wilson, Karen Wilson, Kate Wilson, Lucinda Wilson, Mark Wilson, Matthew Wilson, Toni Wilson, Evie Wiltsher, Marlar Win, Tin Win, Wut Yee Win Win, Lucinda Winckworth, Laura Winder, Piers Winder, Phillip Windrum, Kerry Winham-Whyte, Helen Winmill, Simon Winn, Carmen Winpenny, Helen Winslow, Helen Winter, Jonathan Winter, Pascal Winter, Barbara Winter-Goodwin, Stephen Wisdom, Matthew Wise, Martin Wiselka, Rebecca Wiseman, Sophie Wiseman, Steven Wishart, Holly Wissett, Eric Witele, Nicholas Withers, Janet Wittes, Donna Wixted, Therese Wodehouse, Will Wolf, Nicola Wolff, Kirsten Wolffsohn, Rebecca Wolf-Roberts, Magda Wolna, Elena Wolodimeroff, Adam Wolstencroft, Alan Wong, Charlotte Wong, Chi-Hung Wong, Edwin Wong, Jessica Sue Yi Wong, Kit Y Wong, Lee Wong, Mei Yin Wong, Nick Wong, Sam Wong, Yun Man Wong, Amanda Wood, Caroline Wood, Carrie Anne Wood, Dianne Wood, Fiona Wood, Hannah Wood, Jennifer Wood, Joe Wood, Julia Wood, Kathryn Wood, Lisa Wood, Louise Wood, Michelle Wood, Stephen Wood, Tracy Wood, Ursula Wood, Katharine Woodall, Rebecca Woodfield, Christopher Woodford, Elizabeth Woodford, Jill Woodford, Luke Woodford, Louise Woodhead, Timothy Woodhead, Philip Woodland, Marc Woodman, Debra Woods, Jane Woods, Katherine Woods, Sarah Woods, Zoe Woodward, Rachel Wookey, Megan Woolcock, Gemma Wooldridge, Rebecca Woolf, Chris Woollard, Christopher Woollard, Louisa Woollen, Emma Woolley, Jade Woolley, Daniel Woosey, Dan Wootton, Joanne Wootton, Daniel Worley, Stephy Worton, Jonathan Wraight, Maria Wray, Tim Wreford-Bush, Joanne Wren, Kim Wren, Lynn Wren, Caroline Wrey Brown, Catherine Wright, Demi Wright, Francesca Wright, Imogen Wright, Lee Wright, Lianne Wright, Pete Wright, Rachel Wright, Rebecca Wright, Stephanie Wright, Tim Wright, Caroline Wroe, Hannah Wroe, Henry Wu, Peishan Wu, Pensee Wu, Jonathan Wubetu, Retno Wulandari, Craig Wyatt, Frederick Wyn-Griffiths, Inez Wynter, Bindhu Xavier, Arnold Xhikola, Zhongyang Xia, Huiyuan Xiao, Masseh Yakubi, May Yan, Freda Yang, Yingjia Yang, Michael Yanney, Woei Lin Yap, Nabil Yaqoob, Naairah Yaqub, Salima Yasmin, Bryan Yates, David Yates, Edward Yates, Helen Yates, Julie Yates, Mark Yates, Charlotte Yearwood Martin, Andrew Yeatman, Khin Yein, Fiona Yelnoorkar, Peter Yew, Kawai Yip, Laura Ylquimiche, Laura Ylquimiche Melly, Inez Ynter, H Yong, Jemma Yorke, Jasmine Youens, Abdel Younes Ibrahim, Eoin Young, Gail Young, Louise Young, Richard Young, Asfand Yousafzar, Sajeda Youssouf, Ahmed Yousuf, Chrissie Yu, Bernard Yung, Daniel Yusef, Said Yusef, Intekhab Yusuf, Anna-Sophia Zafar, Silvia Zagalo, Su Zaher, Aqsa Zahoor, Kareem Zaki, Nabhan Zakir, Kasia Zalewska, Ane Zamalloa, Mohsin Zaman, Raisa Zaman, Shakir Zaman, Julie Zamikula, Louise Zammit, Marie Zammit-Mangion, Lynn Zarb, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Marian Zelman, Xiaobei Zhao, Dongling Zheng, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei Thankt Zin, Veronica Zindonda, Eleanor Zinkin, Vivian Zinyemba, Christos Zipitis, Arkadiusz Zmierczak, Azam Zubir, Roslin Zuha, Naz Zuhra, Rasha Zulaikha, Sabrina Zulfikar, Carol Zullo, Ana Zuriaga-Alvaro, Will Zuurbier, Sheba Zyengi, and University of St Andrews. School of Medicine
Subjects: Male, Convalescent plasma, medicine.medical_treatment, 030204 cardiovascular system & hematology, Antibodies, Viral, Rate ratio, 0302 clinical medicine, RA0421, RA0421 Public health. Hygiene. Preventive Medicine, Medicine, Hospital Mortality, 030212 general & internal medicine, 11 Medical and Health Sciences, Aged, 80 and over, Medicine(all), Mortality rate, Covid19, Articles, 3rd-DAS, General Medicine, Middle Aged, Hospitals, Treatment Outcome, Female, Open label, Coronavirus Infections, Life Sciences & Biomedicine, RM, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), 03 medical and health sciences, Medicine, General & Internal, SDG 3 - Good Health and Well-being, General & Internal Medicine, Internal medicine, Humans, In patient, Pandemics, COVID-19 Serotherapy, Aged, Mechanical ventilation, Science & Technology, SARS-CoV-2, business.industry, Significant difference, Immunization, Passive, COVID-19, Length of Stay, NIS, R1, Respiration, Artificial, United Kingdom, RM Therapeutics. Pharmacology, RECOVERY Collaborative Group, business
Abstract: Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.
Published: 2021

