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1. Desmopressin for prevention of bleeding for thrombocytopenic, critically ill patients undergoing invasive procedures: A randomised, double‐blind, placebo‐controlled feasibility trial

Author: Michael J. R. Desborough, Emma Laing, Daphne Kounali, Ana Mora, Renate Hodge, Siobhan Martin, Helen Thomas, Cara Hudson, Joseph Parsons, Akshay Shah, Paula Hutton, Tim Parke, Matthew P. Wise, Matthew Morgan, Stuart McKechnie, and Simon J. Stanworth
Subjects: bleeding disorders, desmopressin, thrombocytopenia, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Abstract Thrombocytopenic patients have an increased risk of bleeding when undergoing invasive procedures. In a multicentre, phase II, blinded, randomised, controlled feasibility trial, critically ill patients with platelet count 100 × 109/L or less were randomised 1:1 to intravenous desmopressin (0.3 µg/kg) or placebo before an invasive procedure. Forty‐three participants (18.8% of those eligible) were recruited, with 41 eligible for analysis. Post‐procedure bleeding occurred in one of 22 (4.5%) in the placebo arm and zero of 19 in the desmopressin arm. Despite liberal inclusion criteria, there were significant feasibility challenges recruiting patients in the critical care setting prior to invasive procedures.
Published: 2024
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2. Doppler ultrasound surveillance of recently formed haemodialysis arteriovenous fistula: the SONAR observational cohort study

Author: James Richards, Dominic Summers, Anna Sidders, Elisa Allen, Mohammed Ayaz Hossain, Subhankar Paul, Matthew Slater, Matthew Bartlett, Regin Lagaac, Emma Laing, Valerie Hopkins, Chloe Fitzpatrick-Creamer, Cara Hudson, Joseph Parsons, Samuel Turner, Andrew Tambyraja, Subash Somalanka, James Hunter, Sam Dutta, Neil Hoye, Sarah Lawman, Tracey Salter, Mohammed Farid Aslam, Atul Bagul, Rajesh Sivaprakasam, George E Smith, Helen L Thomas, Zia Moinuddin, Simon R Knight, Nicholas Barnett, Reza Motallebzadeh, and Gavin J Pettigrew
Subjects: arteriovenous fistula, renal dialysis, ultrasonography, doppler, kidney failure, chronic: haemodialysis, vascular access surgery, feasibility studies, observational cohort study, Medical technology, R855-855.5
Abstract: Background Arteriovenous fistulas are considered the best option for haemodialysis provision, but as many as 30% fail to mature or suffer early failure. Objective To assess the feasibility of performing a randomised controlled trial that examines whether, by informing early and effective salvage intervention of fistulas that would otherwise fail, Doppler ultrasound surveillance of developing arteriovenous fistulas improves longer-term arteriovenous fistula patency. Design A prospective multicentre observational cohort study (the ‘SONAR’ study). Setting Seventeen haemodialysis centres in the UK. Participants Consenting adults with end-stage renal disease who were scheduled to have an arteriovenous fistula created. Intervention Participants underwent Doppler ultrasound surveillance of their arteriovenous fistulas at 2, 4, 6 and 10 weeks after creation, with clinical teams blinded to the ultrasound surveillance findings. Main outcome measures Fistula maturation at week 10 defined according to ultrasound surveillance parameters of representative venous diameter and blood flow (wrist arteriovenous fistulas: ≥ 4 mm and > 400 ml/minute; elbow arteriovenous fistulas: ≥ 5 mm and > 500 ml/minute). Mixed multivariable logistic regression modelling of the early ultrasound scan data was used to predict arteriovenous fistula non-maturation by 10 weeks and fistula failure at 6 months. Results A total of 333 arteriovenous fistulas were created during the study window (47.7% wrist, 52.3% elbow). By 2 weeks, 37 (11.1%) arteriovenous fistulas had failed (thrombosed), but by 10 weeks, 219 of 333 (65.8%) of created arteriovenous fistulas had reached maturity (60.4% wrist, 67.2% elbow). Persistently lower flow rates and venous diameters were observed in those fistulas that did not mature. Models for arteriovenous fistulas’ non-maturation could be optimally constructed using the week 4 scan data, with fistula venous diameter and flow rate the most significant variables in explaining wrist fistula maturity failure (positive predictive value 60.6%, 95% confidence interval 43.9% to 77.3%), whereas resistance index and flow rate were most significant for elbow arteriovenous fistulas (positive predictive value 66.7%, 95% confidence interval 48.9% to 84.4%). In contrast to non-maturation, both models predicted fistula maturation much more reliably [negative predictive values of 95.4% (95% confidence interval 91.0% to 99.8%) and 95.6% (95% confidence interval 91.8% to 99.4%) for wrist and elbow, respectively]. Additional follow-up and modelling on a subset (n = 192) of the original SONAR cohort (the SONAR-12M study) revealed the rates of primary, assisted primary and secondary patency arteriovenous fistulas at 6 months were 76.5, 80.7 and 83.3, respectively. Fistula vein size, flow rate and resistance index could identify primary patency failure at 6 months, with similar predictive power as for 10-week arteriovenous fistula maturity failure, but with wide confidence intervals for wrist (positive predictive value 72.7%, 95% confidence interval 46.4% to 99.0%) and elbow (positive predictive value 57.1%, 95% confidence interval 20.5% to 93.8%). These models, moreover, performed poorly at identifying assisted primary and secondary patency failure, likely because a subset of those arteriovenous fistulas identified on ultrasound surveillance as at risk underwent subsequent successful salvage intervention without recourse to early ultrasound data. Conclusions Although early ultrasound can predict fistula maturation and longer-term patency very effectively, it was only moderately good at identifying those fistulas likely to remain immature or to fail within 6 months. Allied to the better- than-expected fistula patency rates achieved (that are further improved by successful salvage), we estimate that a randomised controlled trial comparing early ultrasound-guided intervention against standard care would require at least 1300 fistulas and would achieve only minimal patient benefit. Trial Registration This trial is registered as ISRCTN36033877 and ISRCTN17399438. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135572) and is published in full in Health Technology Assessment; Vol. 28, No. 24. See the NIHR Funding and Awards website for further award information. Plain language summary What was the problem? For people with advanced kidney disease, haemodialysis is best provided by an ‘arteriovenous fistula’, which is created surgically by joining a vein onto an artery at the wrist or elbow. However, these take about 2 months to develop fully (‘mature’), and as many as 3 out of 10 fail to do so. What was the question? We asked whether we could use early ultrasound scanning of the fistula to identify those that are unlikely to mature. This would allow us to decide whether it would be practical to run a large, randomised trial to find out if using early ultrasound allows us to ‘rescue’ fistulas that would otherwise fail. What did we do? We invited adults to undergo serial ultrasound scanning of their fistula in the first few weeks after it was created. We then analysed whether we could use the data from the early scans to identify those fistulas that were not going to mature by week 10. What did we find? Of the 333 fistulas that were created, about two-thirds reached maturity by week 10. We found that an ultrasound scan 4 weeks after fistula creation could reliably identify those fistulas that were going to mature. However, of those fistulas predicted to fail, about one-third did eventually mature without further intervention, and even without knowing what the early scans showed, another third were successfully rescued by surgery or X-ray-guided treatment at a later stage. What does this mean? Performing an early ultrasound scan on a fistula can provide reassurance that it will mature and deliver trouble-free dialysis. However, because scans are poor at identifying fistulas that are unlikely to mature, we would not recommend their use to justify early surgery or X-ray-guided treatment in the expectation that this will improve outcomes. Scientific summary Background Because of their favourable durability and low infection rates, arteriovenous fistulas (AVFs) are considered the best option for provision of haemodialysis, and they offer survival advantages compared to dialysis through a central venous catheter (CVC). Upon surgical creation, AVFs undergo a period of ‘maturation’, wherein the transit of high-pressure arterial flow through the anastomosis triggers compensatory dilatation and thickening of the draining fistula vein, with marked increases in blood flow through the AVF. This maturation, which generally takes about 2 months, is required to achieve functionality and enables the AVF to be used for dialysis. The main drawback with AVFs is that a large proportion (in excess of 30% in some series) do not develop fully, and either thrombose or remain patent in an immature state. This necessitates further surgical or radiological interventions to aid maturation, or formation of an entirely new fistula, thus potentially prolonging the requirement for dialysis through a CVC. Strategies to increase maturation rates and early patency of AVFs may therefore make a substantial difference to patient outcomes. In this respect, widespread patient and clinician consultation, supported by the James Lind Alliance, has identified the question, ‘What can be done to make fistulas or grafts last as long as possible?’ as one of the top 10 research priorities in vascular access provision. One possible approach to counter early fistula loss from non-maturation/thrombosis is to use Doppler ultrasound (US) surveillance in the first few weeks after creation to identify at-risk fistulas and to inform early radiological or surgical intervention, in anticipation that this improves longer-term fistula patency. This has, however, not yet been tested. The SONAR consortium, representing 17 UK centres that provide vascular access surgery, was established to test the hypothesis: Doppler US surveillance of AVFs immediately after creation improves longer-term AVF patency, by directing early and effective surgical or radiological salvage of those AVFs at risk of failing or not maturing. Objectives In considering the above hypothesis, several conditions must be met if US-guided early salvage intervention is to improve outcomes following AVF creation: that US can effectively distinguish those newly formed fistulas that are unlikely to mature that maturity failure occurs commonly enough that clinically meaningful improvements in fistula outcomes by early identification of at-risk fistulas are plausible that salvage interventions performed on those ‘at-risk’ fistulas are effective and improve fistula patency. The SONAR study thus aimed to address the following objectives sequentially, over a 5-year window: Run an observational cohort study in which consenting participants undergo serial US assessment of their AVF in the first 3 months after its formation (phase 1). Model whether features on early US can reliably identify those fistulas that will not mature or will fail early. Assess from the observational cohort study whether a randomised controlled trial (RCT) evaluating early US-guided salvage intervention is feasible. Run a multicentre RCT in which 1-year fistula patency in a treatment group receiving early US surveillance of their developing fistula is compared against standard care: monitoring of fistula maturation by clinical assessment only (phase 2). Progression to the phase 2 study depended upon accomplishing the first three objectives and, in particular, demonstrating that US surveillance could accurately predict fistula non-maturation. This manuscript will thus focus on the phase 1 study set-up and outcomes. Methods A prospective multicentre observational cohort study of adult patients undergoing formation of AVF for haemodialysis was performed to test the hypothesis: Doppler US surveillance early after AVF creation can reliably identify those AVFs that will not mature or will fail early. Criteria for participation were as follows: Adult, aged 16 years or older. The participant had end-stage renal disease and was either already established on haemodialysis or likely to start imminently. The participant was due creation of an arm AVF (either wrist or elbow) including the following types of fistula: radiocephalic, ulnobasilic, brachiocephalic and brachiobasilic (one- or two-stage) fistula, with a minimal acceptable threshold of 2 mm venous diameter at whatever site was chosen. Full informed consent to participate was provided. Consenting participants underwent serial US scanning at weeks 2, 4, 6 and 10 after fistula formation in addition to standard care (such as regular clinical assessment) as per local centre policy. Fistula flow rates, fistula venous diameter and resistance index were recorded, according to a standard study protocol, with clinical teams blinded to the US findings, unless a scan was simultaneously requested on clinical grounds or the scan confirmed thrombosis of the fistula. The primary outcome measure was fistula maturation at 10 weeks. To encompass participants who remained pre-dialysis, along with clinical examination, maturation was assessed at 10 weeks according to accepted surrogate US parameters: wrist fistula: representative venous diameter ≥ 4 mm, with flow > 400 ml/minute elbow fistula: representative venous fistula diameter ≥ 5 mm, with flow > 500 ml/minute. Three distinct outcomes defined fistula non-maturation: a fistula occlusion/thrombosis within the study period (76 days post AVF creation) fistula abandonment within the study period due to failure to mature or due to thrombosis/occlusion failure to achieve (either reported at the week 10 scan or imputed) maturation, according to the preset US parameters. The following secondary outcome measures were also recorded: for those patients established on dialysis, successful use of the fistula for dialysis on three successive occasions clinical suitability for dialysis 10 weeks after fistula creation based on examination alone according to local practice formation of a new fistula (including fashioning of proximal neoanastomosis) or radiological salvage procedure fistula thrombosis secondary fistula patency patient acceptability, based on the proportion of patients that complete their scans. Assuming that early US surveillance predicts fistula non-maturation/failure in 25% of AVFs, a total of 347 fistulas were required to achieve precision of ± 10% for an estimated 72% positive predictive value (PPV) for detecting non-maturation/failure. The total sample size allows for 10% dropout. Mixed multivariable logistic regression (binary-data population-average model with exchangeable correlation structure) of the early US scan data was then used to build separate models for wrist and elbow AVF that contained the minimum number of measurements required to predict AVF non-maturation by 10 weeks. Receiver operating characteristic curves of the developed risk scores were analysed to determine when surgical or radiological intervention on the developing AVF could be considered. The PPV and negative predictive value (NPV; the probability of AVF maturation given that the model predicts maturation) were calculated alongside a 95% confidence interval (CI) for the chosen risk-score cut-off. Additional modelling was then performed on a subset (n = 192) of the original SONAR cohort available for follow-up, to assess whether fistula failure at 6 and 12 months could be identified by analysis of early US characteristics. The primary outcome measure for the longer-term follow-up was primary fistula patency at 6 months, defined as ‘the interval between access creation to the earliest time of fistula thrombosis, abandonment (except abandonment because of steal), intervention on the fistula (to re-establish or maintain patency) or the time of measurement of patency’. Secondary outcome measures included assisted primary patency (the interval from access creation until access thrombosis or the time of measurement of patency, including any interventions to maintain patency) and secondary patency (the interval from access creation to time of measurement of patency or to abandonment of the fistula). Similar binary-data population-average modelling was performed as for predicting 10-week non-maturation, aiming to build parsimonious models that contained the minimum number of variables from one scan time point (at either week 4 or week 6) to effectively predict primary fistula non-patency at 6 months. Results Of 347 consents to participation (median age 65 years; interquartile range 52–74 years; 64.8% male; 43.2% diabetic; 55.0% pre-dialysis), 333 underwent AVF creation during the study window (47.7% wrist, 52.3% elbow fistula). Early failure before the first US scan occurred in 37 (11.1%) AVFs, but by 10 weeks, 219 of 333 (65.8%) created AVFs had reached maturity (67.2% elbow, 60.4% wrist). Of the remainder, by week 10 a further 20 had failed (57 failures in total; 17.1%), 29 (8.7%) remained patent but not mature and the status of 28 (8.4%) was unknown. Excluding those failures occurring within the first 2 weeks (because it would be impractical to organise salvage so quickly) results in a fistula maturation rate of 74.0% at 10 weeks. Serial US scanning revealed that maturation occurred rapidly (the vast majority of AVFs that were mature by 10 weeks had reached maturation by 2 weeks). Comparison of the early scan data in those AVFs that had matured by week 10 against those AVFs that remained immature (see Figure 4) revealed consistently lower fistula flow rates and fistula vein diameter in the latter. For example, the median blood flow at 2 weeks was 1135.5 and 691.0 ml/minute in those elbow and wrist fistulas, respectively, that reached maturation by week 10, whereas week 2 flows of 349.0 and 395.5 ml/minute were recorded in those elbow and wrist fistulas that did not reach maturation at week 10. Modelling to predict AVF non-maturation at week 10 was optimally built on the week 4 scan data but required separate algorithms for wrist and elbow fistulas, with fistula venous diameter and flow rate at week 4 identified as the most significant variables in explaining wrist fistula maturity failure (PPV 60.6%, 95% CI 43.9% to 77.3%), whereas resistance index and flow rate were most significant for elbow fistula maturity failure (PPV 66.7%, 95% CI 48.9% to 84.4%). Diagnostic tests for model fit and influential observations were run on the optimum models for wrist and elbow AVFs, with both performing well, with area under the curve values of at least 0.90. Conversely, both models could predict fistula maturation much more reliably [NPVs of 95.4% (91.0–99.8) and 95.6% (91.8–99.4) for wrist and elbow, respectively]. Additional modelling was then performed on a subset (n = 192) of the original SONAR cohort available for follow-up, to assess whether fistula failure at 6 and 12 months could be identified by analysis of early US characteristics. Primary, assisted primary and secondary patency AVF rates at 6 months were 76.5%, 80.7% and 83.3%, respectively, and at 12 months were 68.3%, 74.1% and 79.5%, respectively. Broadly similar US characteristics (fistula vein size, flow rate and resistance index) were identified as the most significant variables predicting primary patency failure at 6 months, with similar predictive power as for 10-week AVF maturity failure, but with wide CIs (wrist AVF: PPV 72.7%, 95% CI 46.4% to 99.0%; elbow AVF: 57.1%, 95% CI 20.5% to 93.8%). Moreover, the models performed very poorly at identifying assisted primary and secondary patency failure, likely because a subset of those identified as liable to fail were instead successfully salvaged by radiological or surgical intervention. Conclusions Although early US can predict fistula maturation and longer-term patency very effectively, it was only moderately good at identifying those unlikely to mature or to fail within 6 months. Allied to the better than expected fistula patency rate achieved by the SONAR consortium (that is further improved by successful radiological or survival salvage without recourse to the early US data), we estimate that a prospective randomised trial comparing early US-guided intervention against standard care (observation only) would require at least 1300 fistulas and would only achieve a minimally clinically important difference in the intervention arm if virtually every intervention were successful in maintaining/restoring fistula patency. Limitations The US scan findings were generally not made available to the clinical teams, so as to avoid their influencing participant management. However, scan results were revealed to the responsible clinical team on 98 occasions (10.7% of all scans), either because an early US scan was standard care for that unit (76 occasions) or because unblinding was requested because of clinical concern relating to the fistula’s maturation. It is therefore possible that in a small number of cases, the study US scans triggered salvage procedures that would not otherwise have been performed on clinical grounds alone. This is particularly problematic for the 12-month follow-up study, because the intervention would mark the end of primary patency – the primary outcome measure for the 6-month analysis – and it would therefore provide false support for the statistical modelling. However, in the majority of cases, unblinding did not prompt further intervention (simply instead confirming fistula maturation), and thus is unlikely to have compromised the statistical modelling. Similarly, to include pre-dialysis patients in the study, it was necessary to adopt surrogate US markers to define fistula maturation, and it is perhaps not ideal to be using the same modality to delineate the maturation process as one uses to define maturation, particularly because fistula maturation is principally a functional concern relating to whether the fistula can be used to provide adequate dialysis. Repeat US was not performed at 6 months for the follow-up study, and the analysis of fistula patency, rather than maturation status, provides a better reflection of fistula functionality. This may partly explain the differences in the modelling findings between the 10-week and 6-month studies. Trial registration The SONAR study was approved by the Cambridgeshire and Hertfordshire Research Ethics Committee and by the Health Research Authority (REC 18/EE/0234) and assigned ISRCTN36033877. The SONAR-12M study was approved by the West Midlands – Edgbaston Research Ethics Committee (REC 20/WM/0331) and assigned ISRCTN17399438. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135572) and is published in full in Health Technology Assessment; Vol. 28, No. 24. See the NIHR Funding and Awards website for further award information.
Published: 2024
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3. The SWiFT trial (Study of Whole Blood in Frontline Trauma)—the clinical and cost effectiveness of pre-hospital whole blood versus standard care in patients with life-threatening traumatic haemorrhage: study protocol for a multi-centre randomised controlled trial

Author: Jason E. Smith, Ed B. G. Barnard, Charlie Brown-O’Sullivan, Rebecca Cardigan, Jane Davies, Annie Hawton, Emma Laing, Joanne Lucas, Richard Lyon, Gavin D. Perkins, Laura Smith, Simon J. Stanworth, Anne Weaver, Tom Woolley, and Laura Green
Subjects: Emergency medicine, Major trauma, Major haemorrhage, Transfusion, Pre-hospital, Whole blood, Medicine (General), R5-920
Abstract: Abstract Background Early blood transfusion improves survival in patients with life-threatening bleeding, but the optimal transfusion strategy in the pre-hospital setting has yet to be established. Although there is some evidence of benefit with the use of whole blood, there have been no randomised controlled trials exploring the clinical and cost effectiveness of pre-hospital administration of whole blood versus component therapy for trauma patients with life-threatening bleeding. The aim of this trial is to determine whether pre-hospital leukocyte-depleted whole blood transfusion is better than standard care (blood component transfusion) in reducing the proportion of participants who experience death or massive transfusion at 24 h. Methods This is a multi-centre, superiority, open-label, randomised controlled trial with internal pilot and within-trial cost-effectiveness analysis. Patients of any age will be eligible if they have suffered major traumatic haemorrhage and are attended by a participating air ambulance service. The primary outcome is the proportion of participants with traumatic haemorrhage who have died (all-cause mortality) or received massive transfusion in the first 24 h from randomisation. A number of secondary clinical, process, and safety endpoints will be collected and analysed. Cost (provision of whole blood, hospital, health, and wider care resource use) and outcome data will be synthesised to present incremental cost-effectiveness ratios for the trial primary outcome and cost per quality-adjusted life year at 90 days after injury. We plan to recruit 848 participants (a two-sided test with 85% power, 5% type I error, 1-1 allocation, and one interim analysis would require 602 participants—after allowing for 25% of participants in traumatic cardiac arrest and an additional 5% drop out, the sample size is 848). Discussion The SWiFT trial will recruit 848 participants across at least ten air ambulances services in the UK. It will investigate the clinical and cost-effectiveness of whole blood transfusion versus component therapy in the management of patients with life-threatening bleeding in the pre-hospital setting. Trial registration ISRCTN: 23657907; EudraCT: 2021-006876-18; IRAS Number: 300414; REC: 22/SC/0072, 21 Dec 2021.
Published: 2023
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4. Benchmarking causal reasoning algorithms for gene expression-based compound mechanism of action analysis

Author: Layla Hosseini-Gerami, Ixavier Alonzo Higgins, David A. Collier, Emma Laing, David Evans, Howard Broughton, and Andreas Bender
Subjects: Transcriptomics, Causal reasoning, Mechanism of action, Network Biology, Benchmarking, L1000, Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract: Abstract Background Elucidating compound mechanism of action (MoA) is beneficial to drug discovery, but in practice often represents a significant challenge. Causal Reasoning approaches aim to address this situation by inferring dysregulated signalling proteins using transcriptomics data and biological networks; however, a comprehensive benchmarking of such approaches has not yet been reported. Here we benchmarked four causal reasoning algorithms (SigNet, CausalR, CausalR ScanR and CARNIVAL) with four networks (the smaller Omnipath network vs. 3 larger MetaBase™ networks), using LINCS L1000 and CMap microarray data, and assessed to what extent each factor dictated the successful recovery of direct targets and compound-associated signalling pathways in a benchmark dataset comprising 269 compounds. We additionally examined impact on performance in terms of the functions and roles of protein targets and their connectivity bias in the prior knowledge networks. Results According to statistical analysis (negative binomial model), the combination of algorithm and network most significantly dictated the performance of causal reasoning algorithms, with the SigNet recovering the greatest number of direct targets. With respect to the recovery of signalling pathways, CARNIVAL with the Omnipath network was able to recover the most informative pathways containing compound targets, based on the Reactome pathway hierarchy. Additionally, CARNIVAL, SigNet and CausalR ScanR all outperformed baseline gene expression pathway enrichment results. We found no significant difference in performance between L1000 data or microarray data, even when limited to just 978 ‘landmark’ genes. Notably, all causal reasoning algorithms also outperformed pathway recovery based on input DEGs, despite these often being used for pathway enrichment. Causal reasoning methods performance was somewhat correlated with connectivity and biological role of the targets. Conclusions Overall, we conclude that causal reasoning performs well at recovering signalling proteins related to compound MoA upstream from gene expression changes by leveraging prior knowledge networks, and that the choice of network and algorithm has a profound impact on the performance of causal reasoning algorithms. Based on the analyses presented here this is true for both microarray-based gene expression data as well as those based on the L1000 platform.
Published: 2023
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5. Mechanism of action deconvolution of the small-molecule pathological tau aggregation inhibitor Anle138b

