Publications
1331 results found
Al Saikhan L, Park C, Tillin T, et al., 2022, Relationship Between Image Quality and Bias in 3D Echocardiographic Measures: Data From the SABRE (Southall and Brent Revisited) Study, JOURNAL OF THE AMERICAN HEART ASSOCIATION, Vol: 11
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- Citations: 3
Howe LJ, Nivard MG, Morris TT, et al., 2022, Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects, NATURE GENETICS, Vol: 54, Pages: 581-+, ISSN: 1061-4036
Charalambous C, Moon JC, Holly JMP, et al., 2022, Declining Levels and Bioavailability of IGF-I in Cardiovascular Aging Associate With QT Prolongation-Results From the 1946 British Birth Cohort, FRONTIERS IN CARDIOVASCULAR MEDICINE, Vol: 9, ISSN: 2297-055X
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- Citations: 1
Elliott HR, Burrows K, Min JL, et al., 2022, Characterisation of ethnic differences in DNA methylation between UK resident South Asians and Europeans
<jats:title>Abstract</jats:title><jats:p>Ethnic differences in non-communicable disease risk have been described between individuals of South Asian and European ethnicity that are only partially explained by genetics and other known risk factors. DNA methylation is one underexplored mechanism that may explain differences in disease risk. Currently there is little knowledge of how DNA methylation varies between South Asian and European ethnicities.</jats:p><jats:p>This study characterised differences in blood DNA methylation between individuals of self-reported European and South Asian ethnicity from two UK-based cohorts; Southall and Brent Revisited (SABRE) and Born in Bradford (BiB). DNA methylation differences between ethnicities were widespread throughout the genome (n=16,433 CpG sites, 3.4% sites tested). Specifically, 76% of associations were attributable to ethnic differences in cell composition with fewer effects attributable to smoking and genetic variation. Ethnicity associated CpG sites were enriched for EWAS Catalog phenotypes including metabolites. This work highlights the need to consider ethnic diversity in epigenetic research.</jats:p>
Wielgoszewska B, Maddock J, Green MJ, et al., 2022, The UK Coronavirus Job Retention Scheme and diet, physical activity, and sleep during the COVID-19 pandemic: evidence from eight longitudinal population surveys, BMC MEDICINE, Vol: 20, ISSN: 1741-7015
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- Citations: 2
Webber M, Falconer D, AlFarih M, et al., 2022, Study protocol: MyoFit46-the cardiac sub-study of the MRC National Survey of Health and Development, BMC CARDIOVASCULAR DISORDERS, Vol: 22, ISSN: 1471-2261
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- Citations: 2
Anbar R, Sultan SR, Al Saikhan L, et al., 2022, Is carotid artery atherosclerosis associated with poor cognitive function assessed using the Mini-Mental State Examination? A systematic review and meta-analysis, BMJ OPEN, Vol: 12, ISSN: 2044-6055
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- Citations: 2
Palombo C, Kozakova M, Morizzo C, et al., 2022, Carotid Reservoir Pressure Decrease After Prolonged Head Down Tilt Bed Rest in Young Healthy Subjects Is Associated With Reduction in Left Ventricular Ejection Time and Diastolic Length, FRONTIERS IN PHYSIOLOGY, Vol: 13
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- Citations: 2
Schmidt AF, Joshi R, Gordillo-Marañón M, et al., 2022, Biomedical consequences of elevated cholesterol-containing lipoproteins and apolipoproteins
<jats:title>Abstract</jats:title><jats:sec><jats:title>Aims</jats:title><jats:p>To provide a comprehensive evaluation of the biomedical effects of circulating concentrations of cholesterol-containing lipoproteins and apolipoproteins.