43. Tibial tray debonding from the cement mantle is associated with deformation of the backside of polyethylene tibial inserts

Author: Moreica B. Pabbruwe, Thomas J. Joyce, Antoni V.F. Nargol, Nish Shyam, Stephen R. Wells, David J. Langton, Rohan M. Bhalekar, Ryan Collier, and Matthew E. Nargol
Subjects: Adult, Male, Total knee arthroplasty, Deformation (meteorology), Prosthesis Design, Total knee, chemistry.chemical_compound, Cement mantle, Humans, Medicine, Orthopedics and Sports Medicine, Composite material, Arthroplasty, Replacement, Knee, Device Removal, Aged, Aged, 80 and over, Cement, Tibial tray, business.industry, Bone Cements, Middle Aged, Polyethylene, Prosthesis Failure, chemistry, Regression Analysis, Female, Surgery, Knee Prosthesis, business
Abstract: Aims The aim of this study was to investigate whether wear and backside deformation of polyethylene (PE) tibial inserts may influence the cement cover of tibial trays of explanted total knee arthroplasties (TKAs). Methods At our retrieval centre, we measured changes in the wear and deformation of PE inserts using coordinate measuring machines and light microscopy. The amount of cement cover on the backside of tibial trays was quantified as a percentage of the total surface. The study involved data from the explanted fixed-bearing components of four widely used contemporary designs of TKA (Attune, NexGen, Press Fit Condylar (PFC), and Triathlon), revised for any indication, and we compared them with components that used previous generations of PE. Regression modelling was used to identify variables related to the amount of cement cover on the retrieved trays. Results A total of 114 explanted fixed-bearing TKAs were examined. This included 76 used with contemporary PE inserts which were compared with 15 used with older generation PEs. The Attune and NexGen (central locking) trays were found to have significantly less cement cover than Triathlon and PFC trays (peripheral locking group) (p = 0.001). The median planicity values of the PE inserts used with central locking trays were significantly greater than of those with peripheral locking inserts (205 vs 85 microns; p < 0.001). Attune and NexGen inserts had a characteristic pattern of backside deformation, with the outer edges of the PE deviating inferiorly, leaving the PE margins as the primary areas of articulation. Conclusion Explanted TKAs with central locking mechanisms were significantly more likely to debond from the cement mantle. The PE inserts of these designs showed characteristic patterns of deformation, which appeared to relate to the manufacturing process and may be exacerbated in vivo. This pattern of deformation was associated with PE wear occurring at the outer edges of the articulation, potentially increasing the frictional torque generated at this interface. Cite this article: Bone Joint J 2021;103-B(12):1791–1801.
Published: 2021

44. Participants Switching to Second-Line Antiretroviral Therapy with Susceptible Virus Display Inferior Adherence and Worse Outcomes: An Observational Analysis