Author: Layla Hosseini-Gerami, Elena Ficulle, Neil Humphryes-Kirilov, David C. Airey, James Scherschel, Sarubini Kananathan, Brian J. Eastwood, Suchira Bose, David A. Collier, Emma Laing, David Evans, Howard Broughton, and Andreas Bender
Subjects: Transcriptomics, Bioinformatics, Machine learning, Network biology, Tau, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background A key histopathological hallmark of Alzheimer’s disease (AD) is the presence of neurofibrillary tangles of aggregated microtubule-associated protein tau in neurons. Anle138b is a small molecule which has previously shown efficacy in mice in reducing tau aggregates and rescuing AD disease phenotypes. Methods In this work, we employed bioinformatics analysis—including pathway enrichment and causal reasoning—of an in vitro tauopathy model. The model consisted of cultured rat cortical neurons either unseeded or seeded with tau aggregates derived from human AD patients, both of which were treated with Anle138b to generate hypotheses for its mode of action. In parallel, we used a collection of human target prediction models to predict direct targets of Anle138b based on its chemical structure. Results Combining the different approaches, we found evidence supporting the hypothesis that the action of Anle138b involves several processes which are key to AD progression, including cholesterol homeostasis and neuroinflammation. On the pathway level, we found significantly enriched pathways related to these two processes including those entitled “Superpathway of cholesterol biosynthesis” and “Granulocyte adhesion and diapedesis”. With causal reasoning, we inferred differential activity of SREBF1/2 (involved in cholesterol regulation) and mediators of the inflammatory response such as NFKB1 and RELA. Notably, our findings were also observed in Anle138b-treated unseeded neurons, meaning that the inferred processes are independent of tau pathology and thus represent the direct action of the compound in the cellular system. Through structure-based ligand-target prediction, we predicted the intracellular cholesterol carrier NPC1 as well as NF-κB subunits as potential targets of Anle138b, with structurally similar compounds in the model training set known to target the same proteins. Conclusions This study has generated feasible hypotheses for the potential mechanism of action of Anle138b, which will enable the development of future molecular interventions aiming to reduce tau pathology in AD patients.
Published: 2023
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6. A human tau seeded neuronal cell model recapitulates molecular responses associated with Alzheimer’s disease

Author: Elena Ficulle, Sarubini Kananathan, David Airey, Severine I. Gharbi, Neil Humphryes-Kirilov, James Scherschel, Charlotte Dunbar, Brian J. Eastwood, Emma Laing, David A. Collier, and Suchira Bose
Subjects: Medicine, Science
Abstract: Abstract Cellular models recapitulating features of tauopathies are useful tools to investigate the causes and consequences of tau aggregation and the identification of novel treatments. We seeded rat primary cortical neurons with tau isolated from Alzheimer’s disease brains to induce a time-dependent increase in endogenous tau inclusions. Transcriptomics of seeded and control cells identified 1075 differentially expressed genes (including 26 altered at two time points). These were enriched for lipid/steroid metabolism and neuronal/glial cell development genes. 50 genes were correlated with tau inclusion formation at both transcriptomic and proteomic levels, including several microtubule and cytoskeleton-related proteins such as Tubb2a, Tubb4a, Nefl and Snca. Several genes (such as Fyn kinase and PTBP1, a tau exon 10 repressor) interact directly with or regulate tau. We conclude that this neuronal model may be a suitable platform for high-throughput screens for target or hit compound identification and validation.
Published: 2022
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7. Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author: Cathrine Axfors, Perrine Janiaud, Andreas M. Schmitt, Janneke van’t Hooft, Emily R. Smith, Noah A. Haber, Akin Abayomi, Manal Abduljalil, Abdulkarim Abdulrahman, Yeny Acosta-Ampudia, Manuela Aguilar-Guisado, Farah Al-Beidh, Marissa M. Alejandria, Rachelle N. Alfonso, Mohammad Ali, Manaf AlQahtani, Alaa AlZamrooni, Juan-Manuel Anaya, Mark Angelo C. Ang, Ismael F. Aomar, Luis E. Argumanis, Alexander Averyanov, Vladimir P. Baklaushev, Olga Balionis, Thomas Benfield, Scott Berry, Nadia Birocco, Lynn B. Bonifacio, Asha C. Bowen, Abbie Bown, Carlos Cabello-Gutierrez, Bernardo Camacho, Adrian Camacho-Ortiz, Sally Campbell-Lee, Damon H. Cao, Ana Cardesa, Jose M. Carnate, German Jr. J. Castillo, Rossana Cavallo, Fazle R. Chowdhury, Forhad U. H. Chowdhury, Giovannino Ciccone, Antonella Cingolani, Fresthel Monica M. Climacosa, Veerle Compernolle, Carlo Francisco N. Cortez, Abel Costa Neto, Sergio D’Antico, James Daly, Franca Danielle, Joshua S. Davis, Francesco Giuseppe De Rosa, Justin T. Denholm, Claudia M. Denkinger, Daniel Desmecht, Juan C. Díaz-Coronado, Juan A. Díaz Ponce-Medrano, Anne-Françoise Donneau, Teresita E. Dumagay, Susanna Dunachie, Cecile C. Dungog, Olufemi Erinoso, Ivy Mae S. Escasa, Lise J. Estcourt, Amy Evans, Agnes L. M. Evasan, Christian J. Fareli, Veronica Fernandez-Sanchez, Claudia Galassi, Juan E. Gallo, Patricia J. Garcia, Patricia L. Garcia, Jesus A. Garcia, Mutien Garigliany, Elvira Garza-Gonzalez, Deonne Thaddeus V. Gauiran, Paula A. Gaviria García, Jose-Antonio Giron-Gonzalez, David Gómez-Almaguer, Anthony C. Gordon, André Gothot, Jeser Santiago Grass Guaqueta, Cameron Green, David Grimaldi, Naomi E. Hammond, Heli Harvala, Francisco M. Heralde, Jesica Herrick, Alisa M. Higgins, Thomas E. Hills, Jennifer Hines, Karin Holm, Ashraful Hoque, Eric Hoste, Jose M. Ignacio, Alexander V. Ivanov, Maike Janssen, Jeffrey H. Jennings, Vivekanand Jha, Ruby Anne N. King, Jens Kjeldsen-Kragh, Paul Klenerman, Aditya Kotecha, Fiorella Krapp, Luciana Labanca, Emma Laing, Mona Landin-Olsson, Pierre-François Laterre, Lyn-Li Lim, Jodor Lim, Oskar Ljungquist, Jorge M. Llaca-Díaz, Concepción López-Robles, Salvador López-Cárdenas, Ileana Lopez-Plaza, Josephine Anne C. Lucero, Maria Lundgren, Juan Macías, Sandy C. Maganito, Anna Flor G. Malundo, Rubén D. Manrique, Paola M. Manzini, Miguel Marcos, Ignacio Marquez, Francisco Javier Martínez-Marcos, Ana M. Mata, Colin J. McArthur, Zoe K. McQuilten, Bryan J. McVerry, David K. Menon, Geert Meyfroidt, Ma. Angelina L. Mirasol, Benoît Misset, James S. Molton, Alric V. Mondragon, Diana M. Monsalve, Parastoo Moradi Choghakabodi, Susan C. Morpeth, Paul R. Mouncey, Michel Moutschen, Carsten Müller-Tidow, Erin Murphy, Tome Najdovski, Alistair D. Nichol, Henrik Nielsen, Richard M. Novak, Matthew V. N. O’Sullivan, Julian Olalla, Akin Osibogun, Bodunrin Osikomaiya, Salvador Oyonarte, Juan M. Pardo-Oviedo, Mahesh C. Patel, David L. Paterson, Carlos A. Peña-Perez, Angel A. Perez-Calatayud, Eduardo Pérez-Alba, Anastasia Perkina, Naomi Perry, Mandana Pouladzadeh, Inmaculada Poyato, David J. Price, Anne Kristine H. Quero, Md. M. Rahman, Md. S. Rahman, Mayur Ramesh, Carolina Ramírez-Santana, Magnus Rasmussen, Megan A. Rees, Eduardo Rego, Jason A. Roberts, David J. Roberts, Yhojan Rodríguez, Jesús Rodríguez-Baño, Benjamin A. Rogers, Manuel Rojas, Alberto Romero, Kathryn M. Rowan, Fabio Saccona, Mehdi Safdarian, Maria Clariza M. Santos, Joe Sasadeusz, Gitana Scozzari, Manu Shankar-Hari, Gorav Sharma, Thomas Snelling, Alonso Soto, Pedrito Y. Tagayuna, Amy Tang, Geneva Tatem, Luciana Teofili, Steven Y. C. Tong, Alexis F. Turgeon, Januario D. Veloso, Balasubramanian Venkatesh, Yanet Ventura-Enriquez, Steve A. Webb, Lothar Wiese, Christian Wikén, Erica M. Wood, Gaukhar M. Yusubalieva, Kai Zacharowski, Ryan Zarychanski, Nina Khanna, David Moher, Steven N. Goodman, John P. A. Ioannidis, and Lars G. Hemkens
Subjects: Meta-analysis, SARS-CoV-2, COVID-19, Convalescent plasma, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). Methods In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
Published: 2021
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8. An inter-laboratory study to investigate the impact of the bioinformatics component on microbiome analysis using mock communities

Author: Denise M. O’Sullivan, Ronan M. Doyle, Sasithon Temisak, Nicholas Redshaw, Alexandra S. Whale, Grace Logan, Jiabin Huang, Nicole Fischer, Gregory C. A. Amos, Mark D. Preston, Julian R. Marchesi, Josef Wagner, Julian Parkhill, Yair Motro, Hubert Denise, Robert D. Finn, Kathryn A. Harris, Gemma L. Kay, Justin O’Grady, Emma Ransom-Jones, Huihai Wu, Emma Laing, David J. Studholme, Ernest Diez Benavente, Jody Phelan, Taane G. Clark, Jacob Moran-Gilad, and Jim F. Huggett
Subjects: Medicine, Science
Abstract: Abstract Despite the advent of whole genome metagenomics, targeted approaches (such as 16S rRNA gene amplicon sequencing) continue to be valuable for determining the microbial composition of samples. Amplicon microbiome sequencing can be performed on clinical samples from a normally sterile site to determine the aetiology of an infection (usually single pathogen identification) or samples from more complex niches such as human mucosa or environmental samples where multiple microorganisms need to be identified. The methodologies are frequently applied to determine both presence of micro-organisms and their quantity or relative abundance. There are a number of technical steps required to perform microbial community profiling, many of which may have appreciable precision and bias that impacts final results. In order for these methods to be applied with the greatest accuracy, comparative studies across different laboratories are warranted. In this study we explored the impact of the bioinformatic approaches taken in different laboratories on microbiome assessment using 16S rRNA gene amplicon sequencing results. Data were generated from two mock microbial community samples which were amplified using primer sets spanning five different variable regions of 16S rRNA genes. The PCR-sequencing analysis included three technical repeats of the process to determine the repeatability of their methods. Thirteen laboratories participated in the study, and each analysed the same FASTQ files using their choice of pipeline. This study captured the methods used and the resulting sequence annotation and relative abundance output from bioinformatic analyses. Results were compared to digital PCR assessment of the absolute abundance of each target representing each organism in the mock microbial community samples and also to analyses of shotgun metagenome sequence data. This ring trial demonstrates that the choice of bioinformatic analysis pipeline alone can result in different estimations of the composition of the microbiome when using 16S rRNA gene amplicon sequencing data. The study observed differences in terms of both presence and abundance of organisms and provides a resource for ensuring reproducible pipeline development and application. The observed differences were especially prevalent when using custom databases and applying high stringency operational taxonomic unit (OTU) cut-off limits. In order to apply sequencing approaches with greater accuracy, the impact of different analytical steps needs to be clearly delineated and solutions devised to harmonise microbiome analysis results.
Published: 2021
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9. Multicentre randomised controlled trial: protocol for Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO)

Author: Mark J Peters, Laura Pankhurst, Emma Laing, Jo Wray, Claire Foley, Helen Thomas, Wesley Hayes, Stephen Marks, Nicos Kessaris, Anastassia Spiridou, William A Bryant, and Helen Hume-Smith
Subjects: Medicine
Abstract: Introduction Acute electrolyte and acid–base imbalance is experienced by many children following kidney transplantation. When severe, this can lead to complications including seizures, cerebral oedema and death. Relatively large volumes of intravenous fluid are administered to children perioperatively in order to establish perfusion to the donor kidney, the majority of which are from living and deceased adult donors. Hypotonic intravenous fluid is commonly used in the post-transplant period due to clinicians’ concerns about the sodium, chloride and potassium content of isotonic alternatives when administered in large volumes.Plasma-Lyte 148 is an isotonic, balanced intravenous fluid that contains sodium, chloride, potassium and magnesium with concentrations equivalent to those of plasma. There is a physiological basis to expect that Plasma-Lyte 148 will reduce the incidence of clinically significant electrolyte and acid–base abnormalities in children following kidney transplantation compared with current practice.The aim of the PLUTO trial is to determine whether the incidence of clinically significantly abnormal plasma electrolyte levels in paediatric kidney transplant recipients will be different with the use of Plasma-Lyte-148 compared to intravenous fluid currently administered.Methods and analysis PLUTO is a pragmatic, open-label, randomised controlled trial comparing Plasma-Lyte 148 to current care in paediatric kidney transplant recipients, conducted in nine UK paediatric kidney transplant centres.A total of 144 children receiving kidney transplants will be randomised to receive either Plasma-Lyte 148 (the intervention) intraoperatively and postoperatively, or current fluid. Apart from intravenous fluid composition, all participants will receive standard clinical transplant care.The primary outcome measure is acute hyponatraemia in the first 72 hours post-transplant, defined as laboratory plasma sodium concentration of
Published: 2022
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10. Correction: King et al. Establishing an In Vitro System to Assess How Specific Antibodies Drive the Evolution of Foot-and-Mouth Disease Virus. Viruses 2022, 14, 1820

Author: David J. King, Graham Freimanis, Chris Neil, Andrew Shaw, Tobias J. Tuthill, Emma Laing, Donald P. King, and Lidia Lasecka-Dykes
Subjects: n/a, Microbiology, QR1-502
Abstract: In the original publication [...]
Published: 2023
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11. Establishing an In Vitro System to Assess How Specific Antibodies Drive the Evolution of Foot-and-Mouth Disease Virus

Author: David J. King, Graham Freimanis, Chris Neil, Andrew Shaw, Tobias J. Tuthill, Emma Laing, Donald P. King, and Lidia Lasecka-Dykes
Subjects: immune escape, foot-and-mouth disease virus, in vitro, virus evolution, Microbiology, QR1-502
Abstract: Viruses can evolve to respond to immune pressures conferred by specific antibodies generated after vaccination and/or infection. In this study, an in vitro system was developed to investigate the impact of serum-neutralising antibodies upon the evolution of a foot-and-mouth disease virus (FMDV) isolate. The presence of sub-neutralising dilutions of specific antisera delayed the onset of virus-induced cytopathic effect (CPE) by up to 44 h compared to the untreated control cultures. Continued virus passage with sub-neutralising dilutions of these sera resulted in a decrease in time to complete CPE, suggesting that FMDV in these cultures adapted to escape immune pressure. These phenotypic changes were associated with three separate consensus-level non-synonymous mutations that accrued in the viral RNA-encoding amino acids at positions VP266, VP280 and VP1155, corresponding to known epitope sites. High-throughput sequencing also identified further nucleotide substitutions within the regions encoding the leader (Lpro), VP4, VP2 and VP3 proteins. While association of the later mutations with the adaptation to immune pressure must be further verified, these results highlight the multiple routes by which FMDV populations can escape neutralising antibodies and support the application of a simple in vitro approach to assess the impact of the humoral immune system on the evolution of FMDV and potentially other viruses.
Published: 2022
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12. A systematic evaluation of Mycobacterium tuberculosis Genome-Scale Metabolic Networks.

Author: Víctor A López-Agudelo, Tom A Mendum, Emma Laing, HuiHai Wu, Andres Baena, Luis F Barrera, Dany J V Beste, and Rigoberto Rios-Estepa
Subjects: Biology (General), QH301-705.5
Abstract: Metabolism underpins the pathogenic strategy of the causative agent of TB, Mycobacterium tuberculosis (Mtb), and therefore metabolic pathways have recently re-emerged as attractive drug targets. A powerful approach to study Mtb metabolism as a whole, rather than just individual enzymatic components, is to use a systems biology framework, such as a Genome-Scale Metabolic Network (GSMN) that allows the dynamic interactions of all the components of metabolism to be interrogated together. Several GSMNs networks have been constructed for Mtb and used to study the complex relationship between the Mtb genotype and its phenotype. However, the utility of this approach is hampered by the existence of multiple models, each with varying properties and performances. Here we systematically evaluate eight recently published metabolic models of Mtb-H37Rv to facilitate model choice. The best performing models, sMtb2018 and iEK1011, were refined and improved for use in future studies by the TB research community.
Published: 2020
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13. Transcriptional Signatures of Tau and Amyloid Neuropathology

Author: Isabel Castanho, Tracey K. Murray, Eilis Hannon, Aaron Jeffries, Emma Walker, Emma Laing, Hedley Baulf, Joshua Harvey, Lauren Bradshaw, Andrew Randall, Karen Moore, Paul O’Neill, Katie Lunnon, David A. Collier, Zeshan Ahmed, Michael J. O’Neill, and Jonathan Mill
Subjects: Biology (General), QH301-705.5
Abstract: Summary: Alzheimer’s disease (AD) is associated with the intracellular aggregation of hyperphosphorylated tau and the accumulation of β-amyloid in the neocortex. We use transgenic mice harboring human tau (rTg4510) and amyloid precursor protein (J20) mutations to investigate transcriptional changes associated with the progression of tau and amyloid pathology. rTg4510 mice are characterized by widespread transcriptional differences in the entorhinal cortex with changes paralleling neuropathological burden across multiple brain regions. Differentially expressed transcripts overlap with genes identified in genetic studies of familial and sporadic AD. Systems-level analyses identify discrete co-expression networks associated with the progressive accumulation of tau that are enriched for genes and pathways previously implicated in AD pathology and overlap with co-expression networks identified in human AD cortex. Our data provide further evidence for an immune-response component in the accumulation of tau and reveal molecular pathways associated with the progression of AD neuropathology. : Castanho et al. use transgenic mice harboring human tau and amyloid precursor protein mutations to identify transcriptional changes associated with the progression of Alzheimer’s disease (AD) pathology. Their data support an immune-response component in the accumulation of tau and reveal molecular pathways associated with AD neuropathology. Keywords: tau, amyloid, transgenic model, Alzheimer’s disease, gene expression, neuropathology, entorhinal cortex, hippocampus, RNA-seq
Published: 2020
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14. Surveillance arterioveNous fistulAs using ultRasound (SONAR) trial in haemodialysis patients: a study protocol for a multicentre observational study

Author: Samantha Hyndman, Helena Edlin, Emma Laing, Edward CF Wilson, Subash Somalanka, James Hunter, James Richards, Mohammed Hossain, Dominic Summers, Matthew Slater, Matthew Bartlett, Vasilis Kosmoliaptsis, Regin Lagaac, Anna Sidders, Claire Foley, Valerie Hopkins, Chloe Fitzpatrick-Creamer, Cara Hudson, Sam Turner, Andrew Tambyraja, Sam Dutta, Sarah Lawman, Tracey Salter, Mohammed Aslam, Atul Bagul, Rajesh Sivaprakasam, George Smith, Zia Moinuddin, Simon Knight, Paul Gibbs, Reza Motallebzadeh, Nicholas Barnett, Gavin Pettigrew, Alison Deary, Veena Surendrakumar, Tobi Ayorinde, Igor Chipurovski, Subhankar Paul, Klaus Bond, Elizabeth Hardy, Joanne Widdup, Rachael Potter, Elisabeth Pugh, Karen Parsons, Kathryn Lafferty, Kate Crawford, Amy Bolsworth, Naavalah Ngwa-Ndifor, Rani Badhan, Anna Jerram, Jessica Lai, Joyce Banda, Janet Bendle, Maria Morgan, William Owen, Sue Dawson, Simon Daniel, Karen Allsop, Sarah-Jane Carmichael, Tom Eadie, Rona Lochiel, Midel Lena, Soundrie Padayachee, Philip Eldridge, May Rabuya, Jashree Patel, Abbas Ghazanfar, Judy Van Selm, Caroline Bodneck, Martia Augustin, Kwame Ansu, Nalin Khosla, Kashif Burney, Karen Dear, Carl Tiivas, Maria Truslove, Andrew Beech, Sarah Brand, Darren Cheal, Mel Smith, Kate Trivedi, Adnan Bajwa, John Kerr, Ana Fleet, Lianne Chapman, Sarah Gee, Thanuja Weerasinghe, Paris Cai, Judith Long, Tracey Rowe, Jeremy Crane, and Mary Quashie-Akponeware
Subjects: Medicine
Abstract: Introduction Arteriovenous fistulas (AVFs) are considered the best and safest modality for providing haemodialysis in patients with end-stage renal disease. Only 20% of UK centres achieve the recommended 80% target for achieving dialysis of the prevalent dialysis population via permanent access (as opposed to a central venous catheter). This is partly due to the relatively poor maturation rate of newly created fistulas, with as many as 50% of fistulas failing to mature.The Surveillance Of arterioveNous fistulAe using ultRasound study will examine whether a protocolised programme of Doppler ultrasound (US) surveillance can identify, early after creation, potentially correctable problems in those AVFs that subsequently fail to mature.Methods and analysis This is a multicentre observational study that will assess newly created AVFs by Doppler US performed at 2, 4, 6 and 10 weeks after creation. The primary outcome measure will be primary fistula patency at week 10. Secondary outcome measures include: successful use of the fistula; clinical suitability for dialysis; creation of new fistula or radiological salvage; fistula thrombosis; secondary fistula patency rate and patient acceptability.Ethics and dissemination The study has been approved by the Cambridgeshire and Hertfordshire Research Ethics Committee and by the Health Research Authority (REC 18/EE/0234). The results generated from this work will be published as open access, within 3 years of trial commencement. We will also present our findings at key national/international renal meetings, as well as support volunteers at renal patient groups to disseminate the trial outcome.Trial registration number ISRCTN36033877
Published: 2019
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15. A Systematic Evaluation of High-Throughput Sequencing Approaches to Identify Low-Frequency Single Nucleotide Variants in Viral Populations

Author: David J. King, Graham Freimanis, Lidia Lasecka-Dykes, Amin Asfor, Paolo Ribeca, Ryan Waters, Donald P. King, and Emma Laing
Subjects: high-throughput sequencing, viral populations, sub-consensus variants, sequencing error, Microbiology, QR1-502
Abstract: High-throughput sequencing such as those provided by Illumina are an efficient way to understand sequence variation within viral populations. However, challenges exist in distinguishing process-introduced error from biological variance, which significantly impacts our ability to identify sub-consensus single-nucleotide variants (SNVs). Here we have taken a systematic approach to evaluate laboratory and bioinformatic pipelines to accurately identify low-frequency SNVs in viral populations. Artificial DNA and RNA “populations” were created by introducing known SNVs at predetermined frequencies into template nucleic acid before being sequenced on an Illumina MiSeq platform. These were used to assess the effects of abundance and starting input material type, technical replicates, read length and quality, short-read aligner, and percentage frequency thresholds on the ability to accurately call variants. Analyses revealed that the abundance and type of input nucleic acid had the greatest impact on the accuracy of SNV calling as measured by a micro-averaged Matthews correlation coefficient score, with DNA and high RNA inputs (107 copies) allowing for variants to be called at a 0.2% frequency. Reduced input RNA (105 copies) required more technical replicates to maintain accuracy, while low RNA inputs (103 copies) suffered from consensus-level errors. Base errors identified at specific motifs identified in all technical replicates were also identified which can be excluded to further increase SNV calling accuracy. These findings indicate that samples with low RNA inputs should be excluded for SNV calling and reinforce the importance of optimising the technical and bioinformatics steps in pipelines that are used to accurately identify sequence variants.
Published: 2020
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16. Comparative Transcriptome Analysis of Streptomyces Clavuligerus in Response to Favorable and Restrictive Nutritional Conditions