</jats:p></jats:sec><jats:sec><jats:title>Methods and Results</jats:title><jats:p>Nuclear magnetic resonance (NMR) spectroscopy was used to measure the cholesterol content of high density (HDL-C), very low-density (VLDL-C), intermediate-density (IDL-C), and low-density (LDL-C) lipoprotein fractions; apolipoproteins Apo-A1 and Apo-B; as well as total triglycerides (TG), remnant-cholesterol (Rem-chol) and total cholesterol (TC). The causal effects of these exposures were assessed against 33 cardiovascular as well as non-cardiovascular outcomes using two-sample univariable and multivariable Mendelian randomization. We observed that most cholesterol containing lipoproteins and apolipoproteins affected coronary heart disease (CHD), cIMT, carotid plaque, CRP and blood pressure. Through MVMR we showed that many of these exposures acted independently of the more commonly measured blood lipids: HDL-C, LDL-C and TG. We furthermore found that HF risk was increased by higher concentrations of TG, VLDL-C, Rem-Chol and Apo-B, often independently of LDL-C, HDL-C or TG. Finally, a smaller subset of these exposures could be robustly mapped to non-CVD traits such as Alzheimer’s disease (HDL-C, LDL-C, IDL-C, Apo-B), type 2 diabetes (VLDL-C, IDL-C, LDL-C), and inflammatory bowel disease (LDL-C, IDL-C).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The cholesterol content of a wide range of lipoprotein and apolipoproteins affected measures of atherosclerosis and CHD, implicating subfractions beyond LDL-C. Many of the observed effects acted independently of LDL-C, HDL-C, and TG, supporting the potential for additional, no
Astbury S, Reynolds CJ, Butler DK, et al., 2022, HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19, Immunology, Vol: 166, Pages: 68-77, ISSN: 0019-2805
SARS-CoV-2 infection results in different outcomes ranging from asymptomatic infection to mild or severe disease and death. Reasons for this diversity of outcome include differences in challenge dose, age, gender, comorbidity and host genomic variation. Human leukocyte antigen (HLA) polymorphisms may influence immune response and disease outcome. We investigated the association of HLAII alleles with case definition symptomatic COVID-19, virus-specific antibody and T-cell immunity. A total of 1364 UK healthcare workers (HCWs) were recruited during the first UK SARS-CoV-2 wave and analysed longitudinally, encompassing regular PCR screening for infection, symptom reporting, imputation of HLAII genotype and analysis for antibody and T-cell responses to nucleoprotein (N) and spike (S). Of 272 (20%) HCW who seroconverted, the presence of HLA-DRB1*13:02 was associated with a 6·7-fold increased risk of case definition symptomatic COVID-19. In terms of immune responsiveness, HLA-DRB1*15:02 was associated with lower nucleocapsid T-cell responses. There was no association between DRB1 alleles and anti-spike antibody titres after two COVID vaccine doses. However, HLA DRB1*15:01 was associated with increased spike T-cell responses following both first and second dose vaccination. Trial registration: NCT04318314 and ISRCTN15677965.
Fatih N, Chaturvedi N, Lane CA, et al., 2022, Sex-related differences in whole brain volumes at age 70 in association with hyperglycemia during adult life, Neurobiology of Aging, Vol: 112, Pages: 161-169, ISSN: 0197-4580
Longitudinal studies of the relationship between hyperglycemia and brain health are rare and there is limited information on sex differences in associations. We investigated whether glycosylated hemoglobin (HbA1c) measured at ages of 53, 60–64 and 69 years, and cumulative glycemic index (CGI), a measure of cumulative glycemic burden, were associated with metrics of brain health in later life.Participants were from Insight 46, a substudy of the Medical Research Council National Survey of Health and Development (NSHD) who undertook volumetric MRI, florbetapir amyloid-PET imaging and cognitive assessments at ages of 69–71. Analyses were performed using linear and logistic regression as appropriate, with adjustment for potential confounders. We observed a sex interaction between HbA1c and whole brain volume (WBV) at all 3 time points. Following stratification of our sample, we observed that HbA1c at all ages, and CGI were positively associated with lower WBV exclusively in females. HbA1c (or CGI) was not associated with amyloid status, white matter hyperintensities (WMHs), hippocampal volumes (HV) or cognitive outcomes in either sex.Higher HbA1c in adulthood is associated with smaller WBV at 69–71 years in females but not in males. This suggests that there may be preferential target organ damage in the brain for females with hyperglycemia.