Author: Lentlametse Mantshonyane, Michael J. Levy, Jason Roy, Kathrine Bar, Alberto M. LaRosa, Xin Sun, Robert E. Gross, Catherine Godfrey, Lu Zheng, Ann C. Collier, and Carole L. Wallis
Subjects: Adult, Male, medicine.medical_specialty, Anti-HIV Agents, Observational analysis, Human immunodeficiency virus (HIV), Medication adherence, HIV Infections, Drug resistance, medicine.disease_cause, Virus, Second line, Acquired immunodeficiency syndrome (AIDS), Antiretroviral Therapy, Highly Active, Internal medicine, medicine, Humans, Treatment Failure, business.industry, Clinical and Epidemiologic Research, Public Health, Environmental and Occupational Health, Viral Load, medicine.disease, Antiretroviral therapy, Infectious Diseases, Anti-Retroviral Agents, HIV-1, business
Abstract: Evidence on the impact of human immunodeficiency virus (HIV) drug resistance on regimens following treatment failure is varied and inconclusive. Differential medication adherence may explain this variation. We aimed to test the association between drug resistance at first-line antiretroviral therapy (ART) switch and adherence to and virologic failure on subsequent ART. We conducted a secondary analysis of data from an open-labeled randomized trial of second-line ART (ACTG A5234). ART susceptibility was determined from study entry plasma using the Stanford Drug Resistance database version 8.7. Adherence was measured with microelectronic monitors. Three adherence variables and rates of virologic failure (HIV-1 RNA ≥1000 copies/mL) on second-line ART were compared between participants with and without resistance at first-line ART failure. Of 214 participants switching to second-line ART with baseline resistance results, 113 (53%) were men, mean age was 39 years (standard deviation 10.3), and 37 (17%) had susceptible virus at study entry. Cumulative genotypic susceptibility score (cGSS) was inversely associated with adherence, adjusted odds ratio (aOR) 0.15, 95% confidence interval (CI) (0.05–0.40), p
Published: 2021

45. Telomeres are shorter and associated with number of suicide attempts in affective disorders

Author: Srdjan Djurovic, Daniel Quintana, Viktoria Birkenæs, Marit Haram, Maren Caroline Frogner Werner, Margrethe Collier Høegh, Ingrid Agartz, Synve Hoffart Lunding, Carmen Martin-Ruiz, Torbjørn Elvsåshagen, Nils Eiel Steen, Ole A. Andreassen, Lars T. Westlye, and Monica Aas
Subjects: Clinical interview, Oncology, Depressive Disorder, Major, medicine.medical_specialty, Mood Disorders, business.industry, Longitudinal data, Suicide, Attempted, Telomere, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Distress, Internal medicine, Humans, Medicine, Major depressive disorder, Biomarker (medicine), In patient, business, Telomere Shortening
Abstract: Shorter telomere length is a putative biomarker of accelerated aging and has been associated with affective disorders and mortality. Psychological factors and behaviors associated with telomere shortening are yet to be clarified. Here, we investigate the association between history of suicide attempts and telomere length in patients with affective disorders.Leucocyte telomere length was determined by quantitative real-time Polymerase Chain Reaction (qPCR) in patients with affective disorders (n = 248) including bipolar disorders type I (n = 159), type II (n = 67), major depressive disorder (n = 22), and healthy controls (n = 401). Diagnosis, duration of illness, and age at onset were assessed using the Structural Clinical Interview for DSM-IV (SCID-I). Number of lifetime suicide attempts were based on self-reports. Effect size was calculated using Cohen's d.Telomere length was reduced in patients with affective disorders relative to healthy controls (d = 0.18, F = 5.26, p = 0.02). Among patients, a higher number of suicide attempts was associated with shorter telomere length (β = -0.24, t = -3.83, CI = -0.44 to -0.14, p 0.001), also when controlling for duration of illness and age at onset (β = -.23, CI = -.42 to -.12, p = 0.001). Multiple suicide attempts were associated with telomere length reduction comparable to eight years lifespan, adjusted for demographic and clinical characteristics.While longitudinal data are needed to clarify the temporal course, previous suicide attempts and related distress may accelerate telomere shortening and aging in patients with affective disorders.
Published: 2021

46. Evaluation of predicted Medfly (Ceratitis capitata) quarantine length in the United States utilizing degree-day and agent-based models [version 2; referees: 2 approved, 1 approved with reservations]