Author: Laura Pinilla, León F. Toro, Emma Laing, Juan Fernando Alzate, and Rigoberto Ríos-Estepa
Subjects: transcriptomic analysis, Streptomyces clavuligerus, gene expression, clavulanic acid, complex media, gene cluster, Therapeutics. Pharmacology, RM1-950
Abstract: Background: Clavulanic acid (CA), a β-lactamase inhibitor, is industrially produced by the fermentation of Streptomyces clavuligerus. The efficiency of CA production is associated with media composition, culture conditions and physiological and genetic strain characteristics. However, the molecular pathways that govern CA regulation in S. clavuligerus remain unknown. Methods and Results: Here we used RNA-seq to perform a comparative transcriptome analysis of S. clavuligerus ATCC 27064 wild-type strain grown in both a favorable soybean-based medium and in limited media conditions to further contribute to the understanding of S. clavuligerus metabolism and its regulation. A total of 350 genes were found to be differentially expressed between conditions; 245 genes were up-regulated in favorable conditions compared to unfavorable. Conclusion: The up-regulated expression of many regulatory and biosynthetic CA genes was positively associated with the favorable complex media condition along with pleiotropic regulators, including proteases and some genes whose biological function have not been previously reported. Knowledge from differences between transcriptomes from complex/defined media represents an advance in the understanding of regulatory paths involved in S. clavuligerus’ metabolic response, enabling the rational design of future experiments.
Published: 2019
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17. OsdR of Streptomyces coelicolor and the Dormancy Regulator DevR of Mycobacterium tuberculosis Control Overlapping Regulons

Author: Mia Urem, Teunke van Rossum, Giselda Bucca, Geri F. Moolenaar, Emma Laing, Magda A. Świątek-Połatyńska, Joost Willemse, Elodie Tenconi, Sébastien Rigali, Nora Goosen, Colin P. Smith, and Gilles P. van Wezel
Subjects: Developmental control, Streptomyces, dormancy, stress response, Microbiology, QR1-502
Abstract: ABSTRACT Two-component regulatory systems allow bacteria to respond adequately to changes in their environment. In response to a given stimulus, a sensory kinase activates its cognate response regulator via reversible phosphorylation. The response regulator DevR activates a state of dormancy under hypoxia in Mycobacterium tuberculosis, allowing this pathogen to escape the host defense system. Here, we show that OsdR (SCO0204) of the soil bacterium Streptomyces coelicolor is a functional orthologue of DevR. OsdR, when activated by the sensory kinase OsdK (SCO0203), binds upstream of the DevR-controlled dormancy genes devR, hspX, and Rv3134c of M. tuberculosis. In silico analysis of the S. coelicolor genome combined with in vitro DNA binding studies identified many binding sites in the genomic region around osdR itself and upstream of stress-related genes. This binding correlated well with transcriptomic responses, with deregulation of developmental genes and genes related to stress and hypoxia in the osdR mutant. A peak in osdR transcription in the wild-type strain at the onset of aerial growth correlated with major changes in global gene expression. Taken together, our data reveal the existence of a dormancy-related regulon in streptomycetes which plays an important role in the transcriptional control of stress- and development-related genes. IMPORTANCE Dormancy is a state of growth cessation that allows bacteria to escape the host defense system and antibiotic challenge. Understanding the mechanisms that control dormancy is of key importance for the treatment of latent infections, such as those from Mycobacterium tuberculosis. In mycobacteria, dormancy is controlled by the response regulator DevR, which responds to conditions of hypoxia. Here, we show that OsdR of Streptomyces coelicolor recognizes the same regulatory element and controls a regulon that consists of genes involved in the control of stress and development. Only the core regulon in the direct vicinity of dosR and osdR is conserved between M. tuberculosis and S. coelicolor, respectively. Thus, we show how the system has diverged from allowing escape from the host defense system by mycobacteria to the control of sporulation by complex multicellular streptomycetes. This provides novel insights into how bacterial growth and development are coordinated with the environmental conditions.
Published: 2016
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18. Genome-wide analysis of in vivo binding of the master regulator DasR in Streptomyces coelicolor identifies novel non-canonical targets.

Author: Magdalena A Świątek-Połatyńska, Giselda Bucca, Emma Laing, Jacob Gubbens, Fritz Titgemeyer, Colin P Smith, Sébastien Rigali, and Gilles P van Wezel
Subjects: Medicine, Science
Abstract: Streptomycetes produce a wealth of natural products, including over half of all known antibiotics. It was previously demonstrated that N-acetylglucosamine and secondary metabolism are closely entwined in streptomycetes. Here we show that DNA recognition by the N-acetylglucosamine-responsive regulator DasR is growth-phase dependent, and that DasR can bind to sites in the S. coelicolor genome that have no obvious resemblance to previously identified DasR-responsive elements. Thus, the regulon of DasR extends well beyond what was previously predicted and includes a large number of genes with functions far removed from N-acetylglucosamine metabolism, such as genes for small RNAs and DNA transposases. Conversely, the DasR regulon during vegetative growth largely correlates to the presence of canonical DasR-responsive elements. The changes in DasR binding in vivo following N-acetylglucosamine induction were studied in detail and a possible molecular mechanism by which the influence of DasR is extended is discussed. Discussion of DasR binding was further informed by a parallel transcriptome analysis of the respective cultures. Evidence is provided that DasR binds directly to the promoters of all genes encoding pathway-specific regulators of antibiotic production in S. coelicolor, thereby providing an exquisitely simple link between nutritional control and secondary metabolism.
Published: 2015
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19. Differential producibility analysis (DPA) of transcriptomic data with metabolic networks: deconstructing the metabolic response of M. tuberculosis.

Author: Bhushan K Bonde, Dany J V Beste, Emma Laing, Andrzej M Kierzek, and Johnjoe McFadden
Subjects: Biology (General), QH301-705.5
Abstract: A general paucity of knowledge about the metabolic state of Mycobacterium tuberculosis within the host environment is a major factor impeding development of novel drugs against tuberculosis. Current experimental methods do not allow direct determination of the global metabolic state of a bacterial pathogen in vivo, but the transcriptional activity of all encoded genes has been investigated in numerous microarray studies. We describe a novel algorithm, Differential Producibility Analysis (DPA) that uses a metabolic network to extract metabolic signals from transcriptome data. The method utilizes Flux Balance Analysis (FBA) to identify the set of genes that affect the ability to produce each metabolite in the network. Subsequently, Rank Product Analysis is used to identify those metabolites predicted to be most affected by a transcriptional signal. We first apply DPA to investigate the metabolic response of E. coli to both anaerobic growth and inactivation of the FNR global regulator. DPA successfully extracts metabolic signals that correspond to experimental data and provides novel metabolic insights. We next apply DPA to investigate the metabolic response of M. tuberculosis to the macrophage environment, human sputum and a range of in vitro environmental perturbations. The analysis revealed a previously unrecognized feature of the response of M. tuberculosis to the macrophage environment: a down-regulation of genes influencing metabolites in central metabolism and concomitant up-regulation of genes that influence synthesis of cell wall components and virulence factors. DPA suggests that a significant feature of the response of the tubercle bacillus to the intracellular environment is a channeling of resources towards remodeling of its cell envelope, possibly in preparation for attack by host defenses. DPA may be used to unravel the mechanisms of virulence and persistence of M. tuberculosis and other pathogens and may have general application for extracting metabolic signals from other "-omics" data.
Published: 2011
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20. Effect of infrared heating on the nutritional properties of yellow pea and green lentil flours

Author: Emma Laing, Andrea K. Stone, Dai Shi, Mark Pickard, James D. House, Ning Wang, and Michael T. Nickerson
Subjects: Organic Chemistry, Food Science
Published: 2023

21. Effect of infrared heating on the functional properties of yellow pea and green lentil flours

Author: Emma Laing, Andrea K. Stone, Dai Shi, Mark Pickard, Ning Wang, and Michael T. Nickerson
Subjects: Organic Chemistry, Food Science
Published: 2023

22. Feasibility of the automatic ingestion monitor (AIM-2) for infant feeding assessment: a pilot study among breast-feeding mothers from Ghana

Author: Caroline Cerminaro, Edward Sazonov, Megan A McCrory, Matilda Steiner-Asiedu, Viprav Bhaskar, Sina Gallo, Emma Laing, Wenyan Jia, Mingui Sun, Tom Baranowski, Gary Frost, Benny Lo, and Alex Kojo Anderson
Subjects: Nutrition and Dietetics, Public Health, Environmental and Occupational Health, Medicine (miscellaneous)
Abstract: Objective:Passive, wearable sensors can be used to obtain objective information in infant feeding, but their use has not been tested. Our objective was to compare assessment of infant feeding (frequency, duration and cues) by self-report and that of the Automatic Ingestion Monitor-2 (AIM-2).Design:A cross-sectional pilot study was conducted in Ghana. Mothers wore the AIM-2 on eyeglasses for 1 d during waking hours to assess infant feeding using images automatically captured by the device every 15 s. Feasibility was assessed using compliance with wearing the device. Infant feeding practices collected by the AIM-2 images were annotated by a trained evaluator and compared with maternal self-report via interviewer-administered questionnaire.Setting:Rural and urban communities in Ghana.Participants:Participants were thirty eight (eighteen rural and twenty urban) breast-feeding mothers of infants (child age ≤7 months).Results:Twenty-five mothers reported exclusive breast-feeding, which was common among those < 30 years of age (n 15, 60 %) and those residing in urban communities (n 14, 70 %). Compliance with wearing the AIM-2 was high (83 % of wake-time), suggesting low user burden. Maternal report differed from the AIM-2 data, such that mothers reported higher mean breast-feeding frequency (eleven v. eight times, P = 0·041) and duration (18·5 v. 10 min, P = 0·007) during waking hours.Conclusion:The AIM-2 was a feasible tool for the assessment of infant feeding among mothers in Ghana as a passive, objective method and identified overestimation of self-reported breast-feeding frequency and duration. Future studies using the AIM-2 are warranted to determine validity on a larger scale.
Published: 2022

23. Reconstructing regulatory networks in Streptomyces using evolutionary algorithms.

Author: Spencer Angus Thomas, Yaochu Jin, Emma Laing, and Colin P. Smith
Published: 2013
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24. Virological Characterization of Critically Ill Patients With COVID-19 in the United Kingdom: Interactions of Viral Load, Antibody Status, and B.1.1.7 Infection

Author: Tanya Golubchik, Anthony C. Gordon, Rutger J. Ploeg, Ullrich Leuscher, Wendy Slack, Pat Tsang, Manu Shankar-Hari, David K. Menon, Paul R Mouncey, Sarah Williams, Lise J Estcourt, Sheba Ziyenge, Farah Al-Beidh, Heli Harvala, Nick A Ciccone, Peter Simmonds, David J. Roberts, Jeremy Ratcliff, Kathryn M Rowan, Abigail Lamikanra, Jennifer Rynne, Amy Evans, Dung Nguyen, Aislinn Jennings, Matthew Fish, Emma Laing, David Bonsall, and Marta S Oliveira
Subjects: Male, 0301 basic medicine, Critical Illness, medicine.disease_cause, SARS-CoV-2/immunology, Immunoglobulin G, Serology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Intensive care, Humans, Immunology and Allergy, Medicine, Antibodies, Viral/immunology, 030212 general & internal medicine, Seroconversion, Immunoglobulin G/immunology, Aged, Coronavirus, Serologic Tests/methods, biology, business.industry, Viral Load/immunology, Immunization, Passive, Middle Aged, RNA, Viral/immunology, Antibodies, Neutralizing/immunology, United Kingdom, 3. Good health, COVID-19/immunology, 030104 developmental biology, Infectious Diseases, Immunology, biology.protein, Female, Spike Glycoprotein, Coronavirus/immunology, Antibody, business, Viral load
Abstract: BackgroundConvalescent plasma containing neutralizing antibody to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is under investigation for coronavirus disease 2019 (COVID-19) treatment. We report diverse virological characteristics of UK intensive care patients enrolled in the Immunoglobulin Domain of the REMAP-CAP randomized controlled trial that potentially influence treatment outcomes.MethodsSARS-CoV-2 RNA in nasopharyngeal swabs collected pretreatment was quantified by PCR. Antibody status was determined by spike-protein ELISA. B.1.1.7 was differentiated from other SARS-CoV-2 strains using allele-specific probes or restriction site polymorphism (SfcI) targeting D1118H.ResultsOf 1274 subjects, 90% were PCR positive with viral loads 118–1.7 × 1011IU/mL. Median viral loads were 40-fold higher in those IgG seronegative (n = 354; 28%) compared to seropositives (n = 939; 72%). Frequencies of B.1.1.7 increased from ConclusionsHigh viral loads in seropositive B.1.1.7-infected subjects and resistance to seroconversion indicate less effective clearance by innate and adaptive immune responses. SARS-CoV-2 strain, viral loads, and antibody status define subgroups for analysis of treatment efficacy.
Published: 2021