Chiesa ST, Charakida M, Georgiopoulos G, et al., 2022, Glycoprotein Acetyls: A Novel Inflammatory Biomarker of Early Cardiovascular Risk in the Young, JOURNAL OF THE AMERICAN HEART ASSOCIATION, Vol: 11
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- Citations: 16
Gu B, Huang Y, Manchester E, et al., 2022, Multiphysics modelling and simulation of thrombolysis via activated platelet-targeted nanomedicine, Pharmaceutical Research, Vol: 39, Pages: 41-56, ISSN: 0724-8741
Purpose:This study establishes a multiphysics simulation platform for both conventional and targeted thrombolysis using tissue plasminogen activator (tPA). Based on our computational results, the effects of therapeutic parameters on the dynamics of thrombolysis and the risk of side effects are investigated.Methods:The model extends our previously developed one-dimensional(1D) mathematical models for fibrinolysis by incorporating targeted thrombolysis. It consists of two parts: (i) a coupled mathematical model of systemic pharmacokinetics (PK) and pharmacodynamics (PD) and local PD in a 1D occluded artery, and (ii) a mechanistic model for a targeted thrombolytic system via activated platelet-targeted tPA-loaded nanovesicles (tPA-NV), with model parameters derived from our in vitro experiments. A total of 16 therapeutic scenarios are simulated by varying the clot location and composition as well as the dosing regimen with free tPA or tPA-NV.Results:Our simulation results indicate that tPA-NV offers several advantages over free tPA for thrombolysis. It reduces systemic exposure of tPA, thereby minimising the risk of bleeding complications. Simulations with different tPA-NV doses reveal that tPA-NV at 10% of the recommended dose can be as effective as the standard regimen with the full recommended dose of free tPA, demonstrating the potential of our tPA-NV as a new thrombolytic strategy with a reduced tPA dose. Moreover, faster recanalisation can be achieved with tPA-NV, especially for platelet-rich(or fibrin-poor) clots.Conclusions:Our simulation platform for thrombolysis with well-tuned model parameters can be used to evaluate and optimise treatment regimens of existing and new thrombolytic therapies via benefit/risk assessment under various therapeutic scenarios.
Hughes AD, Eastwood SV, Tillin T, et al., 2022, Antihypertensive Medication Use and Its Effects on Blood Pressure and Haemodynamics in a Tri-ethnic Population Cohort: Southall and Brent Revisited (SABRE), FRONTIERS IN CARDIOVASCULAR MEDICINE, Vol: 8, ISSN: 2297-055X
Orini M, Guvensen G, Jamieson A, et al., 2022, Movement, Sweating, and Contact Pressure as Sources of Heart Rate Inaccuracy in Wearable Devices, ISSN: 2325-8861
Wearable devices enable continuous heart rate (HR) monitoring through photoplethysmography (PPG). The impact of wrist-worn devices' sensor contact pressure and sweat, and of their interaction with movement, on HR monitoring is unclear. HR was recorded in 17 healthy individuals using two smartwatches, Garmin Vivoactive 4 (GV) and Fitbit Sense (FS), concurrently with ECG at rest and during controlled arm movement at three increasing intensities. Recordings were repeated after reducing contact pressure by loosening the wristband by one or two notches and using one or two drops of saline solution to simulate sweating. In optimal conditions, the mean absolute percentage error (MAPE) was (median [interquartile range]) 4.3% (1.4%, 7.7%) and 3.1% (1.6%, 5.0%) (p=0.58), for GV and FS, respectively. Loosening the wristband by 1 notch increased MAPE for FS during rest (p=0.021), moderate (p=0.004) and vigorous (p=0.002) movement, but not for GV, for which loosening the wristband by 2 notches increased MAPE during moderate (p=0. 015) and vigorous (p=0.008) movement. Simulated sweat increased MAPE during moderate movement using FS (p=0.002), and during vigorous movement for both devices. In conclusion, contact pressure and sweating can increase HR inaccuracy even during rest and moderate movement.