Author: Travis Collier and Nicholas Manoukis
Subjects: Epidemiology, Statistical Methodologies & Health Informatics, Medicine, Science
Abstract: Invasions by pest insects pose a significant threat to agriculture worldwide. In the case of Ceratitis capitata incursions on the US mainland, where it is not officially established, repeated detections are followed by quarantines and treatments to eliminate the invading population. However, it is difficult to accurately set quarantine duration because non-detection may not mean the pest is eliminated. Most programs extend quarantine lengths past the last fly detection by calculating the amount of time required for 3 generations to elapse under a thermal unit accumulation development model (“degree day”). A newer approach is to use an Agent-Based Simulation (ABS) to explicitly simulate population demographics and elimination. Here, predicted quarantine lengths for 11 sites in the continental United States are evaluated using both approaches. Results indicate a strong seasonality in quarantine length, with longer predictions in the second half of the year compared with the first; this pattern is more extreme in degree day predictions compared with ABS. Geographically, quarantine lengths increased with latitude, though this was less pronounced under the ABS. Variation in quarantine lengths for particular times and places was dramatically larger for degree day than ABS, generally spiking in the middle of the year for degree day and peaking in second half of the year for ABS. Analysis of 34 C. capitata quarantines from 1975 to 2017 in California shows that, for all but two, quarantines were started in the second half of the year, when degree day quarantine lengths are longest and have the highest uncertainty. For a set of hypothetical outbreaks based on these historical quarantines, the ABS produced significantly shorter quarantines than degree day calculations. Overall, ABS quarantine lengths were more consistent than degree day predictions, avoided unrealistically long values, and captured effects of rare events such as cold snaps.
Published: 2018
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47. Single-cell transcriptomics reveals a new dynamical function of transcription factors during embryonic hematopoiesis

Author: Isabelle Bergiers, Tallulah Andrews, Özge Vargel Bölükbaşı, Andreas Buness, Ewa Janosz, Natalia Lopez-Anguita, Kerstin Ganter, Kinga Kosim, Cemre Celen, Gülce Itır Perçin, Paul Collier, Bianka Baying, Vladimir Benes, Martin Hemberg, and Christophe Lancrin
Subjects: Stem Cells, transcription factors, developmental biology, Medicine, Science, Biology (General), QH301-705.5
Abstract: Recent advances in single-cell transcriptomics techniques have opened the door to the study of gene regulatory networks (GRNs) at the single-cell level. Here, we studied the GRNs controlling the emergence of hematopoietic stem and progenitor cells from mouse embryonic endothelium using a combination of single-cell transcriptome assays. We found that a heptad of transcription factors (Runx1, Gata2, Tal1, Fli1, Lyl1, Erg and Lmo2) is specifically co-expressed in an intermediate population expressing both endothelial and hematopoietic markers. Within the heptad, we identified two sets of factors of opposing functions: one (Erg/Fli1) promoting the endothelial cell fate, the other (Runx1/Gata2) promoting the hematopoietic fate. Surprisingly, our data suggest that even though Fli1 initially supports the endothelial cell fate, it acquires a pro-hematopoietic role when co-expressed with Runx1. This work demonstrates the power of single-cell RNA-sequencing for characterizing complex transcription factor dynamics.
Published: 2018
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48. Correction: Baseline Omega-3 Index Correlates with Aggressive and Attention Deficit Disorder Behaviours in Adult Prisoners.

Author: Barbara J Meyer, Mitchell K Byrne, Carole Collier, Natalie Parletta, Donna Crawford, Pia C Winberg, David Webster, Karen Chapman, Gayle Thomas, Jean Dally, Marijka Batterham, Ian Farquhar, Anne-Marie Martin, and Luke Grant
Subjects: Medicine, Science
Abstract: [This corrects the article DOI: 10.1371/journal.pone.0120220.].
Published: 2018
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49. A proof-of-concept study applying machine learning methods to putative risk factors for eating disorders: results from the multi-centre European project on healthy eating