25. 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, Rebekah Baldwin-Jones, James Balfour, Gagan Bali, Sonya Balkee, Ceri Ball, Kasia Ballard, Amy Ballinger, Ismael Balluz, Craig Balmforth, Emese Balogh, Amir Baluwala, Gabby Bambridge, Alasdair Bamford, Amy Bamford, Peter Bamford, Adefunke Bamgboye, Elizabeth Bancroft, Hollie Bancroft, Tanya Bancroft, Joyce Banda, Krishna Bandaru, Srini Bandi, Nageswar Bandla, Somaditya Bandyopadhyam, Amit Banerjee, Millie Banerjee, Ritwik Banerjee, Harrison Banks, Lauren Banks, Luke Banks, Paul Banks, Oliver Bannister, Bharat Bansal, Robert Banthorpe, Laura Banton, Mariamma Baptist, Tanya Baqai, Ananya Mouli Baral, Desislava Baramova, Alex Barber, Russel Barber, Emma Barbon, Miriam Barbosa, Monica Barbosa, Jamie Barbour, Alexander Barclay, Claire Barclay, George Bardsley, Stephanie Bareford, Shahedal Bari, Amy Barker, Debbie Barker, Helen Barker, Joseph Barker, Leon Barker, Oliver Barker, Kerry Barker-Williams, Sinha Barkha, Juliana Barla, Gavin Barlow, Richard Barlow, Valerie Barlow, James Barnacle, Alex Barnard, Debi Barnes, Nicky Barnes, Theresa Barnes, Calum Barnetson, Amy Barnett, Matthew Barnett, Ashton Barnett-Vanes, William Barnsley, Andrew Barr, David Barr, Shaney Barratt, Manuella Barrera, Amy Barrett, Fiona Barrett, Jessica Barrett, Joe Barry, Jazz Bartholomew, Claire Bartlett, Georgina Bartlett, Greg Barton, Jill Barton, Lorna Barton, Rachael Barton, Rosaleen Baruah, Sonia Baryschpolec, Archana Bashyal, Betsy Basker, Ayten Basoglu, Gilda Bass, John Bassett, G Bassett, Chris Bassford, Pavinder Bassi, Betsy Bassis, Bengisu Bassoy, Victoria Bastion, Anupam Basumatary, Tristan Bate, Harry J Bateman, Ian Bateman, Kathryn Bateman, Vhairi Bateman, Eleanor Bates, Hayley Bates, Michelle Bates, Simon Bates, Sally Batham, Ana Batista, Amit Batla, Dushyant Batra, Donna Batty, Harry Batty, Thomas Batty, Peter Baughan, Miranda Baum, Carina Bautista, Fareha Bawa, Fatima S Bawani, Simon Bax, Lydia Baxter, Matt Baxter, Nicola Baxter, Zachary Baxter, Hannah Bayes, Charlotte Baylem, Lee Bayliss, Eileen Bays, Farid Bazari, Rohit Bazaz, Ahmad Bazli, Laura Beacham, Wendy Beadles, Philip Beak, Andy Beale, Kirk Beard, Jack Bearpark, Karen Beaumont, Dawn Beaumont-Jewell, Theresa Beaver, Sarah Beavis, Christy Beazley, Sarah Beck, Virginia Beckett, Rosie Beckitt, Heidi Beddall, Seonaid Beddows, Deborah Beeby, Gail Beech, Michelle Beecroft, Sally Beer, Jane Beety, Gabriela Bega, Alison Begg, Susan Begg, Sara Beghini, Ayesha Begum, Salman Begum, Selina Begum, Teresa Behan, Jasmine Beharry, Roya Behrouzi, Jon Beishon, Claire Beith, James Belcher, Holly Belfield, Katherine Belfield, Ajay Belgaumkar, Dina Bell, Gareth Bell, Gill Bell, Gillian Bell, Joshua Bell, Lauren Bell, Louise Bell, Nicholas Bell, Pippa Bell, Stephanie Bell, Jennifer L Bell, Jennifer Bellamu, Mary Bellamy, Arianna Bellini, Amanda Bellis, Fionn Bellis, Lesley Bendall, Naveena Benesh, Nicola Benetti, Leonie Benham, Guy Benison-Horner, Alexander Bennett, Ann Bennett, Caroline Bennett, Christopher Bennett, Gillian Bennett, Ian Bennett, Kristopher Bennett, Lorraine Bennett, Sara Bennett, Karen Bennion, Vivienne Benson, Jane Benstead, Andrew Bentley, Dionne Bentley, James Bentley, Ian Benton, Eva Beranova, Matthew Beresford, Colin Bergin, Malin Bergstrom, Jolanta Bernatoniene, Thomas Berriman, Zoe Berry, Marnie Berwick, Kimberley Best, Ans-Mari Bester, Yvonne Beuvink, Emily Bevan, Sarah Bevins, Tom Bewick, Andrew Bexley, Sonay Beyatli, Fenella Beynon, Arjun Bhadi, Sanjay Bhagani, Shiv Bhakta, Rekha Bhalla, Khushpreet Bhandal, Kulbinder Bhandal, Ashwin Bhandari, Sangam Bhandari, Aashutosh Bhanot, Ravina Bhanot, Sruti Bhaskara, Prashanth Bhat, Nikhil Bhatia, Rahul Bhatnagar, Karan Bhatt, Janki Bhayani, Deepika Bhojwani, Salimuzzaman Bhuiyan, Anna Bibby, Fatima Bibi, Naheeda Bibi, Salma Bibi, Tihana Bicanic, Sarah Bidgood, Julie Bigg, Sarah Biggs, Alphonsa Biju, Andras Bikov, Sophie Billingham, Jessica Billings, Carron Bilton, Teodirico Binas, Martin Binney, Alice Binns, Muhammad BinRofaie, Oliver Bintcliffe, Catherine Birch, Jenny Birch, Louann Birch, Janet Birchall, Katherine Birchall, Sam Bird, Sumedha Bird, Charndip Biring, Mark Birt, Raquel Bisa, Kilanalei Bishop, Linda Bishop, Lisa Bishop, Karen Bisnauthsing, Nibedan Biswas, Sahar Biuk, Karen Blachford, Ethel Black, Helen Black, Karen Black, Mairead Black, Polly Black, Hayley Blackgrove, Bethan Blackledge, Joanne Blackler, Samantha Blackley, Helen Blackman, Stuart Blackmore, Caroline Blackstock, Loraine Blackwood, Francesca Blakemore, Helen Blamey, Alison Bland, Sujata Blane, Simon Blankley, Mary Blanton, Parry Blaxill, Jenny Blaxland, Katie Blaylock, Jane Blazeby, Carol Blears, Natalie Blencowe, Donna Blofield, Ben Bloom, Jack Bloomfield, Angela Bloss, Hannah Bloxham, Louise Blundell, Andrew Blunsum, Mark Blunt, Ian Blyth, Kevin Blyth, Andrew Blythe, Karen Blythe, Marilyn Boampoaa, Boniface Bobie, Karen Bobruk, Pritesh Bodalia, Neena Bodasing, Tanya Bodenham, Sherin Bodh, Gabriele Boehmer, Marta Boffito, Kristyna Bohmova, Sumit Bokhandi, Maria Bokhar, Saba Bokhari, Sakina Bokhari, Syed Owais Bokhari, Ambrose Boles, Sarah Bollington, Sam Bolton, Charlotte Bomken, Charlotte Bond, Hayley Bond, Helena Bond, Stuart Bond, Thomas Bond, Alice Bone, Georgia Boniface, Wendy Bonnert, Lizzy Bonney, Leigh Boorman, Catherine Booth, Joanne Borbone, Cameron Borhani, Naomi Borman, Rachel Borrell, Mamu Boshir, Fiona Bottrill, Laura Bough, Hayley Boughton, Zoe Boult, Miriam Bourke, Stephen Bourke, Michelle Bourne, Rachel Bousfield, Lucy Boustred, Darren Bowen, Kaye Bowen, Alexandra Bowes, Amy Bowes, Philip Bowker, Louise Bowman, Simon Bowman, Rachel Bowmer, Angie Bowring, Geoff Bowyer, Helen Bowyer, Carmel Boyd, Jenny Boyd, Laura Boyd, Maxine Boyd, Namoi Boyle, Pauline Boyle, Rosalind Boyle, Louise Boyles, Osman Bozdag, Leanna Brace, David Brack, Charlotte Brackstone, Rob Bradburn, Jodie Bradder, Barry Bradley, Clare Jane Bradley, Pamela Bradley, Patrick Bradley, Paul Bradley, Joanne Bradley-Potts, Lynne Bradshaw, Sarah Bradshaw, Zena Bradshaw, Rebecca Brady, Shirin Brady, Denise Braganza, Suhail Brailsford, Jill Braithwaite, Marie Branch, Thomas Brankin-Frisby, Jamie Brannigan, Louise Brassington, Sophie Brattan, Fiona Bray, Nancy Bray, Angela Brazier, Manny Brazil, Lucy Brear, Tracy Brear, Stephen Brearey, Laura Bremner, Morwenna Brend, Giovanna Bretland, Chris Brewer, Hannah Bridge, Gavin Bridgwood, Hayley Briggs, Mark Briggs, Sara Brigham, John Bright, Chris Brightling, Lutece Brimfield, Elaine Brinkworth, Robin Brittain-Long, Vianne Britten, Terri Brittin, Lauren Broad, Sarah Broad, Rosie Broadhurst, Andrew Broadley, Marie Broadway, Christopher Brockelsby, Megan Brocken, Tomos Brockley, Andrew Broderick, Mary Brodsky, Fiona Brogan, David Broggio, Liz Brohan, Felicity Brokke, Jacob Brolly, David Bromley, Hannah Brooke-Ball, Verity Brooker, Ceri Brookes, Matthew Brookes, Alison Brooks, Karen Brooks, Nicole Brooks, Philip Brooks, Rachel Brooks, Sophie Brooks, Natalie Broomhead, Chloe Broughton, Nathaniel Broughton, Matt Brouns, Marie Browett, Alison Brown, Ammani Brown, Carly Brown, Catrin Brown, Chloe Brown, Elizabeth Brown, Ellen Brown, Heather Brown, Janet Brown, Louise Brown, Niall Brown, Pauline Brown, Rachel Brown, Richard Brown, Robert Brown, Steven Brown, Tom Brown, Wayne Brown, Bria Browne, Charlotte Browne, Duncan Browne, Mitchell Browne, Stephen Brownlee, Alba Brraka, David Bruce, Johanna Bruce, Michelle Bruce, Wojciech Brudlo, Nigel Brunskill, Alan Brunton, Margaret Brunton, Mandy Bryan, Meera Bryant, April Buazon, Maya Buch, Julie Buchan, Ruaridh Buchan, Alexis Buchanan, Ruaridh Buchanan, Danielle Buche, Amanda Buck, Matthew Buckland, Laura Buckley, Philip Buckley, Sarah Buckley, Carol Buckman, Kathleen Buckmire, George Bugg, Ramadan Bujazia, Marwan Bukhari, Shanze Bukhari, Richard Bulbulia, Alex Bull, Damian Bull, Rhian Bull, Thomas Bull, Naomi Bulteel, Kasun Bumunarachchi, Roneleeh Bungue-Tuble, Caroline Burchett, Dorota Burda, Christy Burden, Thomas G Burden, Mika Burgess, Paula Burgess, Richard Burgess, Sophia Burgess, Paula Burgett, Adrian Burman, Sara Burnard, Caroline Burnett, John Burnett, Amanda Burns, Amy Burns, Collette Burns, James Burns, Karen Burns, Samuel Burns, Sarah Burns, Daniel Burrage, Sadie Burrage, Kate Burrows, Claire Burston, Ben Burton, Fiona Burton, Matthew Burton, Angela Busby, Deborah Butcher, Aaron Butler, Jessica Butler, Joanne Butler, Joshua Butler, Lesley Butler, Peter Butler, Susan Butler, Al-Tahoor Butt, Mohammad M Butt, Sophia Butt, Caryl Butterworth, Nicola Butterworth-Cowin, Robert Buttery, Tom Buttle, Heather Button, Daniel Buttress, Jane Byrne, Wendy Byrne, Victoria Byrne-Watts, Eleanor Byworth, Amanda Cabandugama, Ruth Cade, Anthony Cadwgan, Donna Cairney, James Calderwood, Darren Caldow, Moira Caldwell, Giorgio Calisti, Debbie Callaghan, Jennifer Callaghan, Claire Callens, Donaldson Callum, Caroline Calver, Melissa Cambell-Kelly, Tracey Camburn, David R Cameron, Eleanor Cameron, Fraser Cameron, Sarah 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 Carter-Graham, Douglas Cartwright, Jo-Anne Cartwright, Claire Carty, Sinead Carty, Jaime Carungcong, Carolyn Carveth-Marshall, Susan Casey, Annie Cassells, Barbara Cassimon, Teresa Castiello, Gail Castle, Bridget Castles, Melanie Caswell, Ana Maria Catana, Heidi Cate, Susanne Cathcart, Katrina Cathie, Christine Catley, Laura Catlow, Matthew Caudwell, Jill Caulfield, Anna Cavazza, Luke Cave, Simon Cavinato, Frianne Cawa, Kathryn Cawley, Chloe Caws, Hankins Cendl, Hannah Century, Jeva Cernova, Mansur Cesay, Ed Cetti, Stephanie Chabane, Manish Chablani, Cathleen Chabo, David Chadwick, Julie Chadwick, Robert Chadwick, Ela Chakkarapani, Arup Chakraborty, Mallinath Chakraborty, Mollika Chakravorty, James Chalmers, Richard Chalmers, Georgina Chamberlain, Sarah Chamberlain, Emma Chambers, Jonathan Chambers, Lucy Chambers, Naomi Chambers, Alex Chan, Carmen Chan, Cheuk Chan, Evelyn Chan, Kayen Chan, Kimberley Chan, Ping Chan, Rebekah (Pui-Ching) Chan, Xin Hui Chan, Chris Chandler, Heidi Chandler, Kim J Chandler, Stuart Chandler, Zoe Chandler, Vikki Chandler-Vizard, Sumit Chandra, Navin Chandran, Badrinathan Chandrasekaran, Cherry Chang, Yvonne Chang, Josephine Chaplin, Graeme Chapman, John Chapman, Katie Chapman, Laura Chapman, Lianne Chapman, Polly Chapman, Timothy Chapman, Lucy Chappell, Linda Chapple, Amanda Charalambou, Bethan Charles, Dianne Charlton, Sally Charlton, Kevin Chatar, Calvin Chatha, Ritesh Chaube, Muhammad YN Chaudhary, Iram Chaudhry, Nazia Chaudhuri, Muhammad Chaudhury, Anoop Chauhan, Ruchi S Chauhan, Vipul Chauhan, Nicola Chavasse, Iknam Chaven, Rosanna Chavez, Vipal Chawla, Maria Cheadle, Lindsay Cheater, James Cheaveau, Charlotte Cheeld, Michelle Cheeseman, Fang Chen, Hui Min Chen, Terence Chen, Lok Yin Cheng, Zhihang Cheng, Helen Chenoweth, Chun How Cheong, Shiney Cherian, Suzanne Cherif, Mary Cherrie, Helen Cheshire, Barry Chesterson, Betty Cheung, Chee Kay Cheung, Elaine Cheung, Michelle Cheung, Claire Cheyne, Swati Chhabra, Wei Ling Chia, 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, Diane Clark, Felicity Clark, Gabrielle Clark, James Clark, Katherine Clark, Kaylea Clark, Louise Clark, Lucy Clark, Matthew Clark, Patricia Clark, Richard Clark, Thomas Clark, Wendy Clark, Zoe Clark, Andrea Clarke, Heather Clarke, Mark Clarke, Paul Clarke, Robert Clarke, Roseanne Clarke, Samantha Clarke, Sarah Clarke, Sheron Clarke, Tracy Clarke, Andrew Clarkson, Alleyna Claxton, Kate Clay, Elizabeth Clayton, Olivia Clayton, Jill Clayton-Smith, Chris Cleaver, Carlota Clemente de la Torre, Jayne Clements, Suzanne Clements, Francesca Clemons, Lee Clifford, Lynne Clifford, Rachael Clifford, Sarah Clifford, Amelia Clive, Jonathan Clouston, Samantha Clueit, Andrea Clyne, Michelle Coakley, Peter G L Coakley, Tony Coates, Kathryn Cobain, Alexandra Cochrane, Patricia Cochrane, Maeve Cockerell, Helen Cockerill, Shirley Cocks, Rachel Codling, Adam Coe, Samantha Coetzee, David Coey, Danielle Cohen, Jonathan Cohen, Oliver Cohen, Mike Cohn, Louise Coke, Olutoyin Coker, Nicholas Colbeck, Roghan Colbert, Carol Cole, Esther Cole, Jade Cole, Joby Cole, Julie Cole, Richard Cole, Sue Cole, Garry Coleman, Matt Coleman, Holly Coles, Rebecca Coles, Macleod Colin, Alicia Colino-Acevedo, Julie Colley, Dawn Collier, Heather Collier, Paul Collini, Emma Collins, Jaimie Collins, Joanne Collins, Nicola Collins, Sally Collins, Vicky Collins, Andrew Collinson, Bernadette Collinson, Jennifer Collinson, Matthew Collis, Madeleine Colmar, Hayley E Colton, James Colton, Katie Colville, Carolyn Colvin, Ryan Colwell, Edward Combes, David Comer, Alison Comerford, Mike Comery, Dónal Concannon, Robin Condliffe, Lynne Connell, Natalie Connell, Karen Connelly, Gavin Connolly, Mireille Connolly, Emma Connor, Samantha Conran, Antonia Conroy, Veronica Conteh, Rory Convery, Camilla Conway, Francesca Conway, Grainne Conway, Rhiannon Conway, Jo-Anna Conyngham, Colette Cook, Eloise Cook, Gemma Cook, Helen Cook, Julie Cook, Danielle Cooke, Graham Cooke, Katrina Cooke, Soo Cooke, Tim Cooke, Adele Cooper, Alison Cooper, Chris Cooper, David Cooper, Helen Cooper, Jamie Cooper, Joanne Cooper, Joshua Cooper, Laura Cooper, Lauren Cooper, Nick Cooper, Rowena Cooper, Emma Cooperwaite, Thomas Cope, Sinead Corbet, Carolyn Corbett, John Corcoran, Chris Cordell, Jessica Cordle, Alasdair Corfield, John Corless, Alison Corlett, Joe Cornwell, Michael Cornwell, Diana Corogeanu, Mirella Corredera, Ruth Corrigan, Catherine Corry, Rita Corser, Denise Cosgrove, Tracey Cosier, Patricia Costa, Charlie Coston, Susannah Cotgrove, Zoe Coton, Lisa-Jayne Cottam, Rhiannon Cotter, Donna Cotterill, Alice Cotton, Caroline Cotton, Katy Cotton, Andrew Coull, James Coulson, David Counsell, David Counter, Cherry Coupland, Ellie Courtney, Julia Courtney, Rebecca Cousins, Alexander Cowan, Elena Cowan, Ruth Cowburn, Richard Cowell, Louise Cowen, Steve Cowman, Amanda Cowton, Debra Anne Cox, Ellie Cox, Giles Cox, Karina Cox, Miriam Cox, Karen Coy, Beverly Craig, Victoria Craig, Felicity Craighead, Matthew Cramp, Beverley Crane, Jacolene Crause, Adrian Crawford, Angie Crawford, Emma Crawford, Isobel Crawford, Richard Crawforth, Sarah Crawshaw, Ben Creagh-Brown, Andrew Creamer, Ryan Creighton, Joanne Cremona, Saveria Cremona, Janet Cresswell, Mark Cribb, Charles Crichton, Declan Crilly, Lauren Crisp, Nikki Crisp, Dominic Crocombe, Maria Croft, Ian Cron, Derrick Crook, Jennifer Crooks, Helen Croot, Harriet Crosby, Sarah Cross, Tim Cross, Amy Crothers, Stephen Crotty, Susan Crouch, Madeleine Crow, Amanda Crowder, Kate Crowley, Teresa Crowley, Rebecca Croysdill, Callum Cruickshank, Conor Cruickshank, Irena Cruickshank, James Cruise, Helen Crumley, Carina Cruz, Trino Cruz Cervera, Dominic Cryans, Guanguo Cui, Helen Cui, Donna Cullen, Lorraine Cullen, Gillian Cummings-Fosong, Marie Cundall, Victoria Cunliffe, Lorraine Cunningham, Neil Cunningham, Nicola Cunningham, Jason Cupitt, Hollie Curgenven, Debra Curley, Gerens Curnow, David Curran, Simon Curran, Craig Currie, Jacqueline Currie, Scarlett Currie, Abi Curtis, Becca Curtis, Jonathan Curtis, Katrina Curtis, Olivia Curtis, Thomas Curtis, Rebecca Cuthbertson, Sean Cutler, Marta Czekaj, Patrycja Czylok, Joana da Rocha, Andrew Dagens, Helen Daggett, Phil Daggett, Jacqui Daglish, Sandeep Dahiya, Helen Dakers-Black, Anne Dale, Katie Dale, Michaela Dale, Sam Dale, Jolyon Dales, Helen Dalgleish, Nikki Dallas, Helen Dallow, Dermot Dalton, Zoe Daly, Akila Danga, Amelia Daniel, Priya Daniel, Allison Daniels, Adela Dann, Sandra Danso-Bamfo, Nimo Daoud, Alex Darbyshire, Janet Darbyshire, Paul Dargan, Paul Dark, Tace Darling, Kate Darlington, Tom Darton, Guledew Darylile, Manjusha Das, Sukamal Das, Martin Daschel, Joanne Dasgin, Dibyendu Datta, Anna Daunt, Emily Davenport, Mark Davey, Michelle Davey, Miriam Davey, Molly Davey, Arlene David, Mini David, Alexander Davidson, Laura Davidson, Neil Davidson, Richard Davidson, Albert Davies, Alison Davies, Amanda Davies, Amy Davies, Angela Davies, Carolyn Davies, Catrin Davies, Cheryl Davies, Drew Davies, Elaine Davies, Ffyon Davies, Helen Davies, James Davies, Jane Davies, Jeni Davies, Jim Davies, Karen Davies, Kelly Davies, Kim Davies, Louisa Davies, Mark Davies, Matthew Davies, Michelle Davies, Nina Davies, Owen Davies, Patrick Davies, Rachel Davies, Rhys Davies, Ruth Davies, Sarah Davies, Simon Davies, Alison Davis, Gwyneth Davis, Illinos Davis, Julie-Ann Davis, Katherine Davis, Peter Davis, Alexander Davison, Sophia Davison, Mark Davy, Christine Dawe, H Dawe, Mark Dawkins, Danielle Dawson, Elizabeth Dawson, Joy Dawson, Susan Dawson, Tom Dawson, Andrew Daxter, Andrew Day, Helena Day, Jacob Day, Jeremy Day, Lynn Day, Jamie D'Costa, Parijat De, Duneesha de Fonseka, Toni de Freitas, Frederico De Santana Miranda, Eleanor de Sausmarez, Shanika de Silva, Thushan de Silva, Jessica De Sousa, Paulo De Sousa, James de Souza, Anthony de Soyza, Natasha de Vere, Johannes de Vos, Bethan Deacon, Sharon Dealing, Anna Dean, Julie Dean, Katrina Dean, Stephen Dean, Tessa Dean, Jill Deane, James Dear, Effie 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 Downey, Robert Downey, Louise Downs, Simon Dowson, Cornel Dragan, Cristina Dragomir, Cristina Dragos, Maire Drain, Chelsea Drake, Victoria Drew, Olivia Drewett, Celine Driscoll, Helena Drogan, Nikki Drogman, Graham Drummond, Ronald Druyeh, Simon Drysdale, An Du Thinh, Hazel Dube, Judith Dube, Ophias Dube, Stephen Duberley, Hayley Duckles-Leech, Nicola Duff, Emma Duffield, Sam Duff-Miller, Helen Duffy, Lionel Dufour, Annette Duggan, Helen Duggan, Parveen Dugh, Janice Duignan, Mick Duley, Simon Dummer, Andrew Duncan, Christopher Duncan, Fullerton Duncan, Gregory Duncan, Stephanie Dundas, Alessia Dunn, Charlotte Dunn, Damian Dunn, Laura Dunn, Paul Dunn, Charlene Dunne, Karen Dunne, Fiona Dunning, Aidan Dunphy, Venkat Duraiswamy, Beatriz Duran, Ingrid DuRand, Steve Durgacharan, Natalie Duric, Alison Durie, Emily Durie, Hannah Durrington, Haris Duvnjak, Akshay Dwarakanath, Laasya Dwarakanath, Ellen Dwyer, Claudia Dyball, Lee Dyble, Kristyn Dyer, Harvey Dymond, Tom Dymond, Chris Eades, Laura 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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, Matthew Grant, Pauleen Grant, Rhys Gravell, Jenny Graves, Alasdair Gray, Catherine Gray, Georgina Gray, Harriet Gray, Ingrid Gray, Jackie Gray, Karen Gray, Nicola Gray, Sebastian Gray, Alan Grayson, Patricia Grealish, Fiona Greaves, Jack Greaves, Paul Greaves, Charlotte Green, Christopher Green, David Green, Frederick Green, Grace Green, Joel Green, Marie Green, Nicola Green, Stacey Green, Teresa Green, Diarra Greene, Philippa Greenfield, Alan Greenhalgh, Maraneka Greenslade, Daniel Greenwood, Sandra Greer, James Gregory, Jane Gregory, Katie Gregory, Tamsin Gregory, James Gregson, Jill Greig, Julia Greig, Rebecca Grenfell, Teena Grenier, Susan Grevatt, Glaxy Grey, Andrew Gribbin, Amy Gribble, Beverley Grice, Natasha Grieg, Douglas Grieve, Ben Griffin, Denise Griffin, Mel Griffin, Sian Griffith, Alexandra Griffiths, Andrew Griffiths, Daniel Griffiths, David Griffiths, Donna Griffiths, Isabel Griffiths, Mark Griffiths, Nicola Griffiths, Oliver Griffiths, Sarah Griffiths, Sharon 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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Hill, Phoebe Hill, Uta Hill, Annette Hilldrith, Elizabeth Hillerby, Catherine Hillman-Cooper, Elisabeth Hilton, Zoe Hilton, Sarah Hinch, Marcus Hinde, Andrew Hindle, Alice Hindmarsh, Paul Hine, Kim Hinshaw, Clare Hird, Alison Hirst, Jemma Hives, Benson Ho, Michaela Hoare, David Hobden, Gill Hobden, Maria Hobrok, Simon Hobson, Renate Hodge, Simon Hodge, Lesley Hodgen, Holly Hodgkins, Louise Hodgkinson, Sally Hodgkinson, David Hodgson, Helen Hodgson, Luke Hodgson, Sheila Hodgson, Gemma Hodkinson, Kenneth Hodson, Matthew Hogben, Lucy Hogg, Lee Hoggett, Abigail Holborow, Catherine Holbrook, Catherine Holden, Melinda Holden, Thomas Holder, Niels Holdhof, Hannah Holdsworth, Lisa Holland, Maureen Holland, Nicky Holland, Marie Hollands, Elizabeth Holliday, Nina Holling, Gillian Hollis, Laszlo Hollos, Linda Holloway, Simon Holloway, Marcus Hollyer, Amy Holman, Ann Holmes, Benjamin Holmes, Megan Holmes, Raphael Holmes, Rebecca Holmes, Kelly Holroyd, Caroline Holt, Lyndsey Holt, Siobhan Holt, 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 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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 Leandro, Darren Leaning, Sandra Leason, Christina Leaver, Marie Anne Ledingham, Emma Lee, Hannah Lee, Irish Lee, Judith Lee, Sam Lee, Shi Han Lee, Simon Lee, Sindy Lee, Stephanie Lee, Tracey Lee, Xiang Lee, Diana Lees, Jennifer Lees, Helen Legge, Julian Leggett, Katie Leigh-Ellis, Kevan Leighton, Nicky Leitch, Eleni Lekoudis, Petula Lemessy, Nicholas Lemoine, Joana Lemos, Irina Lenchuk, Katy Leng, Katrina Lennon, Liz Lennon, Isabel Lentell, Kelly Leonard, Wen Leong, Nicky Leopold, Oskar Lepiarczyk, Isla Leslie, Eleni Lester, Joe Leung, Ullrich Leuschner, Emma Levell, Chris Levett, Alice Lewin, Michaela Lewin, Alison Lewis, David Lewis, Dee Lewis, Georgina Lewis, Gillian Lewis, Joanne Lewis, Joseph Lewis, Kathryn Lewis, Keir Lewis, Leon Lewis, Lisa Lewis, Marissa Lewis, Rob Lewis, Robert Lewis, Catherine Lewis-Clarke, Lorraine Lewis-Prosser, Katherine Lewiston, Adam Lewszuk, Penny Lewthwaite, Samantha Ley, Anna Li, Jenny Li, Angela Liao, Victoria Licence, David Lieberman, Susan Liebeschuetz, Nicky Lightfoot, Patrick Lillie, Ben Lim, Carys Lim, Ee Thong Lim, Ivy Lim, Terence Lim, Wei Shen Lim, Wilson Lim, James Limb, Usha Limbu, Christian Linares, Dermot Linden, Gabriella Lindergard, Kate Lindley, Charlotte Lindsay, Emily Lindsay, Max Lindsay, Helen Lindsay-Clarke, Mirella Ling, Claire Lingam, Linette Linkson, Mike Linney, Louise Linsell, Conrad Lippold, George Lipscomb, Karen Lipscomb, Laura Lipskis, Ana Lisboa, Evangeline Lister, Charlotte Little, Jeff Little, Sam Little, Xuedi Liu, Alexandra Liversidge, Jill Livingstone, Daniel K Llanera, Rhiannon Llewellyn, Martin Llewelyn, Adam Lloyd, Aimee Lloyd, Arwel Lloyd, Oliver Lloyd, Richard Lloyd, Su Lo, David Loader, Cristina Lobato, Maria Lobo-Clarke, Lydianne Lock, Sara Lock, Stephen Lock, Angela Locke, Jacqueline Locke, Thomas Locke, Teresa Lockett, Sandy Lockyer, Jeorghino Lodge, Terrence Lodge, Martina Lofthouse, Tracey Lofting, Heather Loftus, Meg Logan, Chloe Logue, Sook Yin Loh, Siddharth Lokanathan, Kaatje Lomme, Emily London, Gabriella Long, Natalie Long, Bev Longhurst, Mark Longshaw, Jennifer Lonnen, Caroline Lonsdale, Laura Looby, Ronda Loosley, Paola Lopez, Paula Lopez, Robert Lord, Stuart Lord, Laura Lordache, Kieron Loregnard, Catherine Lorenzen, Claire Lorimer, Francesco Loro, Rachel Lorusso, Eva Loutraris, Robert Loveless, Maxine Lovell, Angeliki Loverdou, Huw Lovett, Daniel Loveys, Andrew Low, Jen Mae Low, Alastair Lowe, Caroline Lowe, Catherine Lowe, Emily Lowe, Faye Lowe, Michael Lowe, Linda Lowrey, Richard Lowsby, Vicki Lowthorpe, Emma Loxley, Gamu Lubimbi, Alexandra Lubina Solomon, Georgia Lucas, Jacob Lucas, Alice Lucey, Olivia Lucey, Suzanne Luck, H Luke, Jane Luke, Hayley Lund, Apurva Lunia, Muriel Lunn, Ji Luo, Julia Lussier, Cindy Nisha Luximon, Elisa Ly, Barrie Lyell, Elisavet Lyka, Sarah Lymn, Audrey Lynas, Ceri Lynch, Daniel Lynch, Daniella Lynch, Stephen Lynch, Helen Lyon, Rea-Grace Maamari, Hannah Mabb, Louies Mabelin, Jessica Macaro, Angela Macauley, 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, Thushika Mahendiran, Siva Mahendran, Sarah Maher, Anistta Maheswaran, Shameera Maheswaran, Tina Maheswaran, Parisa Mahjoob-Afag, Ahmed Mahmood, Farhana Mahmood, Waheed Mahmood, Zahra Mahmood, Hager Mahmoud, Ewan Mahony, Luke Mair, Toluwani Majekdunmi, Kesson Majid, Rupert Major, Jaydip Majumdar, Mohammad KH Majumder, Stephen Makin, Marius Malanca, Hannah Malcolm, Flora Malein, Neeraj Malhan, Ayesha Malik, Gulshan Malik, Mohammed Maljk, Paul Mallett, Petrina Mallinder, Georgia Mallison, Louise Mallon, Edward Malone, Gracie Maloney, Edgar Malundas, Madhu Mamman, Irene Man, Kathy Man, Rossana Mancinelli, Marco Mancuso-Marcello, Tracy Manders, Lauren Manderson, Justin Mandeville, Roope Manhas, Carmen Maniero, Ravi Manikonda, Bobby Mann, Jonathan Manning, Lynne Mannion, Katherine Mansi, Katarina Manso, Dina Mansour, Isheunesu T Mapfunde, Predeesh Mappa, Hemant Maraj, Garikayi Marange, Lisa March, Clare Marchand, Neil Marcus, Maria Marecka, Gomathi Margabanthu, Jordi Margalef, Lavinia 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 McAleese, Helinor McAleese, Paul McAlinden, Audrey McAlpine, Graeme McAlpine, Jonathan McAndrew, Hamish McAuley, Sarah McAuliffe, Claire McBrearty, Carole McBride, Erin McBride, Michael McBuigan, James McBurney, Laura McCabe, Amanda McCairn, Martina McCalmont, Jake McCammon, Nicole McCammon, Conor McCann, Alexandra McCarrick, Brendan McCarron, Eoghan McCarthy, Michelle McCarthy, Natalie McCarthy, Sinead McCaughey, Gareth McChlery, Tara McClay, Beverley McClelland, Declan McClintock, Patricia McCormack, Jacqueline McCormick, Wendy McCormick, Paul McCourt, Jame McCrae, Sharon McCready, Allison McCreath, Gordan McCreath, Helen McCreedy, Louise McCreery, Iain J McCullagh, Josephine McCullagh, Liz McCullagh, Megan McCullagh, Conor McCullough, Katherine McCullough, Nicola McCullough, Sarah McCullough, Fiona McCurrach, Rory McDermott, Katharine McDevitt, Helen McDill, Basil McDonald, Claire McDonald, Debbie McDonald, Rob McDonald, Sam McDonald, Damhnaic McDonald, Rowan McDougall, Irene McEleavy, Julie McEnerney, Julie McEntee, Evanna McEvoy, Ruth McEwen, Margaret McFadden, Denise McFarland, Margaret McFarland, Rachel McFarland, Erin McGarry, Lorcan McGarvey, Margaret McGarvey, Clodagh McGettigan, Michael McGettrick, Christopher McGhee, Fiona McGill, Sarah McGinnity, Hannah McGivern, Neil McGlinchey, Phil McGlone, Deborah McGlynn, Claire McGoldrick, Clare McGoldrick, Elizabeth McGough, Margaret McGovern, Brendan McGrath, Amanda McGregor, Annemarie McGregor, Cathryn McGuinness, Heather McGuinness, Sean McGuire, Tara McHugh, Caroline McInnes, Neil McInnes, Karen McIntyre, Mhairi McIntyre, Carolyn McKay, Lorna McKay, Conor P McKeag, Madeleine McKee, Joseph McKeever, Shirley McKenna, Donogh McKeogh, Denise Mckeown, Caroline McKerr, Anthony M McKie, Claire Mckie, Laura Mckie, Gerard McKnight, Heather McLachlan, Andrew McLaren, Barbara McLaren, Nicola McLarty, Maria McLaughlin, James McLay, Mary McLeish, Tina McLennan, Lorna McLintock, Stewart McLure, Amanda McMahon, Anne Marie McMahon, Genevieve McMahon, Joanne McMahon, Mike McMahon, Stephen McMahon, Terence McManus, Moyra McMaster, Paddy McMaster, Samuel McMeekin, Nicola McMillan, Jason McMinn, Liam McMorrow, Helen McNally, Darren McNamara, Helen Mcnamara, Deborah McNaughton, Fiona McNeela, Lynne McNeil, Claire McNeill, Shea McNeill, Una McNelis, Mary P McNicholl, Melanie McNulty, Roisin McNulty, Christopher McParland, Mark McPhail, Alison McQueen, Anna McSkeane, Denise McSorland, Gini McTaggart, Jacqueline McTaggart, Sam McWilliam, Joanna Mead, Karen Mead, Emma Meadows, Olivia Meakin, Ben Mearns, Claire Mearns, Kim Mears, William Mears, Manjula Meda, Ayren Mediana, Ross Medine, Thomas Medveczky, Sharon Meehan, Matthew Meek, Emily Meeks, Anke Meess, Abbi Megan, Nevan Meghani, Salim Meghjee, Jenny Mehew, Rohan Mehra, Jana Meier, James Meiring, Rayane Mejri, Sabina Melander, Adriana-Stefania Melinte, Stephanie Mellin, Francesca Mellor, Phil Mellor, Samantha Mellor, Zoe Mellor, Katrina Mellows, Vladimir Melnic, Alice Melville, Julie Melville, Helen Membrey, Mark Mencias, Cheryl Mendonca, Alexander Mentzer, Dan Menzies, Sue Mepham, Oliver Mercer, Pauline Mercer, Arwa Merchant, Fatema Merchant, Mihaela Mercioniu, Megan Meredith, Marta Merida Morillas, Blair Merrick, Jack Merritt, Simon Merritt, Ekta Merwaha, Simon Message, Gabriel Metcalf-Cuenca, Benjamin Metcalfe, Kneale Metcalfe, Stella Metherell, Greg Methven, Alexsandra Metryka, Louise Mew, Simon Meyrick, Nhlanhla Mguni, Atiqa Miah, Jagrul Miah, Nahima Miah, Gabriela Mic, Dariush Micallef, Alice Michael, Angiy Michael, Shery Michael, Vincent Michael, Natalia Michalak, Loredana Michalca-Mason, Claire Michelson, Janet Middle, Hayley Middleton, Jennifer T Middleton, Maeve Middleton, Sophie Middleton, Shelley Mieres, Gail Miflin, Loredana Mihalca-Mason, Theresia Mikolasch, Sarah Milgate, Colin Millar, Ian Millar, Jonathan Millar, David Miller, Johnathan Miller, Lucy Miller, Rachel Miller, Naomi Miller-Biot, Alex Miller-Fik, Louise Millett, Hazel Milligan, Iain Milligan, Caitlin Milliken, Katherine Millington, Samuel Millington, Melanie Milloy, Helen Mills, Janet Mills, Steve Mills, Helen Millward, Rebecca Miln, Alice Milne, Charlotte Milne, Louise Milne, Joanne Milner, Zayar Min, Samuel Mindel, Arron Minhas, Chrissie Minnis, Paul Minnis, Anne Minogue, Jane Minton, Frederico Miranda, Lucy Mires, Taimur Mirza, Anjum Misbahuddin, Aseem Mishra, Biswa Mishra, Eleanor Mishra, Ritu Mishra, Sannidhya Misra, Deena Mistry, Heena Mistry, Nita Mistry, Reena Mistry, Dushyant Mital, Sarah Mitchard, Alan Mitchell, Ben Mitchell, Piers Mitchell, Susan Mitchell, Philip Mitchelmore, Andrew Mitra, Atideb Mitra, Sandip Mitra, Clarisse Mizzi, Gloria Mmadubuko, Emma Moakes, Emma Moatt, Gita Modgil, Abdelrahman Mohamed, Arez Mohamed, Osab Mohamed, Waheed Mohammad, Aliabdulla Mohammed, Omer Mohammed, Yaser NS Mohammed, Bilal A Mohamud, Mahalakshmi Mohan, Amr Moharram, Rachel Moir, Jonathan Mok, Christine Moller-Christensen, Mateus Mollet, Malid Molloholli, Aoife Molloy, April Molloy, Linda Molloy, Andrew Molyneux, Tasnim Momoniat, Holly Monaghan, Josephine Monaghan, Krista Monaghan, Shiva Mongolu, Katelyn Monsell, Mahmoud Montasser, Alan Montgomery, Hugh Montgomery, Prebashan Moodley, Ian Moody, Margaret Moody, Nick Moody, Angela Moon, James Moon, Ji-Hye Moon, Maria Moon, May Moonan, Parvez Moondi, Alex Moore, Carly Moore, Christopher Moore, Davidjar Moore, Faye Moore, Gillian Moore, Hannah Moore, Judith Moore, Laura Moore, Sally Moore, Sonia Moore, Tracy Moore, Rachel Moores, Ed Morab, Jose Morales, Nuria Moramorell, Louise Moran, Grishma Moray, Jeronimo Moreno-Cuesta, Adam Morgan, Amy Morgan, Christine Morgan, Colin Morgan, Jackie Morgan, Lauren Morgan, Leila Morgan, Matthew Morgan, Patrick Morgan, Katie Morgan-Jones, Emily Morgan-Smith, Anna Morley, Thomas Morley, Wendy Morley, Anna Morris, Damian Morris, Fiona Morris, Helen Morris, Juliet Morris, Katie Morris, Laura Morris, Lucy Morris, Mary-Anne Morris, Niall Morris, Paul Morris, Sheila Morris, Susan Morris, Douglas Morrison, Moira Morrison, Mary Morrissey, Anna Morrow, Chantal Morrrell, Franca Morselli, Gordon Mortem, Chelsea Morton, Gordon Morton, Rosna Mortuza, Priti Morzaria, Alison Moss, Charlotte Moss, Rachel Moss, Sarah Moss, Stuart Moss, Nicki Motherwell, Johanna Mouland, Caroline Moulds, Hilary Moulton, Lorraine Mounsey, Elizabeth Mousley, Karen Moxham, Borja Moya, Quberkani Moyo, Eunice Mshengu, Sheila Mtuwa, Ali Muazzam, Iqtedar A Muazzam, Nykki Muchenje, Dalia Mudawi, Girish Muddegowda, Imran Mugal, Ahsan Mughal, Javaid Muglu, Javed Muhammad, Alison Muir, Carol Muir, Martin Muir, Dipak Mukherjee, Syed Asim Ali Mukhtar, Denise Mukimbiri, Tshinupay Mukwa, Peter Mulgrew, Ben Mulhearn, Arafat Mulla, Dee Mullan, Dileepkumar Mullasseril Kutten, Niall Mullen, Rosemary Mullett, Sandra Mulligan, Barbara Mullin, Joanne Mullings, Lana Mumelj, Andrew Mumford, Sarah Mumford, Mohammed Munavvar, Henry Munby, Anne-Marie Munro, Sheila Munt, Nafissah Munu, McDonald Mupudzi, Arshid Murad, Oluwatosin H Muraina, Koteshwara Muralidhara, Diane Murdoch, Mhairi Murdoch, Jennifer Murira, Alison Murphy, Carl Murphy, Emily Murphy, Fidelma Murphy, Gail Murphy, Jo Murphy, Peter Murphy, Sheenagh Murphy, Simon Murphy, Clare Murray, David Murray, Eleanor Murray, Katie Murray, Kenneth Murray, Lisa Murray, Lorna Murray, Tracey Murray, Eoin Murtagh, Mithun Murthy, Catherine Murton, Rosie Murton, Neeka Muru, Rosemary Musanhu, Maimuna Mushabe, Kaiser Mushtaq, Omaisa Mushtaq, Ahmed M Mustafa, Elhaytham Mustafa, Mustafa Mustafa, Ibrahim Mustapha, Zhain Mustufvi, Callum Mutch, Eric Mutema, Balakumar Muthukrishnan, Sheree Mutton, Natasha Muzengi, Memory Mwadeyi, Bettina Mwale, Esther Mwaura, Raji Myagerimath, Alice Myers, Sam Myers, Khin Swe Myint, Yadee Myint, Libor Myslivecek, Helen Nabakka, Evelyn Nadar, Iftikhar Nadeem, Moosa Nadheem, Asma Naeem, Hassan Naeem, Salman Naeem, Samraiz Nafees, Mohamed Nafei, Parminder Naga, Thapas 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 E Neils, Avideah Nejad, Louise Nel, Marie Nelson, Richard Nelson, Scott Nelson, Rajesh Nemane, Samiksha Nepal, Daniel Nethercott, Kimberley Netherton, Kimberley Nettleton, Claire-Michelle Neville, Tracy Nevin, Josephine Newanji, Alison Newby, Angela Newby, David Newby, Tracy Newcombe, Charlotte Newman, Diana Newman, Julie Newman, Oscar Newman, Richard Newman, Tabitha Newman, Thomas Newman, Rachel Newport, Claire Newsam, Christopher Newson, Maria Newton, Anthony YKC Ng, Ka Wing Ng, Maxine Ng, Sarah Ng, Wee Jin Ng, Thomas Ngan, Gabriel CE Ngui, Alice Ngumo, Caoimhe Nic Fhogartaigh, Nathalie Nicholas, Philip Nicholas, Rachel Nicholas, Teresa Nicholas, Donna Nicholls, Lisa Nicholls, Alice Nicholson, Anne Nicholson, Annette Nicholson, Janet Nicholson, Ian Nickson, Eileen Nicol, Elizabeth Nicol, Rebecca Nicol, Pantelis Nicola, Antony Nicoll, Pantzaris Nikolaos, Georgii Nikonovich, Annette Nilsson, Kofi Nimako, Louise Nimako, Camus Nimmo, Preethy Ninan, Mahesh Nirmalan, Muhammad Nisar, Toby Nisbett, Aksinya Nisha James, Sabaahat Nishat, Tomoko Nishiyama, Sara Nix, Jennifer Nixon, Maxine Nixon, Khwaja Nizam Ud Din, Maria Nizami, Josephine Nnadi, Lyrics Noba, Harriet Noble, Hsu Noe, Jerry Nolan, Zahid Noor, Zaid Noori, Jamie Norgrave, Louis Norman, Rachel Norman, Karen Norris, Lillian Norris, Sally Ann Nortcliffe, Fiona North, Julie North, Thomas North, Julie Northcote, John Northfield, Samantha Northover, Jurgens Nortje, Donna Norton, Rowen Norton, Holly Notman, Khalid Nourein, Timea Novak, Tony Noyce, Alan Noyon, Arlene Nubi, Mohamed Nugdallah, Anne Marie Nugent, Justine Nugent, Kribashnie Nundlall, Kieran Nunn, Michelle Nunn, Jane Nunnick, Yvonne Nupa, Zubeir Nurgat, Kelly Nwankiti, Eugenia Nweje, Godfrey Nyamugunduru, Maggie Nyirenda, Kerry Nyland, Daire O Shea, Ruth O'Donnell, Chloe O'Hara, Kevin O'Reilly, William O'Rourke, Caroline Oakley, Begho Obale, Clements Oboh, Andrew O'Brien, Clare O'Brien, Julie O'Brien, Kirsty O'Brien, Linda O'Brien, Marese O'Brien, Neale O'Brien, Rachel O'Brien, Sarah O'Brien, Tracey O'Brien, Emma O'Bryan, Ross Obukofe, Christopher O'Callaghan, Lorcan O'Connell, Maria O'Connell, Tadg OConnor, Chris O'Connor, Grainne O'Connor, Miranda Odam, Sam Oddie, Sharon Oddy, Rosie O'Dea, Yejide Odedina, Krishma Odedra, Sven W Odelberg, Natasha Odell, Omolola Oderinde, Jessica Odone, Catherine O'Donovan, Dapo Odumeru, Stephen O'Farrell, Pamela Offord, Tanwa Ogbara, Catherine Ogilvie, Ciaran O'Gorman, Oluwatomilola Ogunkeye, Udeme Ohia, Shinjali Ohja, Ohiowele Ojo, Mark O'Kane, Tolu Okeke, Eleanor OKell, Alicia Okines, Iheoma Okpala, Ernest Okpo, Maryanne Okubanjo, Ché Okyne-Turkson, Raphael Olaiya, Tim Old, Jane Oldham, Gregory Oleszkiewicz, Marta Oliveira, Annie Oliver, Catherine Oliver, Jesse Oliver, Martyn Oliver, Zoe Oliver, Nurudeen O Olokoto, Folusho Olonipile, Olumide Olufuwa, Olatomiwa Olukoya, Akinlolu Oluwole-Ojo, Laura O'Malley, Maryam Omar, Zohra Omar, Nimca Omer, Abi Omojola, Helen Omuco, Bronagh O'Neill, Connaire O'Neill, Lauran O'Neill, Chon Sum Ong, Chidera Onyeagor, Huah C Ooi, Amin Oomatia, Maria Opena, Richard Oram, Chloe Orchard, Christy Ord, Jonathan Ord, Charlotte O'Reilly, Lola Orekoya, Devaki O'Riordan, Sean O'Riordan, Amy Orme, Hannah Orme, Dave Ormrod, Charlotte Orr, Sarah Orr, Christopher Orton, Anna Osadcow, Rawlings Osagie, Rostam Osanlou, Lynn Osborne, Nigel Osborne, Rebecca Osborne, Wendy Osborne, William Osborne, Charles Osbourne, Jennifer Osei-Bobie, Mandy O'Shea, Joseph Osman, Wa'el Osman, Bashir Osman, G Osoata, Marlies Ostermann, Eoin O'Sullivan, Susan O'Sullivan, Noor Otey, Otheroro K. Otite, Marie O'Toole, Natalie Outten, Rachel Owen, Stephanie Owen, Emma Owens, Susan Owens, Yetunde Owoseni, Michael Owston, Ruth Oxlade, Feray Ozdes, Jamie Pack, Sophie Packham, Piotr Paczko, Grace Padden, Anand Padmakumar, Iain Page, Nickolas Page, Valerie Page, Jodi Paget, Katherine Pagett, Lee Paisley, Susie Pajak, Angela Pakozdi, Soubhik Pal, Sushi Pal, April Palacios, Vishnu B Palagiri Sai, Vadivu Palaniappan, Priya Palanivelu, Adrian Palfreeman, Shehan Palihavadana, Deepshikha Palit, Alistair Palmer, Lorna Palmer, Lynne Palmer, Ian Pamphlett, Anmol Pandey, Nithya Pandian, Krishnaa Pandya, Tej Pandya, Alice Panes, Yee Wei Pang, Laura Pannell, Kanwar Pannu, Sathianathan Panthakalam, Charles T Pantin, Norman Pao, Helen Papaconstantinou, Padmasayee Papineni, Marina Pappa, Kitty Paques, Kerry Paradowski, Vinay Parambil, Supathum Paranamana, Siddhant Parashar, Ian Parberry, Ana Parejasanchez, Amy Parekh, Dhruv Parekh, Louise Parfitt, Helen Parfrey, Omi Parikh, Gemma Parish, John Park, 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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, 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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 Samakomva, Renaldo Samlal, Emily Sammons, David Sammut, Mark Sammut, Zoe Sammut, Sunitha Sampath, Claire Sampson, Julia Sampson, Aashna Samson, Anda Samson, Johnson Samuel, Lorraine Samuel, Merna Samuel, Reena Samuel, Thomas DL Samuel, Younan Samuel, Elsward Samuels, Theo Samuels, Joanna Samways, Manjula Samyraju, Francisco San Diego, Ilves Sana, Veronica Sanchez, Amada Sanchez Gonzalez, Alina Sanda-Gomez, Paul Sandajam, Peter Sandercock, Amy Sanderson, Colleen Sanderson, Tom Sanderson, Kuljinder Sandhu, Loveleen Sandhu, Sam Sandow, Victoria Sandrey, Sarah Sands, Mirriam Sangombe, Mathew Sanju, Filipa Santos, Rojy Santosh, Jayanta Sanyal, Aureo F Sanz-Cepero, Dinesh Saralaya, Arun Saraswatula, Joshua Sarella, Avishay Sarfatti, Rebecca Sargent, Beatrix Sari, Khatija Sarkar, Rahuldeb Sarkar, Sruthi Sarma, Zainab Sarwar, Thea Sass, Sonia Sathe, Sobitha Sathianandan, Abilash Sathyanarayanan, Lavanya SJP Sathyanarayanan, Thozhukat Sathyapalan, Prakash Satodia, Vera Saulite, Andrew Saunders, 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. Scott, Alistair Scott, Anne Scott, Catherine Scott, Christine Scott, Emily Scott, Graham Scott, Kathyn Scott, Leanne Scott, Martha Scott, Michelle Scott, Stephen Scott, Timothy Scott, Sarah Scourfield, Wendy Scrase, Angela Scullion, Therese Scullion, Richard Seabury, Emily Seager, Cathy Seagrave, Deborah Seals, Rebecca Seaman, Eleanor Sear, Isabella Seaton, Anna Seckington, Joanna Sedano, Deborah Seddon, Gabrielle Seddon, Muhammad A Seelarbokus, Christopher Sefton, Matias Segovia, Fatima Seidu, Gillian Sekadde, Mallika Sekhar, Faye Selby, Georgina Selby, Jo Sell, Claire Sellar, Katharine Sellers, Joseph Selley, Victoria Sellick, Gobika Selvadurai, Brintha Selvarajah, Haresh Selvaskandan, Subothini S Selvendran, Gary Semple, Nandini Sen, Seema Sen, Aditya Sengupta, Niladri Sengupta, Helen Senior, Peter Senior, Susana Senra, HoJan Senya, Niranjan Setty, Abigail Seward, Teswaree Sewdin, Jack Seymour, Hussam Shabbir, Tracey Shackleton, Fiona Shackley, Tariq Shafi, Aashni Shah, Ahmar Shah, 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 Tahir, Muhammad Tahir, Silvia Taibo, Zsofia Takats, Abigail Takyi, Peter Talbot, Alison Talbot -Smith, James Talbot-Ponsonby, Richard Tallent, Bradley Tallon, Phoebe Tamblin-Hopper, Adrian Tan, Bee T Tan, Hock Tan, Huey Tan, Jade Tan, Keith Tan, WeiTeen Tan, Anand Tana, Xiaohui Tang, Christina Tanney, Tabitha Tanqueray, Emma Tanton, Ran Tao, Mark Taplin, Hayley Tarft, Priyal Taribagil, Obaid Tarin, Syed Tariq, Zeeshan Tariq, David Tarpey, Lisa Tarrant, Antonia Tasiou, Elizabeth Tatam, Margaret L Tate, Kate Tatham, Vera Tavoukjian, Alexander Taylor, Beverley Taylor, Brian Taylor, Charlie Taylor, Charlotte Taylor, David Taylor, Elisabeth Taylor, Janet Taylor, Jennifer Taylor, Joanne Taylor, Julie Taylor, Karen Taylor, Leanne Taylor, Margaret Taylor, Matthew Taylor, Melanie Taylor, Natalie Taylor, Rachael Taylor, Rachel Taylor, Samantha Taylor, Suzanne Taylor, Tina Taylor, Tracey Taylor, Vicky Taylor, Michelle Taylor-Siddons, Thomas Taynton, Amelia Te, Jessica Teasdale, Julie Tebbutt, 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