Jamieson A, Orini M, Chaturvedi N, et al., 2022, A Validation Study of Two Wrist Worn Wearable Devices for Remote Assessment of Exercise Capacity, ISSN: 2325-8861
We determined wearable device errors in assessing a 6-Minute Walk Test (6MWT). 16 healthy adults (male 7(44%), mean age ± SD 27 ± 4 years) performed a standard (6MWT-S) and modified, free range', (6MWT-FR) protocols with a Garmin and Fitbit smartwatch to measure three parameters: distance, step count and heart rate (HR). Distance during the 6MWT-FR was measured with smaller errors during 6MWT-S for both Garmin (Mean Absolute Percentage Error, MAPE=9.8% [4.6%,12.6%] vs 18.5%[13.0%,27.4%],p < 0.001) and Fitbit (MAPE=9.4%[4.5%, 13.3%] vs 22.7%[18.3%, 29.3%],p < 0.001). Steps were measured with smaller errors with Garmin (MAPE=2.3%[1.1%, 2.9%]; r=0.96) than Fitbit (Fitbit: MAPE=8.1%[5.0%,12.9%]; r=0.24). Heart rate at rest, peak exercise and recovery was measured with median MAPE ranging between 1.2% and 2.9%, with no evidence of difference between the two devices. Wearable measurements of the 6MWT provide insights about exercise capacity which could be monitored and evaluated remotely.
Orini M, Guvensen G, Jamieson A, et al., 2022, Movement, Sweating, and Contact Pressure as Sources of Heart Rate Inaccuracy in Wearable Devices, ISSN: 2325-8861
Wearable devices enable continuous heart rate (HR) monitoring through photoplethysmography (PPG). The impact of wrist-worn devices' sensor contact pressure and sweat, and of their interaction with movement, on HR monitoring is unclear. HR was recorded in 17 healthy individuals using two smartwatches, Garmin Vivoactive 4 (GV) and Fitbit Sense (FS), concurrently with ECG at rest and during controlled arm movement at three increasing intensities. Recordings were repeated after reducing contact pressure by loosening the wristband by one or two notches and using one or two drops of saline solution to simulate sweating. In optimal conditions, the mean absolute percentage error (MAPE) was (median [interquartile range]) 4.3% (1.4%, 7.7%) and 3.1% (1.6%, 5.0%) (p=0.58), for GV and FS, respectively. Loosening the wristband by 1 notch increased MAPE for FS during rest (p=0.021), moderate (p=0.004) and vigorous (p=0.002) movement, but not for GV, for which loosening the wristband by 2 notches increased MAPE during moderate (p=0.015) and vigorous (p=0.008) movement. Simulated sweat increased MAPE during moderate movement using FS(p=0.002), and during vigorous movement for both devices. In conclusion, contact pressure and sweating can increase HR inaccuracy even during rest and moderate movement.