Author: Jake Linardon, Janet Treasure, Christopher J Greenwood, George J. Youssef, Kate Tchanturia, M. Anderluh, Sandro Sorbi, Andreas Karwautz, David A. Collier, Benedetta Nacmias, Fernando Fernández-Aranda, Valdo Ricca, Laura Bellodi, Gudrun Wagner, Matthew Fuller-Tyszkiewicz, and Isabel Krug
Subjects: Bulimia nervosa, business.industry, medicine.disease, Logistic regression, Machine learning, computer.software_genre, Regression, Psychiatry and Mental health, Eating disorders, Lasso (statistics), Anorexia nervosa (differential diagnoses), medicine, Artificial intelligence, Medical diagnosis, Risk factor, business, computer, Applied Psychology
Abstract: Background Despite a wide range of proposed risk factors and theoretical models, prediction of eating disorder (ED) onset remains poor. This study undertook the first comparison of two machine learning (ML) approaches [penalised logistic regression (LASSO), and prediction rule ensembles (PREs)] to conventional logistic regression (LR) models to enhance prediction of ED onset and differential ED diagnoses from a range of putative risk factors. Method Data were part of a European Project and comprised 1402 participants, 642 ED patients [52% with anorexia nervosa (AN) and 40% with bulimia nervosa (BN)] and 760 controls. The Cross-Cultural Risk Factor Questionnaire, which assesses retrospectively a range of sociocultural and psychological ED risk factors occurring before the age of 12 years (46 predictors in total), was used. Results All three statistical approaches had satisfactory model accuracy, with an average area under the curve (AUC) of 86% for predicting ED onset and 70% for predicting AN v. BN. Predictive performance was greatest for the two regression methods (LR and LASSO), although the PRE technique relied on fewer predictors with comparable accuracy. The individual risk factors differed depending on the outcome classification (EDs v. non-EDs and AN v. BN). Conclusions Even though the conventional LR performed comparably to the ML approaches in terms of predictive accuracy, the ML methods produced more parsimonious predictive models. ML approaches offer a viable way to modify screening practices for ED risk that balance accuracy against participant burden.
Published: 2021

50. Schizophrenia is defined by cell-specific neuropathology and multiple neurodevelopmental mechanisms in patient-derived cerebral organoids

Author: Michael Notaras, Dilek Colak, Aiman Lodhi, Paul Collier, Hagen Tilgner, David W. Greening, Friederike Dündar, and Nicole M. Sayles
Subjects: biology, Neurogenesis, Neuropathology, Human brain, Cellular and Molecular Neuroscience, Psychiatry and Mental health, medicine.anatomical_structure, biology.protein, Organoid, medicine, Progenitor cell, Induced pluripotent stem cell, Molecular Biology, Neuroscience, Neurotrophin, Progenitor
Abstract: Due to an inability to ethically access developing human brain tissue as well as identify prospective cases, early-arising neurodevelopmental and cell-specific signatures of Schizophrenia (Scz) have remained unknown and thus undefined. To overcome these challenges, we utilized patient-derived induced pluripotent stem cells (iPSCs) to generate 3D cerebral organoids to model neuropathology of Scz during this critical period. We discovered that Scz organoids exhibited ventricular neuropathology resulting in altered progenitor survival and disrupted neurogenesis. This ultimately yielded fewer neurons within developing cortical fields of Scz organoids. Single-cell sequencing revealed that Scz progenitors were specifically depleted of neuronal programming factors leading to a remodeling of cell-lineages, altered differentiation trajectories, and distorted cortical cell-type diversity. While Scz organoids were similar in their macromolecular diversity to organoids generated from healthy controls (Ctrls), four GWAS factors (PTN, COMT, PLCL1, and PODXL) and peptide fragments belonging to the POU-domain transcription factor family (e.g., POU3F2/BRN2) were altered. This revealed that Scz organoids principally differed not in their proteomic diversity, but specifically in their total quantity of disease and neurodevelopmental factors at the molecular level. Single-cell sequencing subsequently identified cell-type specific alterations in neuronal programming factors as well as a developmental switch in neurotrophic growth factor expression, indicating that Scz neuropathology can be encoded on a cell-type-by-cell-type basis. Furthermore, single-cell sequencing also specifically replicated the depletion of BRN2 (POU3F2) and PTN in both Scz progenitors and neurons. Subsequently, in two mechanistic rescue experiments we identified that the transcription factor BRN2 and growth factor PTN operate as mechanistic substrates of neurogenesis and cellular survival, respectively, in Scz organoids. Collectively, our work suggests that multiple mechanisms of Scz exist in patient-derived organoids, and that these disparate mechanisms converge upon primordial brain developmental pathways such as neuronal differentiation, survival, and growth factor support, which may amalgamate to elevate intrinsic risk of Scz.
Published: 2021

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