26. An epitope-based approach of HLA-matched platelets for transfusion: a noninferiority crossover randomized trial

Author: Delordson Kallon, Judith C. W. Marsh, Cristina Navarrete, Laura Pankhurst, Ana Mora, Ghulam J. Mufti, Deborah Sage, Renate Hodge, Collette Pigden, Charlotte Llewelyn, Emma Laing, Kay Harding, Joanne Brown, Louise L. Choo, Simon J. Stanworth, Adeline Z. Gilbertson, Aleksandar Mijovic, Alison J Deary, and Colin J. Brown
Subjects: Adult, Blood Platelets, Male, medicine.medical_specialty, Adolescent, Immunology, Platelet Transfusion, 030204 cardiovascular system & hematology, Biochemistry, law.invention, Epitopes, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Antibody Specificity, HLA Antigens, law, Internal medicine, medicine, Humans, Amino Acid Sequence, Aplastic anemia, Aged, Cross-Over Studies, Intention-to-treat analysis, business.industry, Histocompatibility Testing, Transfusion medicine, Cell Biology, Hematology, Middle Aged, medicine.disease, Crossover study, Confidence interval, Platelet transfusion refractoriness, Treatment Outcome, Conventional PCI, Female, business, 030215 immunology
Abstract: Platelet transfusion refractoriness results in adverse outcomes and increased health care costs. Managing refractoriness resulting from HLA alloimmunization necessitates the use of HLA antigen–matched platelets but requires a large platelet donor pool and does not guarantee full matching. We report the first randomized, double-blind, noninferiority, crossover trial comparing HLA epitope–matched (HEM) platelets with HLA standard antigen–matched (HSM) platelet transfusions. Alloimmunized, platelet-refractory, thrombocytopenic patients with aplastic anemia, myelodysplastic syndrome, or acute myeloid leukemia were eligible. HEM platelets were selected using HLAMatchMaker epitope (specifically eplet) matching. Patients received up to 8 prophylactic HEM and HSM transfusions provided in random order. The primary outcome was 1-hour posttransfusion platelet count increment (PCI). Forty-nine patients were randomized at 14 UK hospitals. For intention to treat, numbers of evaluable transfusions were 107 and 112 for HEM and HSM methods, respectively. Unadjusted mean PCIs for HEM and HSM methods were 23.9 (standard deviation [SD], 15) and 23.5 (SD, 14.1), respectively (adjusted mean difference, −0.1; 95% confidence interval [CI], −2.9 to 2.8). Because the lower limit of the 95% CI was not greater than the predefined noninferiority limit, the HEM approach was declared noninferior to the HSM approach. There were no differences in secondary outcomes of platelet counts, transfusion requirements, and bleeding events. Adequate 1-hour PCI was more frequently observed, with a mean number of 3.2 epitope mismatches, compared with 5.5 epitope mismatches for inadequate 1-hour increments. For every additional epitope mismatch, the likelihood of an adequate PCI decreased by 15%. Epitope-matched platelets should be considered to support HLA alloimmunized patients. This trial was registered at www.isrctn.com as #ISRCTN23996532.
Published: 2021