Patel KP, Scully PR, Nitsche C, et al., 2022, Impact of afterload and infiltration on coexisting aortic stenosis and transthyretin amyloidosis, HEART, Vol: 108, Pages: 67-72, ISSN: 1355-6037
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- Citations: 5
Farmaki A-E, Garfield V, Eastwood SV, et al., 2022, Type 2 diabetes risks and determinants in second-generation migrants and mixed ethnicity people of South Asian and African Caribbean descent in the UK, DIABETOLOGIA, Vol: 65, Pages: 113-127, ISSN: 0012-186X
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- Citations: 2
Sutton E, Early J, Hughes A, et al., 2021, NRF2/KEAP1 pathway is required to fine-tune circadian oscillations as part of the negative feedback loop of the molecular clock: implications for tissue homeostasis and therapeutic interventions, Annual Meeting of the Society-for-Free-Radical-Research-Europe (SFRR-E) - Redox Biology in the 21st Century - A New Scientific Discipline, Publisher: ELSEVIER SCIENCE INC, ISSN: 0891-5849
Bann D, Villadsen A, Maddock J, et al., 2021, Changes in the behavioural determinants of health during the COVID-19 pandemic: gender, socioeconomic and ethnic inequalities in five British cohort studies, JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH, Vol: 75, Pages: 1136-1142, ISSN: 0143-005X
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- Citations: 45
Webber M, Joy G, Falconer D, et al., 2021, Non-Invasive Electrocardiographic Mapping of the Human Heart Through a Novel 'Cardiac Magnetic Resonance-Electrocardiographic Imaging' Solution for High Throughput Use, Annual Scientific Sessions of the American-Heart-Association / Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322
Wels J, Booth C, Wielgoszewska B, et al., 2021, Mental and social wellbeing and the UK Coronavirus Job Retention Scheme: evidence from nine longitudinal studies
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The COVID-19 pandemic has led to major economic disruptions. In March 2020, the UK implemented the Coronavirus Job Retention Scheme – known as furlough – to minimize the impact of job losses. We investigate associations between change in employment status and mental and social wellbeing during the early stages of the pandemic.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Data were from 25,670 respondents, aged 17 to 66, across nine UK longitudinal studies. Furlough and other employment changes were defined using employment status pre-pandemic and during the first lockdown (April-June 2020). Mental and social wellbeing outcomes included psychological distress, life satisfaction, self-rated health, social contact, and loneliness. Study-specific modified Poisson regression estimates, adjusting for socio-demographic characteristics and pre-pandemic mental and social wellbeing measures, were pooled using meta-analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Compared to those who remained working, furloughed workers were at greater risk of psychological distress (adjusted risk ratio, ARR=1.12; 95% CI: 0.97, 1.29), low life satisfaction (ARR=1.14; 95% CI: 1.07, 1.22), loneliness (ARR=1.12; 95% CI: 1.01, 1.23), and poor self-rated health (ARR=1.26; 95% CI: 1.05, 1.50), but excess risk was less pronounced than that of those no longer employed (e.g., ARR for psychological distress=1.39; 95% CI: 1.21, 1.59) or in stable unemployment (ARR=1.33; 95% CI: 1.09, 1.62).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>During the early stages of the pandemic, those furloughed had increased risk for poor mental and social wellbeing. However, their excess risk was lower i
Swadling L, Diniz MO, Schmidt NM, et al., 2021, Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2, Nature, Vol: 601, Pages: 110-117, ISSN: 0028-0836
Individuals with potential exposure to SARS-CoV-2 do not necessarily develop PCR or antibody positivity, suggesting some may clear sub-clinical infection before seroconversion. T-cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections1-3. We hypothesised that pre-existing memory T-cell responses, with cross-protective potential against SARS-CoV-24-11, would expand in vivo to support rapid viral control, aborting infection. We measured SARS-CoV-2-reactive T-cells, including those against the early transcribed replication transcription complex (RTC)12,13, in intensively monitored healthcare workers (HCW) remaining repeatedly negative by PCR, antibody binding, and neutralisation (seronegative HCW, SN-HCW). SN-HCW had stronger, more multispecific memory T-cells than an unexposed pre-pandemic cohort, and more frequently directed against the RTC than the structural protein-dominated responses seen post-detectable infection (matched concurrent cohort). SN-HCW with the strongest RTC-specific T-cells had an increase in IFI27, a robust early innate signature of SARS-CoV-214, suggesting abortive infection. RNA-polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and SARS-CoV-2 clades. RNA-polymerase was preferentially targeted (amongst regions tested) by T-cells from pre-pandemic cohorts and SN-HCW. RTC epitope-specific T-cells cross-recognising HCoV variants were identified in SN-HCW. Enriched pre-existing RNA-polymerase-specific T-cells expanded in vivo to preferentially accumulate in the memory response after putative abortive compared to overt SARS-CoV-2 infection. Our data highlight RTC-specific T-cells as targets for vaccines against endemic and emerging Coronaviridae.