27. Benchmarking causal reasoning algorithms for gene expression-based compound mechanism of action analysis

Author: Layla Hosseini-Gerami, David A. Collier, Emma Laing, David Evans, Howard Broughton, and Andreas Bender
Abstract: Background Elucidating compound mechanism of action (MoA) is beneficial to drug discovery, but in practice often represents a significant challenge. Causal Reasoning approaches aim to address this situation by inferring dysregulated signalling proteins using transcriptomics data and biological networks; however, a comprehensive benchmarking of such approaches has not yet been reported. Here we benchmarked four causal reasoning algorithms (SigNet, CausalR, CausalR ScanR and CARNIVAL) with four networks (the smaller Omnipath network vs. 3 larger MetaBase™ networks), using LINCS L1000 and CMap microarray data, and assessed to what extent each factor dictated the successful recovery of direct targets and compound-associated signalling pathways in a benchmark dataset comprising 269 compounds. We additionally examined impact on performance in terms of the functions and roles of protein targets and their connectivity bias in the prior knowledge networks. Results According to ANOVA analysis, the combination of algorithm and network most significantly dictated the performance of causal reasoning algorithms, with the SigNet recovering the greatest number of direct targets. With respect to the recovery of signalling pathways, CARNIVAL with the Omnipath network was able to recover the most informative pathways containing compound targets, based on the Reactome pathway hierarchy. We found no significant difference in performance between L1000 data or microarray data, even when limited to just 978 ‘landmark’ genes. Notably, all causal reasoning algorithms also outperformed pathway recovery based on input DEGs, despite these often being used for pathway enrichment. Causal reasoning methods performance was somewhat correlated with connectivity and biological role of the targets. Conclusions Overall, we conclude that causal reasoning performs well at recovering compound MoA upstream from gene expression changes by leveraging prior knowledge networks, and that the choice of network and algorithm has a profound impact on the performance of causal reasoning algorithms. Based on the analyses presented here this is true for both microarray-based gene expression data as well as those based on the L1000 platform.
Published: 2022

28. Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author: Erin Murphy, Franca Danielle, Carlos Cabello-Gutierrez, Jason A. Roberts, Juan-Manuel Anaya, Fabio Saccona, Paula A. Gaviria García, Geert Meyfroidt, Olufemi Erinoso, Joshua S. Davis, Oskar Ljungquist, Rossana Cavallo, Kathryn M Rowan, James S. Molton, Alberto Romero, Gitana Scozzari, Alexander V. Ivanov, Manaf AlQahtani, Eduardo Rego, Luis E. Argumanis, Jeffrey H. Jennings, German Jr J. Castillo, Deonne Thaddeus V. Gauiran, M. Rahman, Anne Françoise Donneau, Josephine Anne C. Lucero, Christian J. Fareli, Fresthel Monica M. Climacosa, Adrián Camacho-Ortiz, Aditya Kotecha, Nadia Birocco, Damon H. Cao, David Price, Joe Sasadeusz, Jose M. Ignacio, Antonella Cingolani, Abdulkarim Abdulrahman, Alisa Higgins, Perrine Janiaud, James Daly, Eduardo Perez-Alba, Henrik Nielsen, Cecile C. Dungog, Paul Klenerman, Fazle Rabbi Chowdhury, Diana M. Monsalve, Claudia M. Denkinger, Andreas M. Schmitt, Lyn Li Lim, Heli Harvala, Mahesh C. Patel, Alexis F. Turgeon, Akin Abayomi, Vladimir P. Baklaushev, Rachelle N. Alfonso, Fiorella Krapp, Juan E. Gallo, Januario D. Veloso, Lynn B. Bonifacio, Bryan J. McVerry, Mehdi Safdarian, Ismael F. Aomar, Yanet Ventura-Enriquez, Alric V. Mondragon, Pedrito Y. Tagayuna, Mona Landin-Olsson, Yhojan Rodríguez, Nina Khanna, André Gothot, David Grimaldi, Forhad Hossain Chowdhury, Paola M. Manzini, Farah Al-Beidh, Vivekanand Jha, Ángel Augusto Pérez-Calatayud, Inmaculada Poyato, Salvador Oyonarte, Anne Kristine H. Quero, Manuel Rojas, Carlo Francisco N. Cortez, Bernardo Camacho, Elvira Garza-González, Susan C. Morpeth, Steve Webb, Anastasia Perkina, Marissa M. Alejandria, Emma Laing, Matthew V. N. O'Sullivan, Naomi Perry, Karin Holm, Alexander Averyanov, John P. A. Ioannidis, Mutien Garigliany, Patricia J. Garcia, Ashraful Hoque, Ivy Mae S. Escasa, Jodor Lim, Paul R. Mouncey, Balasubramanian Venkatesh, Kai Zacharowski, Lise J Estcourt, Concepción López-Robles, Teresita E. Dumagay, Megan Rees, Emily R. Smith, Juan C. Díaz-Coronado, Jorge M. Llaca-Díaz, Julián Olalla, Janneke van 't Hooft, S. Rahman, Michel Moutschen, Pierre-François Laterre, Carlos A. Peña-Perez, Geneva Tatem, Mandana Pouladzadeh, Sandy C. Maganito, Lars G. Hemkens, Benjamin A. Rogers, Ryan Zarychanski, Mark Angelo C. Ang, Amy Evans, Susanna Dunachie, Tom Snelling, Claudia Galassi, Anthony C. Gordon, Ana Cardesa, Jesus A. Garcia, Colin McArthur, Akin Osibogun, Zoe McQuilten, David Moher, Juan Mauricio Pardo-Oviedo, Benoît Misset, Naomi E Hammond, Maria Clariza M. Santos, Maria Lundgren, Yeny Acosta-Ampudia, Steven Y. C. Tong, Ana M. Mata, Gorav Sharma, Sergio D’Antico, Maike Janssen, Alistair Nichol, Christian Wikén, Noah Haber, Alaa AlZamrooni, Alonso Soto, Jens Kjeldsen-Kragh, Salvador López-Cárdenas, Patricia L. Garcia, Manu Shankar-Hari, Rubén D. Manrique, Ileana Lopez-Plaza, Sally Campbell-Lee, Giovannino Ciccone, Jeser Santiago Grass Guaqueta, Miguel Marcos, Francisco M. Heralde, Richard M. Novak, Eric Hoste, Asha C. Bowen, Ignacio Marquez, Abel Costa Neto, David K. Menon, Ma Angelina L. Mirasol, Magnus Rasmussen, David Gómez-Almaguer, Erica M. Wood, Jennifer Hines, Daniel Desmecht, Olga Balionis, Thomas Benfield, Veronica Fernandez-Sanchez, Ruby Anne N King, Jesús Rodríguez-Baño, David L. Paterson, Jose M. Carnate, Carolina Ramírez-Santana, Lothar Wiese, Luciana Labanca, Cameron Green, Jose Antonio Giron-Gonzalez, Abbie Bown, Scott Berry, Agnes L.M. Evasan, Juan A. Díaz Ponce-Medrano, Manal Abduljalil, Anna Flor G. Malundo, Justin T Denholm, Amy Tang, Juan Macías, Luciana Teofili, Veerle Compernolle, Steven N. Goodman, Manuela Aguilar-Guisado, Thomas Hills, Cathrine Axfors, Tome Najdovski, Jesica A. Herrick, Bodunrin Osikomaiya, David J. Roberts, Mayur Ramesh, Francesco Giuseppe De Rosa, Francisco Javier Martínez-Marcos, Mohammed K. Ali, Gaukhar M. Yusubalieva, Carsten Müller-Tidow, Parastoo Moradi Choghakabodi, AlQahtani, Manaf [0000-0002-1523-0429], Hills, Thomas E [0000-0003-0322-5822], Hoste, Eric [0000-0001-9301-8055], Price, David J [0000-0003-0076-3123], Yusubalieva, Gaukhar M [0000-0003-3056-4889], Apollo - University of Cambridge Repository, University of Manitoba, NIHR, National Institute for Health Research, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, and UCL - (SLuc) Service de soins intensifs
Subjects: medicine.medical_specialty, Infectious Medicine, Convalescent plasma, Infektionsmedicin, Infectious and parasitic diseases, RC109-216, 030204 cardiovascular system & hematology, Passive, Placebo, Microbiology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, 1108 Medical Microbiology, law, Internal medicine, Medicine and Health Sciences, Medicine, Humans, 030212 general & internal medicine, COVID-19 Serotherapy, Randomized Controlled Trials as Topic, Science & Technology, business.industry, SARS-CoV-2, Immunization, Passive, COVID-19, 1103 Clinical Sciences, Intensive care unit, Confidence interval, 3. Good health, TIME, Clinical trial, Settore MED/15 - MALATTIE DEL SANGUE, Meta-analysis, Clinical research, Treatment Outcome, Infectious Diseases, Relative risk, Immunization, business, Life Sciences & Biomedicine, Research Article, 0605 Microbiology, COVID-19/therapy
Abstract: This collaborative meta-analysis was supported by the Swiss National Science Foundation and the Laura and John Arnold Foundation (grant supporting the post-doctoral fellowship at the Meta-Research Innovation Center at Stanford (METRICS), Stanford University). The funders had no role in the design of this collaborative meta-analysis; in the collection, analysis, and interpretation of data; or in the report writing., We would like to express our warm gratitude to all participating patients and convalescent plasma donors. We thank Katja Suter and Sina Ullrich, University of Basel, for their administrative assistance. For their helpful contribution to individual trials, we thank Erica Wood, Iain Gosbell, Richard Charlewood, Thomas Hills, Veronica Hoad, Kristina Kairaitis, Aikaj Jindal, John Gerrard, Hong Foo, Adam Stewart, and Nanette Trask (ASCOT trial); Amalia Bravo-Lindoro, Ral Carrillo-Esper, Karla Maldonado-Silva, Catalina Casillas-Suárez, Orlando Carrillo-Torres, Sandra Murrieta, Elizabeth Diaz-Padilla, Eli Omar Zavaleta, Yadira Bejar-Ramirez, and Evelyn Cortina-de la Rosa (CPC-SARS trial); Sheri Renaud, Roel Rolando-Almario, and Jacqueline Day (NCT04385199 trial); Sandra Tingsgrd, MD, Karen Brorup Heje Pedersen, MD, Michaela Tinggaard, MD, Louise Thorlacius-Ussing, MD, Clara Lundetoft Clausen, MD, Nichlas Hovmand, MD, Simone Bastrup Israelsen, MD, Cecilie Leding, MD, Katrine Iversen, MD, Maria Engel Miller, MD, Hkon Sandholdt, MSc biostatistician (CCAP-2 trial). On behalf of the IRCT20200310046736N1 trial, we thank the Khuzestan Blood Transfusion Organization for specialized assistance in the preparation and maintenance of plasma samples. On behalf of the NCT04332835 trial, we thank all the members of the "PC-COVID-19 Group" at the Clinica del Occidente and Hospital Universitario Mayor Mederi in Bogota, and Clinica CES in Medellin. On behalf of the NCT04403477 trial, we thank Miles Carroll for his support regarding the antibody testing in Bangladesh. The Co-CLARITY team would like to extend their gratitude to the Department of Science and Technology Philippine Council for Health Research and Development and the UP-Philippine General Hospital for all their support in the setting up and conduct of the trial. For helpfully communicating details of their trial, we thank members of the PlasmAr trial, NCT04359810 trial (Max O´Donnell), NCT04468009 trial, and CTRI/2020/05/025299 trial. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute (https://www.cancer.gov/)., During the conduct of the study, the following is reported: Dr. Berry reports being employee with ownership role at Berry Consultants (receives payments for statistical modeling and design of REMAP-CAP). Dr. Castillo reports grants from DOST PCHRD. Dr. Daly reports grants from Medical Research Future Fund (Australian Govt) and RBWH. Dr. Denkinger reports grants from German Ministry for Education and Research. Dr. Dumagay reports grants from Philippine Council for Health Research and Development. Dr. Dunachie reports grants from UK Department of Health and Social Care, grants from UK National Institute of Health Research. Dr. Gauiran reports grants from Department of Science and Technology—Philippine Council for Health Research and Development. Dr. Gordon reports grants from NIHR, grants from NIHR Research Professorship (RP-2015-06-18), and non-financial support from NIHR Clinical Research Network. Dr. Higgins reports grants from NHMRC and from the Minderoo Foundation. Dr. Hills reports grants from Health Research Council of New Zealand. Dr. Holm reports grants from Swedish Government Funds for Clinical Research (ALF). Dr. Janssen and Dr. Müller-Tidow report grants from the Federal Ministry of Education and Research in Germany (BMBF) to the RECOVER clinical trial. Dr. Krapp reports grants from Department of Foreign Affairs, Trade, and Development of Canada, grants from Fundación Telefónica del Perú. Dr. J. Lim reports grants from the Department of Science and Technology, Philippine Council for Health Research and Development. Dr. Lucero reports grants from Philippine Council for Health Research and Development. Dr Manrique reports economic support from Grupo ISA Intercolombia for the project development of trial NCT04332835. Drs. McQuilten and Wood report grants from Medical Research Future Fund. Dr. McVerry reports grants from The Pittsburgh Foundation, Translational Breast Cancer Research Consortium, and from UPMC Learning While Doing Program. Mr. Mouncey reports grants from National Institute for Health Research and from the European Union FP7: PREPARE. Dr. Najdovski reports payment from KUL Leuven to Belgian Red Cross for supply of convalescent plasma. Dr. Nichol reports grants from Health Research Board of Ireland. Dr. D. Roberts reports grants from the National Institute for Health (UKRIDHSC COVID-19 Rapid Response Rolling Call—Grant Reference Number COV19-RECPLAS) and the European Commission (SUPPORT-E #101015756). Dr. Rowan reports grants from the European Commission and from the UK National Institute for Health Research. Dr. Shankar-Hari reports grants from National Institute for Health Research UK, grants from UKRI-National Institute for Health Research UK. Dr. Turgeon reports grants from Canadian Institutes of Health Research. Dr. Venkatesh reports grants from Baxter. Dr. Webb reports grants from National Health and Medical Research Council, grants from Minderoo Foundation. Dr. Zacharowski reports grants from EU Horizon 2020. The ASCOT trial team (Drs Bowen, Daly, Davis, Denholm, Hammond, Jha, L. Lim, McQuilten, Molton, Morpeth, O’Sullivan, Paterson, Perry, Price, Rees, Roberts, Rogers, Sasadeusz, Snelling, Tong, Venkatesh, Wood) is funded by grants from from Royal Brisbane and Women’s Hospital Foundation, Pratt Foundation, Minderoo Foundation, BHP Foundation, Hospital Research Foundation, Macquarie Group Foundation, Health Research Council of New Zealand, Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE), and the collection and supply of convalescent plasma was conducted within Lifeblood’s funding arrangements. The CONFIDENT trial is funded by the Belgian KCE (blood establishments received payment for the convalescent plasma supplied in the clinical trial). REMAP-CAP was supported in part by funding from UKRIDHSC COVID-19 Rapid Response Rolling Call (Grant Reference Number COV19-RECPLAS). Collection of convalescent plasma for REMAP-CAP was funded by the Department of Health and Social Care, UK. The IRCT20200310046736N1 trial was supported by the Ahvaz Jundishapur University of Medical Sciences (Grant No. R.AJUMS.REC.1399.003, Dr. Pouladzadeh). The PC-COVID-19 Group is supported by the Universidad del Rosario, IDCBIS, ISA Group and Suramericana (Colombia). Outside the submitted work, the following is reported: Dr. Axfors reports postdoctoral grants from the Knut and Alice Wallenberg Foundation, Uppsala University, the Swedish Society of Medicine, the Blanceflor Foundation, and the Sweden-America Foundation. Dr. Aomar reports personal fees from SOBI, GEDEON RICHTER, and GSK. Dr. Benfield reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Hansen Foundation, Erik and Susanna Olesen’s Charitable Fund; grants and personal fees from GSK, Pfizer, Gilead; and personal fees from Boehringer Ingelheim, MSD, and Pentabase ApS. Dr. Estcourt reports being an investigator on the RECOVERY trial. Dr. Gordon reports personal fees from GlaxoSmithKline, Bristol Myers Squibb, and 30 Respiratory. Dr. Jha reports grants and personal fees from Baxter Healthcare, personal fees from Astra Zeneca, grants from NephroPlus. Dr. Laterre reports personal fees from Adrenomed. Dr. McVerry reports grants from NIH/NHLBI and Bayer Pharmaceuticals, Inc. Dr. Mondragon reports financial activities outside the submitted work (employment at Johnson & Johnson). Dr. Perry reports partner being employed at CSL and owning shares in CSL. Dr. Paterson reports involvement with ALLIANCE trial of COVID-19 treatments. Dr. J. Roberts reports other COVID-19 related trials (in different patient groups): tocilizumab in ICU patients; hydroxychloroquine dosing in ICU patients; planned study of remdesivir pharmacokinetics in patients during expanded access program; and in silico evaluation of ivermectin dosing. Dr Sasadeusz reports grants from various Pharma companies including Gilead Sciences, Abvvie, Merck, and Takeda. Dr. Zacharowski reports personal fees from Biotest AG, CSL Behring, GE Heathcare, and is President of the ESAIC., Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care., Amalia Bravo-Lindoro, BHP Foundation, Blanceflor Foundation, Department of Foreign Affairs, Trade, and Development of Canada, Eli Omar Zavaleta, Erik and Susanna Olesen’s Charitable Fund, Federal Ministry of Education and Research in Germany, Fundación Telefónica del Perú, IDCBIS, ISA Group and Suramericana, Kai Hansen Foundation, Katja Suter and Sina Ullrich, Khuzestan Blood Transfusion Organization, Macquarie Group Foundation, Medical Research Future Fund, NephroPlus, RBWH, Roel Rolando-Almario NCT04385199, Royal Brisbane, Sheri Renaud, Simonsen Foundation, UKRI-National Institute for Health Research UK, UKRIDHSC COV19-RECPLAS, UP-Philippine General Hospital CTRI/2020/05/025299, NCT04359810, NCT04468009, Women’s Hospital Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, Pittsburgh Foundation, Pfizer, Baxter International, Stanford University, Gilead Sciences, National Institute on Handicapped Research RP-2015-06-18, Meso Scale Diagnostics, Universität Basel, Laura and John Arnold Foundation, Health Research Board, Pratt Foundation, Canadian Institutes of Health Research, National Institute for Health Research, Department of Health and Social Care, European Commission 101015756, National Health and Medical Research Council, Department of Science and Technology, Ministry of Science and Technology, India, Health Research Council of New Zealand, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Sweden-America Foundation, Bundesministerium für Bildung und Forschung, Lundbeckfonden, Knut och Alice Wallenbergs Stiftelse, Seventh Framework Programme, Ahvaz Jundishapur University of Medical Sciences, Université Pierre et Marie Curie, Uppsala Universitet, Horizon 2020, Svenska Läkaresällskapet, Universidad del Rosario, Pharmaceuticals Bayer, Novo Nordisk Fonden, Department of Science and Technology, Philippines, Philippine Council for Health Research and Development, Minderoo Foundation
Published: 2021

29. Highly-Sensitive Lineage Discrimination of SARS-CoV-2 Variants through Allele-Specific Probe Polymerase Chain Reaction

Author: A Jennings, David Bonsall, Paul R Mouncey, Peter Simmonds, Heli Harvala, Farah Al-Beidh, C Jay, S Bibi, M N Ramasamy, S A Costa Clemens, David J. Roberts, D Nguyen, Kathy Rowan, J Rynne, Teresa Lambe, G MacIntyre-Cockett, Tanya Golubchik, P M Folegatti, M Fish, Jeremy Ratcliff, M Shankar-Hari, Lise J Estcourt, David K. Menon, Anthony C. Gordon, Andrew J. Pollard, Amy Evans, Sarah Williams, and Emma Laing
Subjects: Oligonucleotide, law, Lineage (evolution), Single-nucleotide polymorphism, Gold standard (test), Computational biology, Primer (molecular biology), Viral load, Polymerase chain reaction, Virus, law.invention
Abstract: IntroductionTools to detect SARS-Coronavirus-2 variants of concern and track the ongoing evolution of the virus are necessary to support public health efforts and the design and evaluation of novel COVID-19 therapeutics and vaccines. Although next-generation sequencing (NGS) has been adopted as the gold standard method for discriminating SARS-CoV-2 lineages, alternative methods may be required when processing samples with low viral loads or low RNA quality.MethodsAn allele-specific probe polymerase chain reaction (ASP-PCR) targeting lineage-specific single nucleotide polymorphisms (SNPs) was developed and used to screen 1,082 samples from two clinical trials in the United Kingdom and Brazil. Probit regression models were developed to compare ASP-PCR performance against 1,771 NGS results for the same cohorts.ResultsIndividual SNPs were shown to readily identify specific variants of concern. ASP-PCR was shown to discriminate SARS-CoV-2 lineages with a higher likelihood than NGS over a wide range of viral loads. Comparative advantage for ASP-PCR over NGS was most pronounced in samples with Ct values between 26-30 and in samples that showed evidence of degradation. Results for samples screened by ASP-PCR and NGS showed 99% concordant results.DiscussionASP-PCR is well-suited to augment but not replace NGS. The method can differentiate SARS-COV-2 lineages with high accuracy and would be best deployed to screen samples with lower viral loads or that may suffer from degradation. Future work should investigate further destabilization from primer:target base mismatch through altered oligonucleotide chemistry or chemical additives.
Published: 2021

30. A human tau seeded neuronal cell model recapitulates molecular responses associated with Alzheimer's disease

Author: Elena Ficulle, Sarubini Kananathan, David Airey, Severine I. Gharbi, Neil Humphryes-Kirilov, James Scherschel, Charlotte Dunbar, Brian J. Eastwood, Emma Laing, David A. Collier, and Suchira Bose
Subjects: Neurons, Multidisciplinary, Gene Expression Regulation, Alzheimer Disease, Humans, tau Proteins, Transcriptome
Abstract: Cellular models recapitulating features of tauopathies are useful tools to investigate the causes and consequences of tau aggregation and the identification of novel treatments. We seeded rat primary cortical neurons with tau isolated from Alzheimer’s disease brains to induce a time-dependent increase in endogenous tau inclusions. Transcriptomics of seeded and control cells identified 1075 differentially expressed genes (including 26 altered at two time points). These were enriched for lipid/steroid metabolism and neuronal/glial cell development genes. 50 genes were correlated with tau inclusion formation at both transcriptomic and proteomic levels, including several microtubule and cytoskeleton-related proteins such as Tubb2a, Tubb4a, Nefl and Snca. Several genes (such as Fyn kinase and PTBP1, a tau exon 10 repressor) interact directly with or regulate tau. We conclude that this neuronal model may be a suitable platform for high-throughput screens for target or hit compound identification and validation.
Published: 2021

31. Overlap of expression and alignment of diurnal and circadian rhythmicity in the human blood transcriptome with organ and tissue specific rhythmicity in a non-human primate

Author: Derk-Jan Dijk, Carla S. Möller-Levet, Simon Archer, and Emma Laing
Subjects: Transcriptome, Rhythm, biology, Transcription (biology), Period (gene), biology.animal, Translation (biology), Circadian rhythm, Gene, Cell biology, Baboon
Abstract: BACKGROUNDTwenty-four-hour rhythmicity in transcriptomes of tissues and organs is driven by local circadian oscillators, systemic factors, the central circadian pacemaker, and light-dark cycles. This rhythmicity is to some extent organ- and tissue-specific such that the sets of rhythmic transcripts or their timing are different across tissues/organs. Monitoring rhythmicity of tissues and organs holds promise for circadian medicine, but in humans most tissues and organs are not easily accessible. To investigate the extent to which rhythmicity in the human blood transcriptome reflects rhythmicity in tissues and organs, we compared the overlap and timing of rhythmic transcripts in human blood and rhythmic transcripts in 64 tissues/organs of the baboon.METHODSRhythmicity in the transcriptomes of humans and baboons were compared using set logic, circular cross-correlation, circular clustering, functional enrichment analyses and partial least squares regression.RESULTSOf the 759 orthologous genes that were rhythmic in human blood, 652 (86%) were also rhythmic in at least one baboon tissue. Most of these genes were associated with basic processes such as transcription and protein homeostasis. 109 (17%) of the 652 overlapping rhythmic genes were reported as rhythmic in only one baboon tissue or organ and several of these genes have tissue/organ-specific functions. Analysis of the alignment between baboon and human transcriptomes showed that in these diurnal species, rhythmicity is aligned with the onset, rather than midpoint or end of light period. In both species, the timing of rhythmic transcripts displayed prominent ‘night’ and ‘day’ clusters, with genes in the dark cluster associated with translation. The timing of human and baboon transcriptomes was significantly correlated in 25 tissue/organs with an average earlier timing of 3.21 h (SD 2.47 h) in human blood.CONCLUSIONSThe human blood transcriptome contains sets of rhythmic genes that overlap with rhythmic genes of tissues/organs, some of which are tissue/organ-specific, in the baboon. The rhythmic sets vary across tissues/organs but the timing of most rhythmic genes is similar across human blood and baboon tissues/organs. These results have implications for our understanding of the regulation of rhythmicity across tissues/organs and species and development of blood transcriptome-based biomarkers for rhythmicity in tissues and organs.
Published: 2021

32. Tandem RNA isolation reveals functional rearrangement of RNA-binding proteins on CDKN1B/p27Kip1 3’UTRs in cisplatin treated cells

Author: Valentina Iadevaia, Alexander Kanitz, Maikel D. Wouters, André P. Gerber, Ana M. Matia-González, and Emma Laing
Subjects: RNA-binding protein, RNA Stability, drug response, Biology, Interactome, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Gene expression, Protein Interaction Mapping, Humans, mRNA stability, KHSRP, Protein Interaction Maps, RNA, Messenger, RNA Processing, Post-Transcriptional, Molecular Biology, 3' Untranslated Regions, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Messenger RNA, RNA, RNA-Binding Proteins, p27, Cell Biology, 3. Good health, Cell biology, HEK293 Cells, Gene Expression Regulation, Tandem Repeat Sequences, 030220 oncology & carcinogenesis, Gene Knockdown Techniques, RNA splicing, RNA extraction, Cisplatin, Post-transcriptional gene regulation, Cyclin-Dependent Kinase Inhibitor p27, Research Paper, Protein Binding
Abstract: Post-transcriptional control of gene expression is mediated via RNA-binding proteins (RBPs) that interact with mRNAs in a combinatorial fashion. While recent global RNA interactome capture experiments expanded the repertoire of cellular RBPs quiet dramatically, little is known about the assembly of RBPs on particular mRNAs; and how these associations change and control the fate of the mRNA in drug-treatment conditions. Here we introduce a novel biochemical approach, termed tobramycinbased tandem RNA isolation procedure (tobTRIP), to quantify proteins associated with the 3'UTRs of cyclin-dependent kinase inhibitor 1B (CDKN1B/p27Kip1) mRNAs in vivo. P27Kip1 plays an important role in mediating a cell's response to cisplatin (CP), a widely used chemotherapeutic cancer drug that induces DNA damage and cell cycle arrest. We found that p27Kip1 mRNA is stabilized upon CP treatment of HEK293 cells through elements in its 3'UTR. Applying tobTRIP, we further compared the associated proteins in CP and non-treated cells, and identified more than fifty interacting RBPs, many functionally related and evoking a coordinated response. Knock-downs of several of the identified RBPs in HEK293 cells confirmed their involvement in CP-induced p27 mRNA regulation; while knock-down of the KH-type splicing regulatory protein (KHSRP) further enhanced the sensitivity of MCF7 adenocarcinoma cancer cells to CP treatment. Our results highlight the benefit of specific in vivo mRNA-protein interactome capture to reveal post-transcriptional regulatory networks implicated in cellular drug response and adaptation.
Published: 2019

33. An inter-laboratory study to investigate the impact of the bioinformatics component on microbiome analysis using mock communities

Author: Grace Logan, Kathryn A. Harris, Josef Wagner, Jiabin Huang, Justin O'Grady, Julian R. Marchesi, Robert D. Finn, Sasithon Temisak, Huihai Wu, Nicole Fischer, Julian Parkhill, Ronan Doyle, Gregory C. A. Amos, Mark D. Preston, Denise M. O'Sullivan, Jacob Moran-Gilad, Nicholas Redshaw, Hubert Denise, Jim F. Huggett, Yair Motro, Jody Phelan, Alexandra S. Whale, Taane G. Clark, Emma Ransom-Jones, Ernest Diez Benavente, David J. Studholme, Emma Laing, Gemma L. Kay, Apollo - University of Cambridge Repository, and Parkhill, Julian [0000-0002-7069-5958]
Subjects: 0301 basic medicine, FASTQ format, Operational taxonomic unit, Science, 030106 microbiology, Computational biology, Biology, Genome, 03 medical and health sciences, RNA, Ribosomal, 16S, Sequencing, Digital polymerase chain reaction, Microbiome, 631/326/2565/2142, Multidisciplinary, Microbiota, 631/1647/514, article, Computational Biology, Sequence Analysis, DNA, Amplicon, 16S ribosomal RNA, 030104 developmental biology, Metagenomics, Medicine
Abstract: Funder: UK National Measurement System, Funder: NIHR BRC and NIHR Policy Research Programme (NIBSC Regulatory Science Research Unit), Funder: National Institute of Health Research (NIHR) Imperial Biomedical Research Centre (BRC), Funder: EMBL core funds, Funder: Quadram Institute Bioscience BBSRC Strategic Programme: Microbes in the Food Chain; Grant(s): BB/R012504/1) and its constituent projects BBS/E/F/000PR10348 and BBS/E/F/000PR10349, Despite the advent of whole genome metagenomics, targeted approaches (such as 16S rRNA gene amplicon sequencing) continue to be valuable for determining the microbial composition of samples. Amplicon microbiome sequencing can be performed on clinical samples from a normally sterile site to determine the aetiology of an infection (usually single pathogen identification) or samples from more complex niches such as human mucosa or environmental samples where multiple microorganisms need to be identified. The methodologies are frequently applied to determine both presence of micro-organisms and their quantity or relative abundance. There are a number of technical steps required to perform microbial community profiling, many of which may have appreciable precision and bias that impacts final results. In order for these methods to be applied with the greatest accuracy, comparative studies across different laboratories are warranted. In this study we explored the impact of the bioinformatic approaches taken in different laboratories on microbiome assessment using 16S rRNA gene amplicon sequencing results. Data were generated from two mock microbial community samples which were amplified using primer sets spanning five different variable regions of 16S rRNA genes. The PCR-sequencing analysis included three technical repeats of the process to determine the repeatability of their methods. Thirteen laboratories participated in the study, and each analysed the same FASTQ files using their choice of pipeline. This study captured the methods used and the resulting sequence annotation and relative abundance output from bioinformatic analyses. Results were compared to digital PCR assessment of the absolute abundance of each target representing each organism in the mock microbial community samples and also to analyses of shotgun metagenome sequence data. This ring trial demonstrates that the choice of bioinformatic analysis pipeline alone can result in different estimations of the composition of the microbiome when using 16S rRNA gene amplicon sequencing data. The study observed differences in terms of both presence and abundance of organisms and provides a resource for ensuring reproducible pipeline development and application. The observed differences were especially prevalent when using custom databases and applying high stringency operational taxonomic unit (OTU) cut-off limits. In order to apply sequencing approaches with greater accuracy, the impact of different analytical steps needs to be clearly delineated and solutions devised to harmonise microbiome analysis results.
Published: 2021

34. Oxidative stress induces coordinated remodeling of RNA-enzyme interactions

Author: André P. Gerber, Ibtissam Jabre, Ana M. Matia-González, and Emma Laing
Subjects: 0301 basic medicine, Science, Saccharomyces cerevisiae, 02 engineering and technology, medicine.disease_cause, Proteomics, Article, 03 medical and health sciences, proteomics, medicine, chemistry.chemical_classification, Multidisciplinary, biology, RNA, Enzyme Interaction, molecular network, 021001 nanoscience & nanotechnology, biology.organism_classification, Yeast, Cell biology, microbial metabolism, 030104 developmental biology, Enzyme, chemistry, Proteome, 0210 nano-technology, Oxidative stress
Abstract: Summary RNA-binding proteins (RBPs) are key post-transcriptional regulators that play a substantial role during stress adaptation. Recent proteome-wide surveys have uncovered a large number of new and “unconventional” RBPs such as metabolic enzymes, yet little is known about the reconfiguration of the RNA-binding proteome (RBPome) and RNA-enzyme interactions in response to cellular stress. Here, we applied RNA-interactome capture to monitor the dynamics of the mRBPome upon mild oxidative stress in the yeast Saccharomyces cerevisiae. Among the 257 proteins that significantly changed RNA associations, we observed the coordinated remodeling of RNA-binding enzymes — particularly of the central carbon metabolism — that complemented known metabolic responses. Furthermore, we recognized the propensity for paralogous specific alterations of enzyme-RNA interactions. Our results suggest coordinated cross talk between RNA-enzyme interactions and intermediary metabolism to maintain the physiological and molecular balance upon oxidative stress, perhaps through specialization of paralogous during evolution., Graphical abstract, Highlights • Oxidative stress induces the rearrangement of 257 proteins on polyadenylated RNAs • Coordinated response of RNA-enzyme interactions and metabolism • Yeast RNA-binding enzymes are paralog specific • Integration of three different mass spectrometry analysis tools, Molecular network; Microbial metabolism; Proteomics
Published: 2021

35. Virological and serological characterization of critically ill patients with COVID-19 in the UK: a special focus on variant detection

Author: D Nguyen, Emma Laing, Tanya Golubchik, W Slack, Lise J Estcourt, David Bonsall, Pat Tsang, J Rhynne, Paul R Mouncey, Rutger J. Ploeg, Heli Harvala, N Ciccone, U Leuscher, Manu Shankar-Hari, Aislinn Jennings, Sarah Williams, Matthew Fish, David K. Menon, Peter Simmonds, Kathy Rowan, Abigail Lamikanra, Farah Al-Beidh, Amy Evans, Sheba Ziyenge, David J. Roberts, Anthony C. Gordon, M Olivera, and Jeremy Ratcliff
Subjects: Coronavirus disease 2019 (COVID-19), biology, business.industry, Disease, Acquired immune system, Intensive care unit, law.invention, Serology, Randomized controlled trial, law, Immunology, biology.protein, Medicine, Antibody, business, Viral load
Abstract: BackgroundTreatment of COVID-19 patients with convalescent plasma containing neutralising antibody to SARS-CoV-2 is under investigation as a means of reducing viral loads, ameliorating disease outcomes, and reducing mortality. However, its efficacy might be reduced in those infected with the emerging B.1.1.7 SARS-CoV-2 variant. Here, we report the diverse virological characteristics of UK patients enrolled in the Immunoglobulin Domain of the REMAP-CAP randomised controlled trial.MethodsSARS-CoV-2 viral RNA was detected and quantified by real-time PCR in nasopharyngeal swabs obtained from study subjects within 48 hours of admission to intensive care unit. Antibody status was determined by spike-protein ELISA. B.1.1.7 strain was differentiated from other SARS-CoV-2 strains by two novel typing methods detecting the B.1.1.7-associated D1118H mutation with allele-specific probes and by restriction site polymorphism (SfcI).FindingsOf 1260 subjects, 90% were PCR-positive with viral loads in nasopharyngeal swabs ranging from 72 international units [IUs]/ml to 1.7×1011IU/ml. Median viral loads were 45-fold higher in those who were seronegative for IgG antibodies (n=314; 28%) compared to seropositives (n=804; 72%), reflecting in part the latter group’s possible later disease stage on enrolment. Frequencies of B.1.1.7 infection increased from early November (60%). Anti-SARS-CoV-2 seronegative individuals infected with wild-type SARS-CoV-2 had significantly higher viral loads than seropositives (medians of 1.2×106and 3.4 ×104IU/ml respectively; p=2×10−9). However, viral load distributions were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (13.4×106and 7.6×106IU/ml; p=0.18).InterpretationHigh viral loads in seropositive B.1.1.7-infected subjects are consistent with increased replication capacity and/or less effective clearance by innate or adaptive immune response of B.1.1.7 strain than wild-type. As viral genotype was associated with diverse virological and immunological phenotypes, metrics of viral load, antibody status and infecting strain should be used to define subgroups for analysis of treatment efficacy.
Published: 2021

36. Oxidative Stress Induces Remodelling of RNA-Enzyme Interactions within Carbon Metabolism

Author: André P. Gerber, Ana M. Matia-González, Emma Laing, and Ibtissam Jabre
Subjects: chemistry.chemical_classification, biology, Saccharomyces cerevisiae, RNA, RNA-binding protein, Enzyme Interaction, medicine.disease_cause, biology.organism_classification, Cell biology, Crosstalk (biology), Enzyme, chemistry, Proteome, medicine, Oxidative stress
Abstract: RNA-binding proteins (RBPs) are key post-transcriptional regulators that play a substantial role during stress adaptation. Recent proteome-wide surveys have uncovered a large number of new and ‘unconventional’ RBPs such as metabolic enzymes, yet little is known about the reconfiguration of the RNA-binding proteome (RBPome) and RNA-enzyme interactions in response to cellular stress. Here we applied RNA-interactome capture to monitor the dynamics of the RBPome upon mild oxidative stress in the yeast Saccharomyces cerevisiae. Among the 257 proteins that significantly changed RNA associations, we observed the coordinated remodeling of RNA-binding enzymes - particularly of the central carbon metabolism - that complemented known metabolic responses. Furthermore, we recognized the propensity for paralogous specific alterations of enzyme-RNA interactions. Our results suggest coordinated crosstalk between RNA-enzyme interactions and intermediary metabolism to maintain the physiological and molecular balance upon oxidative stress, perhaps through specialization of paralogous during evolution.
Published: 2021

37. Genetic underpinnings of sociability in the general population

Author: S.E.E.C. Bauduin, Alessandro Serretti, Geert Poelmans, Brenda W.J.H. Penninx, David A. Collier, Nina Roth Mota, Hilde de Kluiver, Celso Arango, Nic J.A. van der Wee, Barbara Franke, José Luis Ayuso-Mateos, Cornelius J. H. M. Klemann, Emma Laing, Ward De Witte, Janita Bralten, Chiara Fabbri, Martien J H Kas, Bralten J., Mota N.R., Klemann C.J.H.M., De Witte W., Laing E., Collier D.A., de Kluiver H., Bauduin S.E.E.C., Arango C., Ayuso-Mateos J.L., Fabbri C., Kas M.J., van der Wee N., Penninx B.W.J.H., Serretti A., Franke B., Poelmans G., Kas lab, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, and APH - Digital Health
Subjects: Adult, Bipolar Disorder, Population, Genome-wide association study, Disease, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, SNP, Genetic Predisposition to Disease, Bipolar disorder, education, 030304 developmental biology, Pharmacology, 0303 health sciences, education.field_of_study, Depressive Disorder, Major, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Depression, Autism spectrum disorders, medicine.disease, Psychiatry and Mental health, Schizophrenia, Behavioural genetics, Major depressive disorder, Autism, Psychology, 030217 neurology & neurosurgery, Clinical psychology, Genome-Wide Association Study, Human
Abstract: Contains fulltext : 237832.pdf (Publisher’s version ) (Open Access) Levels of sociability are continuously distributed in the general population, and decreased sociability represents an early manifestation of several brain disorders. Here, we investigated the genetic underpinnings of sociability in the population. We performed a genome-wide association study (GWAS) of a sociability score based on four social functioning-related self-report questions from 342,461 adults in the UK Biobank. Subsequently we performed gene-wide and functional follow-up analyses. Robustness analyses were performed in the form of GWAS split-half validation analyses, as well as analyses excluding neuropsychiatric cases. Using genetic correlation analyses as well as polygenic risk score analyses we investigated genetic links of our sociability score to brain disorders and social behavior outcomes. Individuals with autism spectrum disorders, bipolar disorder, depression, and schizophrenia had a lower sociability score. The score was significantly heritable (SNP h(2) of 6%). We identified 18 independent loci and 56 gene-wide significant genes, including genes like ARNTL, DRD2, and ELAVL2. Many associated variants are thought to have deleterious effects on gene products and our results were robust. The sociability score showed negative genetic correlations with autism spectrum, disorders, depression, schizophrenia, and two sociability-related traits-loneliness and social anxiety-but not with bipolar disorder or Alzheimer's disease. Polygenic risk scores of our sociability GWAS were associated with social behavior outcomes within individuals with bipolar disorder and with major depressive disorder. Variation in population sociability scores has a genetic component, which is relevant to several psychiatric disorders. Our findings provide clues towards biological pathways underlying sociability.
Published: 2021

38. Multicentre randomised controlled trial: protocol for Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO)

Author: Wesley Hayes, Emma Laing, Claire Foley, Laura Pankhurst, Helen Thomas, Helen Hume-Smith, Stephen Marks, Nicos Kessaris, William A Bryant, Anastassia Spiridou, Jo Wray, and Mark J Peters
Subjects: Sodium Acetate, Sodium, Magnesium Chloride, General Medicine, Sodium Chloride, Gluconates, Kidney Transplantation, Potassium Chloride, Electrolytes, Humans, Multicenter Studies as Topic, Child, Hyponatremia, Randomized Controlled Trials as Topic
Abstract: IntroductionAcute electrolyte and acid–base imbalance is experienced by many children following kidney transplantation. When severe, this can lead to complications including seizures, cerebral oedema and death. Relatively large volumes of intravenous fluid are administered to children perioperatively in order to establish perfusion to the donor kidney, the majority of which are from living and deceased adult donors. Hypotonic intravenous fluid is commonly used in the post-transplant period due to clinicians’ concerns about the sodium, chloride and potassium content of isotonic alternatives when administered in large volumes.Plasma-Lyte 148 is an isotonic, balanced intravenous fluid that contains sodium, chloride, potassium and magnesium with concentrations equivalent to those of plasma. There is a physiological basis to expect that Plasma-Lyte 148 will reduce the incidence of clinically significant electrolyte and acid–base abnormalities in children following kidney transplantation compared with current practice.The aim of the PLUTO trial is to determine whether the incidence of clinically significantly abnormal plasma electrolyte levels in paediatric kidney transplant recipients will be different with the use of Plasma-Lyte-148 compared to intravenous fluid currently administered.Methods and analysisPLUTO is a pragmatic, open-label, randomised controlled trial comparing Plasma-Lyte 148 to current care in paediatric kidney transplant recipients, conducted in nine UK paediatric kidney transplant centres.A total of 144 children receiving kidney transplants will be randomised to receive either Plasma-Lyte 148 (the intervention) intraoperatively and postoperatively, or current fluid. Apart from intravenous fluid composition, all participants will receive standard clinical transplant care.The primary outcome measure is acute hyponatraemia in the first 72 hours post-transplant, defined as laboratory plasma sodium concentration of The primary outcome will be analysed using a logistic regression model adjusting for donor type (living vs deceased donor), patient weight (Ethics and disseminationThe trial received Health Research Authority approval on 20 January 2020. Findings will be presented to academic groups via national and international conferences and peer-reviewed journals. The patient and public involvement group will play an important part in disseminating the study findings to the public domain.Trial registration numbers2019-003025-22 and 16586164.
Published: 2022

39. Use of Granulocyte Transfusions in Two National Cohorts and Association between Transfusion Dose and Patient Outcomes: The Best Collaborative Study

Author: Joseph Parsons, Claire Boulat, Jeffrey McCullough, Ruth H. Keogh, Lorna Cain, Elisa Allen, Simon J. Stanworth, Emma Laing, Monica B. Pagano, Domenico Francis-Radice, Suzy Morton, Jennifer Thompson, and Pierre Tiberghien
Subjects: medicine.medical_specialty, medicine.anatomical_structure, business.industry, Internal medicine, Immunology, Medicine, Cell Biology, Hematology, Granulocyte, business, Association (psychology), Biochemistry
Abstract: Granulocytes for transfusion (GTX) continue to be administered, mostly to treat refractory infection 1. Single center series continue to be reported, but evidence of GTX effectiveness remains uncertain. Recent attempts at randomized trials of GTX have not been completed to target although the largest trial, RING 2, identified potentially promising results in a sub-group analysis by dose. GTX can be produced by apheresis (from 'stimulated' donors), aGTX, or as a component pooled from whole blood (WB) donations. Logistic difficulties arise with aGTX, including recruitment of suitable donors willing to undergo cell mobilization and collection. In England GTX are now only supplied as pooled (10 WB donations/pool, mean volume single pooled unit 207 ml, mean granulocyte yield/unit 0.9 x10 10, typical adult dose 2 pools, available 6 days per week). In France, production moved from aGTX to pooled in 2020 (20 WB donations/pool, mean volume single pooled component 428 ml, mean granulocyte yield/unit 1.8 x10 10, typical adult dose 1 pool, available 6 days per week). There have been no recent published national data on the clinical use of pooled granulocytes, or comparisons between large datasets. The aim of this study was to 1) describe the use of GTX, including pooled granulocytes, in two national cohorts of recipients; 2) estimate the effect of dose on patient mortality using statistical methods which could be applied to a larger dataset in the future. A pre-piloted data collection form (DCF) was used to collect prospective audit data on all GTX given to patients in participating hospitals in England from March 2017 -Sept 2020 in England. The PROspective Granulocyte usage and outcomEs Survey (ProGrES) was deemed a national registry/audit with no individual patient consent required for anonymized data. Information on patient characteristics and outcomes was collected at the time of the request for GTX, following completion of GTX and at 28 days and 6 months follow up. DCFs were adapted for international use, and French data were collected from Jan 2018 to Dec 2020. Descriptive analyses were performed to summarize GTX dose, patient characteristics, and outcomes. Using the English data, we investigated the association between GTX dose and mortality within 28 days of final GTX using logistic regression models with and without adjustment for possible confounders (age, infection source, use of renal therapy) and using the target trial framework. Ethical approval was obtained from London School of Hygiene and Tropical Medicine for analysis of English data. Results are presented on 224 (England, pooled) and 139 (France) patients who received GTX. In France, 95 and 44 patients received aGTX and pooled GTX, respectively. Table 1 shows patient features and outcomes. The most frequent underlying diagnosis was acute myeloid leukemia in all groups, and the most common indication was treatment of refractory infection. Median number of transfusions was similar in all groups (5.0, 5.3, 6.0). The mean dose/kg/transfusion was highest in the aGTX group (0.55 x10 9/kg), followed by French pooled (0.40) and English pooled (0.2). Death within 28 days of last GTX varied from 20.2% (French apheresis) to 32.5% (French pooled). Additional analyses were performed on the English data; for death within 28 days, a 0.1 x10 9 increase in GTX dose was associated with a 22% reduction (95% CI -45% to +0%) in odds of death within 28 days of referral; odds ratio 0.78 (95% CI 0.57 to 1.00). After adjustment for potential confounders, the odds ratio was attenuated to 0.92 (95% CI 0.67, 1.23). In summary, GTX continue to be requested by clinicians in patients with poor outcomes, despite an uncertain evidence-base. Regression analysis found dose was associated with lower odds of 28-day mortality. This was not significant after confounder adjustment, but this proof-of-principle analysis was limited by the sample size. A potential dose effect was also seen in the RING study. Our analysis using a target trial approach provides an approach for estimating GTX effectiveness in a larger cohort, which is required given the well-recognized challenges of undertaking randomized trials. The analysis provides a range of sample size calculations for testing an association between dose and outcomes for a defined effect size in a larger international cohort, supported by the BEST Collaborative 3. References: 1. Transfusion 2019;59(1)160 2. Blood 2015;126(18)2153 3. Transfus Med Hemother 2018(45)318 Figure 1 Figure 1. Disclosures Francis-Radice: GSK: Current equity holder in publicly-traded company; Smith & Nephew: Current equity holder in publicly-traded company; Bunzl: Current equity holder in publicly-traded company; Relx: Current equity holder in publicly-traded company; Cancer Research UK: Research Funding. McCullough: Fresenius Kabi: Honoraria; Terumo BCT: Honoraria.
Published: 2021

40. A systematic evaluation of Mycobacterium tuberculosis Genome-Scale Metabolic Networks

Author: Luis F. Barrera, Dany J. V. Beste, Tom A. Mendum, Víctor A. López-Agudelo, Emma Laing, Rigoberto Ríos-Estepa, and Andres Baena
Subjects: Mycobacterium tuberculosis, Future studies, biology, Multiple Models, Systems biology, Research community, Genome scale, Metabolic network, Computational biology, Model choice, respiratory system, bacterial infections and mycoses, biology.organism_classification
Abstract: The metabolism of the causative agent of TB, Mycobacterium tuberculosis (Mtb) has recently re-emerged as an attractive drug target. A powerful approach to study Mtb metabolism is to use a systems biology framework, such as a Genome-Scale Metabolic Network (GSMN) that allows the dynamic interactions of the many individual components of metabolism to be interrogated together. Several GSMNs networks have been constructed for Mtb and used to study the complex relationship between Mtb genotype and phenotype. However, their utility is hampered by the existence of multiple models of varying properties and performances. Here we systematically evaluate eight recently published metabolic models of Mtb-H37Rv to facilitate model choice. The best performing models, sMtb2018 and iEK1011, were refined and improved for use in future studies by the TB research community.
Published: 2019