Al Saikhan L, Alobaida M, Bhuva A, et al., 2021, Imaging Protocol, Feasibility, and Reproducibility of Cardiovascular Phenotyping in a Large Tri-Ethnic Population-Based Study of Older People: The Southall and Brent Revisited (SABRE) Study (vol 7,591946,2020), FRONTIERS IN CARDIOVASCULAR MEDICINE, Vol: 8, ISSN: 2297-055X
Green MJ, Maddock J, Di Gessa G, et al., 2021, The UK COVID-19 furlough scheme and associations with smoking, alcohol consumption and vaping: evidence from 8 UK longitudinal population surveys
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Disruptions to employment status can impact smoking and alcohol consumption. During the COVID-19 pandemic, the UK implemented a furlough scheme to prevent job loss. We examine how furlough was associated with participants’ smoking, vaping and alcohol consumption behaviours in the early stages of the pandemic.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Data were from 27,841 participants in eight UK adult longitudinal surveys. Participants self-reported employment status and current smoking, current vaping and drinking alcohol (>4 days/week or 5+ drinks per typical occasion) both before and during the pandemic (April-July 2020). Risk ratios were estimated within each study using modified Poisson regression, adjusting for a range of potential confounders, including pre-pandemic behaviour. Findings were synthesised using random effects meta-analysis. Sub-group analyses were used to identify whether associations differed by gender, age or education.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Compared to stable employment, neither furlough, no longer being employed, nor stable unemployment were associated with smoking, vaping or drinking, following adjustment for pre-pandemic characteristics. However, some sex differences in these associations were observed, with stable unemployment associated with smoking for women (ARR=1.35; 95% CI: 1.00-1.82; I<jats:sup>2</jats:sup>: 47%) but not men (0.84; 95% CI: 0.67-1.05; I<jats:sup>2</jats:sup>: 0%). No longer being employed was associated with vaping among women (ARR=2.74; 95% CI: 1.59-4.72; I<jats:sup>2</jats:sup>: 0%) but not men (ARR=1.25; 95% CI: 0.83-1.87; I<jats:sup>2</jats:sup>: 0%). There was little indication of associa
Seraphim A, Knott KD, Menacho K, et al., 2021, Prognostic Value of Pulmonary Transit Time and Pulmonary Blood Volume Estimation Using Myocardial Perfusion CMR, JACC-CARDIOVASCULAR IMAGING, Vol: 14, Pages: 2107-2119, ISSN: 1936-878X
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- Citations: 11
Webber M, Joy G, Falconer D, et al., 2021, MYOCARDIAL INFLAMMATION AND DIFFUSE FIBROSIS UNDERPIN THE ELECTROPHYSIOLOGICAL DERANGEMENTS OF THE AGEING HUMAN HEART-A CMR-ECGI STUDY, Annual Meeting of the British-Society-of-Cardiovascular-Magnetic-Resonance (BSCMR), Publisher: BMJ PUBLISHING GROUP, Pages: A10-A11, ISSN: 1355-6037
Fornasiero M, Pierce I, Webber M, et al., 2021, A MEDICAL DEVICE-GRADE T2 PHANTOM FOR QUALITY ASSURANCE OF INFLAMMATION IMAGING BY CMR, Annual Meeting of the British-Society-of-Cardiovascular-Magnetic-Resonance (BSCMR), Publisher: BMJ PUBLISHING GROUP, Pages: A9-A10, ISSN: 1355-6037
Gordillo-Maranon M, Zwierzyna M, Charoen P, et al., 2021, Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics, NATURE COMMUNICATIONS, Vol: 12
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- Citations: 3
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