41. Surveillance arterioveNous fistulAs using ultRasound (SONAR) trial in haemodialysis patients: a study protocol for a multicentre observational study

Author: Paul J. Gibbs, Vasilis Kosmoliaptsis, Sarah Lawman, Claire Foley, Andrew L. Tambyraja, Valerie Hopkins, Sam Dutta, H.L. Thomas, Tracey Salter, Anna Sidders, Simon R. Knight, Gavin J. Pettigrew, Matthew Bartlett, Reza Motallebzadeh, Zia Moinuddin, Sam Turner, Mohammed Hossain, Dominic M. Summers, Edward C. F. Wilson, Mohammed Aslam, George Smith, James P. Hunter, Subash Somalanka, Rajesh Sivaprakasam, Regin Lagaac, Matthew Slater, Emma Laing, Chloe Fitzpatrick-Creamer, Cara Hudson, James A Richards, Atul Bagul, Nicholas Barnett, Richards, James [0000-0001-9049-5745], Kosmoliaptsis, Vasilis [0000-0001-7298-1387], Wilson, Edward Cf [0000-0002-8369-1577], Laing, Emma [0000-0002-8309-0990], Salter, Tracey [0000-0002-4857-0358], and Apollo - University of Cambridge Repository
Subjects: medicine.medical_specialty, medicine.medical_treatment, Fistula, Population, 030232 urology & nephrology, Arteriovenous fistula, 030204 cardiovascular system & hematology, end stage renal failure, surgery, 03 medical and health sciences, 0302 clinical medicine, Arteriovenous Shunt, Surgical, Renal Dialysis, Protocol, medicine, Vascular Patency, Humans, Multicenter Studies as Topic, education, Dialysis, education.field_of_study, business.industry, ultrasound, General surgery, Ultrasonography, Doppler, General Medicine, medicine.disease, Observational Studies as Topic, Arteriovenous Fistula, dialysis, Observational study, business, Central venous catheter
Abstract: IntroductionArteriovenous fistulas (AVFs) are considered the best and safest modality for providing haemodialysis in patients with end-stage renal disease. Only 20% of UK centres achieve the recommended 80% target for achieving dialysis of the prevalent dialysis population via permanent access (as opposed to a central venous catheter). This is partly due to the relatively poor maturation rate of newly created fistulas, with as many as 50% of fistulas failing to mature.The Surveillance Of arterioveNous fistulAe using ultRasound study will examine whether a protocolised programme of Doppler ultrasound (US) surveillance can identify, early after creation, potentially correctable problems in those AVFs that subsequently fail to mature.Methods and analysisThis is a multicentre observational study that will assess newly created AVFs by Doppler US performed at 2, 4, 6 and 10 weeks after creation. The primary outcome measure will be primary fistula patency at week 10. Secondary outcome measures include: successful use of the fistula; clinical suitability for dialysis; creation of new fistula or radiological salvage; fistula thrombosis; secondary fistula patency rate and patient acceptability.Ethics and disseminationThe study has been approved by the Cambridgeshire and Hertfordshire Research Ethics Committee and by the Health Research Authority (REC 18/EE/0234). The results generated from this work will be published as open access, within 3 years of trial commencement. We will also present our findings at key national/international renal meetings, as well as support volunteers at renal patient groups to disseminate the trial outcome.Trial registration numberISRCTN36033877
Published: 2019

42. Circadian regulation in human white adipose tissue revealed by transcriptome and metabolic network analysis

Author: Jonathan D. Johnston, Victoria L. Revell, Cheryl Isherwood, Huihai Wu, Skevoulla Christou, Carla S. Möller-Levet, Debra J. Skene, Emma Laing, Sophie M T Wehrens, Giselda Bucca, and Simon Archer
Subjects: 0301 basic medicine, Adipose Tissue, White, lcsh:Medicine, Adipose tissue, White adipose tissue, Biology, Article, Nucleic acid metabolism, Transcriptome, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Circadian Clocks, Animals, Humans, Circadian rhythm, lcsh:Science, Regulation of gene expression, Multidisciplinary, Gene Expression Profiling, lcsh:R, Computational Biology, Lipid metabolism, Circadian Rhythm, Cell biology, Metabolic pathway, 030104 developmental biology, Gene Expression Regulation, chemistry, lcsh:Q, Energy Metabolism, Metabolic Networks and Pathways, 030217 neurology & neurosurgery
Abstract: Studying circadian rhythms in most human tissues is hampered by difficulty in collecting serial samples. Here we reveal circadian rhythms in the transcriptome and metabolic pathways of human white adipose tissue. Subcutaneous adipose tissue was taken from seven healthy males under highly controlled ‘constant routine’ conditions. Five biopsies per participant were taken at six-hourly intervals for microarray analysis and in silico integrative metabolic modelling. We identified 837 transcripts exhibiting circadian expression profiles (2% of 41619 transcript targeting probes on the array), with clear separation of transcripts peaking in the morning (258 probes) and evening (579 probes). There was only partial overlap of our rhythmic transcripts with published animal adipose and human blood transcriptome data. Morning-peaking transcripts associated with regulation of gene expression, nitrogen compound metabolism, and nucleic acid biology; evening-peaking transcripts associated with organic acid metabolism, cofactor metabolism and redox activity. In silico pathway analysis further indicated circadian regulation of lipid and nucleic acid metabolism; it also predicted circadian variation in key metabolic pathways such as the citric acid cycle and branched chain amino acid degradation. In summary, in vivo circadian rhythms exist in multiple adipose metabolic pathways, including those involved in lipid metabolism, and core aspects of cellular biochemistry.
Published: 2019

43. Transcriptional signatures of progressive neuropathology in transgenic tau and amyloid mouse models

Author: Paul O'Neill, Tracey K. Murray, O’Neil Mj, Andrew D. Randall, Aaron R. Jeffries, David A. Collier, Hedley Baulf, Karen M Moore, J. Mill, Emma Walker, Eilis Hannon, Isabel Castanho, Joshua Harvey, Katie Lunnon, Zeshan Ahmed, and Emma Laing
Subjects: 0303 health sciences, Neocortex, biology, Amyloid, Transgene, Tau protein, Genome-wide association study, Neuropathology, Entorhinal cortex, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, biology.protein, Amyloid precursor protein, medicine, Neuroscience, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: The onset and progression of Alzheimer’s disease (AD) is characterized by increasing intracellular aggregation of hyperphosphorylated tau protein and accumulation of β-amyloid (Aβ) in the neocortex. Despite recent success in identifying genetic risk factors for AD the transcriptional mechanisms involved in disease progression are not fully understood. We used transgenic mice harbouring human tau (rTg4510) and amyloid precursor protein (J20) mutations to investigate transcriptional changes associated with the development of both tau and amyloid pathology. Using highly-parallel RNA sequencing we profiled transcriptional variation in the entorhinal cortex at four time points identifying robust genotype-associated differences in entorhinal cortex gene expression in both models. We quantified neuropathological burden across multiple brain regions in the same individual mice, identifying widespread changes in gene expression paralleling the development of tau pathology in rTg4510 mice. Differentially expressed transcripts included genes associated with familial AD from genetic studies of human patients, and genes annotated to both common and rare variants identified in GWAS and exome-sequencing studies of late-onset sporadic AD. Systems-level analyses identified discrete co-expression networks associated with the progressive accumulation of tau, with these enriched for genes and pathways previously implicated in the neuro-immunological and neurodegenerative processes driving AD pathology. Finally, we report considerable overlap between tau-associated networks and AD-associated co-expression modules identified in the human cortex. Our data provide further support for an immune-response component in the accumulation of tau, and reveal novel molecular pathways associated with the progression of AD neuropathology.
Published: 2019

44. REM sleep's unique associations with corticosterone regulation, apoptotic pathways, and behavior in chronic stress in mice

Author: Carla S. Möller-Levet, Harriet Hicks, Nathan Lawless, Andrew McCarthy, Derk-Jan Dijk, Keith A. Wafford, Raphaelle Winsky-Sommerer, Huihai Wu, Emma Laing, Karim Malki, and Mathieu Nollet
Subjects: Male, Hippocampus, Sleep, REM, Apoptosis, Biology, medicine.disease_cause, Transcriptome, chemistry.chemical_compound, Mice, Corticosterone, medicine, Animals, Chronic stress, Wakefulness, Prefrontal cortex, Mice, Inbred BALB C, Multidisciplinary, Behavior, Animal, Anhedonia, Electroencephalography, Biological Sciences, Sleep in non-human animals, anhedonia, Phenotype, machine learning, chemistry, PNAS Plus, Chronic Disease, depression, sense organs, EEG theta power, medicine.symptom, Neuroscience, Oxidative stress, psychological phenomena and processes, Stress, Psychological
Abstract: Significance Sleep disturbances are common in stress-related disorders but the nature of these sleep disturbances and how they relate to changes in the stress hormone corticosterone and changes in gene expression remained unknown. Here we demonstrate that in response to chronic mild stress, rapid–eye-movement sleep (REMS), a sleep state involved in emotion regulation and fear conditioning, changed first and more so than any other measured sleep characteristic. Transcriptomic profiles related to REMS continuity and theta oscillations overlapped with those for corticosterone, as well as with predictors for anhedonia, and were enriched for apoptotic pathways. These data highlight the central role of REMS in response to stress and warrant further investigation into REMS’s involvement in stress-related mental health disorders., One of sleep’s putative functions is mediation of adaptation to waking experiences. Chronic stress is a common waking experience; however, which specific aspect of sleep is most responsive, and how sleep changes relate to behavioral disturbances and molecular correlates remain unknown. We quantified sleep, physical, endocrine, and behavioral variables, as well as the brain and blood transcriptome in mice exposed to 9 weeks of unpredictable chronic mild stress (UCMS). Comparing 46 phenotypic variables revealed that rapid–eye-movement sleep (REMS), corticosterone regulation, and coat state were most responsive to UCMS. REMS theta oscillations were enhanced, whereas delta oscillations in non-REMS were unaffected. Transcripts affected by UCMS in the prefrontal cortex, hippocampus, hypothalamus, and blood were associated with inflammatory and immune responses. A machine-learning approach controlling for unspecific UCMS effects identified transcriptomic predictor sets for REMS parameters that were enriched in 193 pathways, including some involved in stem cells, immune response, and apoptosis and survival. Only three pathways were enriched in predictor sets for non-REMS. Transcriptomic predictor sets for variation in REMS continuity and theta activity shared many pathways with corticosterone regulation, in particular pathways implicated in apoptosis and survival, including mitochondrial apoptotic machinery. Predictor sets for REMS and anhedonia shared pathways involved in oxidative stress, cell proliferation, and apoptosis. These data identify REMS as a core and early element of the response to chronic stress, and identify apoptosis and survival pathways as a putative mechanism by which REMS may mediate the response to stressful waking experiences.
Published: 2019

45. Pre-Implantation trial of Histopathology In renal Allografts (PITHIA): A stepped-wedge cluster randomised controlled trial protocol

Author: Alison J Deary, Desley Neil, Dominic M. Summers, Laura Pankhurst, Emma Laing, Gavin J. Pettigrew, John O O Ayorinde, Karla Hemming, Victoria Bardsley, Edward C. F. Wilson, Ayorinde, John Oo [0000-0001-6603-0139], Laing, Emma [0000-0002-8309-0990], Wilson, Edward Cf [0000-0002-8369-1577], and Apollo - University of Cambridge Repository
Subjects: medicine.medical_specialty, Cost-Benefit Analysis, Renal function, 030230 surgery, Kidney, 03 medical and health sciences, 0302 clinical medicine, Biopsy, medicine, Pathology, Protocol, health economics, Humans, Multicenter Studies as Topic, biopsy, 030212 general & internal medicine, Cluster randomised controlled trial, Registries, Randomized Controlled Trials as Topic, Research ethics, Health economics, medicine.diagnostic_test, business.industry, Graft Survival, General Medicine, renal transplantation, Allografts, Kidney Transplantation, Transplant Recipients, United Kingdom, medicine.anatomical_structure, stepped-wedge, transplant surgery, Emergency medicine, Economic evaluation, histopathology, Histopathology, business
Abstract: IntroductionMost potential kidney transplant donors in the UK are aged over 60 years, yet increasing donor age is associated with poorer graft survival and function. Urgent preimplantation kidney biopsy can identify chronic injury, and may aid selection of better ‘quality’ kidneys from this group. However, the impact of biopsy on transplant numbers remains unproven. The PreImplantation Trial of Histopathology In renal Allografts (PITHIA) study will assess whether the introduction of a national, 24 hours, digital histopathology service increases the number, and improves outcomes, of kidneys transplanted in the UK from older deceased donors.Methods and analysisPITHIA is an open, multicentre, stepped-wedge cluster randomised study, involving all UK adult kidney transplant centres. At 4-monthly intervals, a group of 4–5 randomly selected clusters (transplant centres) will be given access to remote, urgent, digital histopathology (total intervention period, 24 months). The trial has two primary end points: it is powered for an 11% increase in the proportion of primary kidney offers from deceased donors aged over 60 years that are transplanted, and a 6 mL/min increase in the estimated glomerular filtration rate of recipients at 12 months post-transplant. This would equate to an additional 120 kidney transplants performed in the UK annually. Trial outcome data will be collected centrally via the UK Transplant Registry held by NHS Blood and Transplant (NHSBT) and will be analysed using mixed effects models allowing for clustering within centres and adjusting for secular trends. An accompanying economic evaluation will estimate the cost-effectiveness of the service to the National Health Service.Ethics and disseminationThe study has been given favourable ethical opinion by the Cambridge South Research Ethics Committee and is approved by the Health Research Authority. We will present our findings at key transplant meetings, publish results within 4 years of the trial commencing and support volunteers at renal patient groups to disseminate the trial outcome.Trial registrationnumberISRCTN11708741; Pre-results.
Published: 2019

46. Transcriptional Signatures of Progressive Neuropathology in Transgenic Models of Tau and Amyloid Pathology

Author: Andrew D. Randall, Jonathan Mill, Emma Laing, Tracey K. Murray, Karen Moore, Hedley Baulf, Michael J. O’Neil, Eilis Hannon, Aaron R. Jeffries, David A. Collier, Paul O'Neill, Joshua Harvey, Isabel Castanho, Emma Walker, and Zeshan Ahmed
Subjects: Neocortex, medicine.anatomical_structure, Amyloid, Transgene, Tau protein, Amyloid precursor protein, biology.protein, medicine, Neuropathology, Biology, Entorhinal cortex, Neuroscience, Transgenic Model
Abstract: The onset and progression of Alzheimer’s disease (AD) is characterized by increasing intracellular aggregation of hyperphosphorylated tau protein and the accumulation of β-amyloid (Aβ) in the neocortex. Despite recent success in identifying genetic risk factors for AD, the transcriptional mechanisms involved in disease progression are not fully understood. We used transgenic mice harbouring human tau (rTg4510) and amyloid precursor protein (J20) mutations to investigate transcriptional changes associated with the development of both tau and amyloid pathology. Using highly-parallel RNA sequencing we profiled transcriptional variation in the entorhinal cortex at four time points identifying robust genotype-associated differences in entorhinal cortex gene expression in both models. We quantified neuropathological burden across multiple brain regions in the same individual mice, identifying widespread changes in gene expression paralleling the development of tau pathology in rTg4510 mice. There was a striking overlap between differentially expressed transcripts and genes associated with familial AD from genetic studies of human patients, and genes annotated to both common and rare variants identified in genome-wide association and exome-sequencing studies of late-onset sporadic AD. Systems-level analyses identified discrete co-expression networks associated with the progressive accumulation of tau, with these enriched for genes and pathways previously implicated in the neuro-immunological and neurodegenerative processes driving AD pathology. Finally, we report a highly-significant overlap between tau-associated networks and AD-associated co-expression modules identified in analyses of post-mortem human cortex. This study represents the most systematic analysis of progressive changes in gene expression in mouse models of AD pathology and the first to focus specifically on the entorhinal cortex, a key region affected early in human Alzheimer’s disease (AD). Our data provide further strong for an immune-response component in the accumulation of tau, and reveal novel molecular pathways associated with the progression of AD neuropathology.
Published: 2019

47. Modeling dynamic gene expression in STREPTOMYCES COELICOLOR: Comparing single and multi‐objective setups

Author: Spencer A. Thomas, Colin P. Smith, Yaochu Jin, and Emma Laing
Subjects: Genetics, biology, education, Streptomyces coelicolor, Gene expression, Gene regulatory network, Evolutionary algorithm, ComputingMethodologies_GENERAL, Computational biology, biology.organism_classification, humanities, Evolutionary computation
Abstract: "This book is a step-by-step guideline for research in gene regulatory networks (GRN) using evolutionary computation (EC)"-- This book serves as a handbook for gene regulatory network research using evolutionary algorithms, with ...
Published: 2016

48. Transcriptional Signatures of Tau and Amyloid Neuropathology

Author: Hedley Baulf, Paul O'Neill, Andrew D. Randall, Jonathan Mill, Tracey K. Murray, David A. Collier, Karen Moore, Michael J. O'Neill, Zeshan Ahmed, Emma Walker, Lauren Bradshaw, Eilis Hannon, Emma Laing, Aaron R. Jeffries, Katie Lunnon, Joshua Harvey, and Isabel Castanho
Subjects: 0301 basic medicine, Genetically modified mouse, Amyloid, hippocampus, Hippocampus, Mice, Transgenic, tau Proteins, Neuropathology, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, mental disorders, medicine, Amyloid precursor protein, Animals, Humans, tau, lcsh:QH301-705.5, neuropathology, Amyloid beta-Peptides, Neocortex, entorhinal cortex, amyloid, Entorhinal cortex, 3. Good health, Cortex (botany), Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), transgenic model, gene expression, Disease Progression, biology.protein, RNA-seq, Alzheimer’s disease, Neuroscience, 030217 neurology & neurosurgery
Abstract: Summary Alzheimer’s disease (AD) is associated with the intracellular aggregation of hyperphosphorylated tau and the accumulation of β-amyloid in the neocortex. We use transgenic mice harboring human tau (rTg4510) and amyloid precursor protein (J20) mutations to investigate transcriptional changes associated with the progression of tau and amyloid pathology. rTg4510 mice are characterized by widespread transcriptional differences in the entorhinal cortex with changes paralleling neuropathological burden across multiple brain regions. Differentially expressed transcripts overlap with genes identified in genetic studies of familial and sporadic AD. Systems-level analyses identify discrete co-expression networks associated with the progressive accumulation of tau that are enriched for genes and pathways previously implicated in AD pathology and overlap with co-expression networks identified in human AD cortex. Our data provide further evidence for an immune-response component in the accumulation of tau and reveal molecular pathways associated with the progression of AD neuropathology., Graphical Abstract, Highlights • Mice with human tau and amyloid mutations develop progressive neuropathology • We identify transcriptional changes associated with tau and amyloid pathology • Discrete co-expression networks are associated with the progression of tau pathology • These are enriched for genes and pathways implicated in the onset of human AD, Castanho et al. use transgenic mice harboring human tau and amyloid precursor protein mutations to identify transcriptional changes associated with the progression of Alzheimer’s disease (AD) pathology. Their data support an immune-response component in the accumulation of tau and reveal molecular pathways associated with AD neuropathology.
Published: 2020

49. REM sleep: unique associations with behavior, corticosterone regulation and apoptotic pathways in chronic stress in mice

Author: Emma Laing, Nathan Lawless, Mathieu Nollet, Andrew McCarthy, Harriet Hicks, Karim Malki, Raphaelle Winsky-Sommerer, Huihai Wu, Carla S. Möller-Levet, Keith A. Wafford, and Derk-Jan Dijk
Subjects: Mechanism (biology), Hippocampus, Anhedonia, Biology, Sleep in non-human animals, chemistry.chemical_compound, chemistry, Corticosterone, medicine, Chronic stress, Wakefulness, medicine.symptom, Prefrontal cortex, Neuroscience, psychological phenomena and processes
Abstract: One of sleep’s putative functions is mediation of adaptation to waking experiences. Chronic stress is a common waking experience, however, which specific aspect of sleep is most responsive, and how sleep changes relate to behavioral disturbances and molecular correlates remain unknown. We quantified sleep, physical, endocrine and behavioral variables and the brain and blood transcriptome in mice exposed to nine weeks of unpredictable chronic mild stress (UCMS). Comparing 46 phenotypical variables revealed that rapid-eye-movement sleep (REMS), corticosterone regulation and coat state were most responsive to UCMS. REMS theta oscillations were enhanced whereas delta oscillations in non-REMS were unaffected. Transcripts affected by UCMS in the prefrontal cortex, hippocampus, hypothalamus and blood were associated with inflammatory and immune responses. A machine learning approach controlling for unspecific UCMS effects identified transcriptomic predictors for specific phenotypes and their overlap. Transcriptomic predictor sets for the inter-individual variation in REMS continuity and theta activity shared many pathways with corticosterone regulation and in particular pathways implicated in apoptosis, including mitochondrial pathways. Predictor sets for REMS and anhedonia, one of the behavioral changes following UCMS, shared pathways involved in oxidative stress, cell proliferation and apoptosis. RNA predictor sets for non-NREMS parameters showed no overlap with other phenotypes. These novel data identify REMS as a core and early element of the response to chronic stress, and identify apoptotic pathways as a putative mechanism by which REMS mediates adaptation to stressful waking experiences.Significance StatementSleep is responsive to experiences during wakefulness and is altered in stress-related disorders. Whether sleep changes primarily concern rapid-eye-movement sleep (REMS) or non-REM sleep, and how they correlate with stress hormones, behavioral and transcriptomic responses remained unknown. We demonstrate using unpredictable chronic (9-weeks) mild stress that REMS is the most responsive of all the measured sleep characteristics, and correlates with deficiency in corticosterone regulation. An unbiased machine learning, controlling for unspecific effects of stress, revealed that REMS correlated with RNA predictor sets enriched in apoptosis including mitochondrial pathways. Several pathways were shared with predictors of corticosterone and behavioral responses. This unbiased approach point to apoptosis as a molecular mechanism by which REMS mediates adaptation to an ecologically relevant waking experience.
Published: 2018
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50. PREMONition: An algorithm for predicting the circadian clock-regulated molecular network

Author: Zheng Eelderink-Chen, Martha Merrow, Emma Laing, and Bosman J
Subjects: 0303 health sciences, biology, Circadian clock, Saccharomyces cerevisiae, Computational biology, biology.organism_classification, Homology (biology), CLOCK, 03 medical and health sciences, 0302 clinical medicine, Gene expression, Zeitgeber, Molecular clock, Gene, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: A transcriptional feedback loop is central to clock function in animals, plants and fungi. The clock genes involved in its regulation are specific to - and highly conserved within - the kingdoms of life. However, other shared clock mechanisms, such as phosphorylation, are mediated by proteins found broadly among living organisms, performing functions in many cellular sub-systems. Use of homology to directly infer involvement/association with the clock mechanism in new, developing model systems, is therefore of limited use. Here we describe the approach PREMONition,PREdictingMolecularNetworks, that uses functional relationships to predict molecular circadian clock associations. PREMONition is based on the incorporation of proteins encoded by known clock genes (when available), rhythmically expressed clock-controlled genes and non-rhythmically expressed but interacting genes into a cohesive network. After tuning PREMONition on the networks derived for human, fly and fungal circadian clocks, we deployed the approach to predict a molecular clock network forSaccharomyces cerevisiae, for which there are no readily-identifiable clock gene homologs. The predicted network was validated using gene expression data and a growth assay for sensitivity to light, a zeitgeber of circadian clocks of most organisms. PREMONition may be used to identify candidate clock-regulated processes and thus candidate clock genes in other organisms.
Published: 2018

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