Imperial College London

Prof Liz Lightstone

Faculty of MedicineDepartment of Immunology and Inflammation

Proconsul and Professor of Renal Medicine
 
 
 
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Contact

 

+44 (0)20 3313 3152l.lightstone Website CV

 
 
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Assistant

 

Miss Anjli Jagpal +44 (0)20 3313 3152

 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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222 results found

Svetitsky S, Lightstone L, Wiles K, 2023, Pregnancy in women with nephrotic-range proteinuria: A retrospective cohort study, OBSTETRIC MEDICINE, ISSN: 1753-495X

Journal article

Pearce FA, Lim SH, Bythell M, Lanyon P, Hogg R, Taylor A, Powter G, Cooke GS, Ward H, Chilcot J, Thomas H, Mumford L, McAdoo SP, Pettigrew GJ, Lightstone L, Willicombe Met al., 2023, Antibody prevalence after three or more COVID-19 vaccine doses in individuals who are immunosuppressed in the UK: a cross-sectional study from MELODY, The Lancet Rheumatology, Vol: 5, Pages: e461-e473, ISSN: 2665-9913

BackgroundIn the UK, additional COVID-19 vaccine booster doses and treatments are offered to people who are immunosuppressed to protect against severe COVID-19, but how best to choose the individuals that receive these vaccine booster doses and treatments is unclear. We investigated the association between seropositivity to SARS-CoV-2 spike protein with demographic, disease, and treatment-related characteristics after at least three COVID-19 vaccines in three cohorts of people who are immunosuppressed.MethodsIn a cross-sectional study using UK national disease registries, we identified, contacted, and recruited recipients of solid organ transplants, participants with rare autoimmune rheumatic diseases, and participants with lymphoid malignancies who were 18 years or older, resident in the UK, and who had received at least three doses of a COVID-19 vaccine. The study was open to recruitment from Dec 7, 2021, to June 26, 2022. Participants received a lateral flow immunoassay test for SARS-CoV-2 spike antibodies to complete at home, and an online questionnaire. Multivariable logistic regression was used to estimate the mutually adjusted odds of seropositivity against each characteristic.FindingsBetween Feb 14 and June 26, 2022, we screened 101 972 people (98 725 invited, 3247 self-enrolled) and recruited 28 411 (27·9%) to the study. 23 036 (81·1%) recruited individuals provided serological data. Of these, 9927 (43·1%) were recipients of solid organ transplants, 6516 (28·3%) had rare autoimmune rheumatic diseases, and 6593 (28·6%) had lymphoid malignancies. 10 485 (45·5%) participants were men and 12 535 (54·4%) were women (gender was not reported for 16 [<0·1%] participants), and 21661 (94·0%) participants were of White ethnicity. The median age of participants with solid organ transplants was 60 years (SD 50–67), with rare autoimmune rheumatic diseases was

Journal article

Jackson C, Stewart ID, Plekhanova T, Cunningham PS, Hazel AL, Al-Sheklly B, Aul R, Bolton CE, Chalder T, Chalmers JD, Chaudhuri N, Docherty AB, Donaldson G, Edwardson CL, Elneima O, Greening NJ, Hanley NA, Harris VC, Harrison EM, Ho L-P, Houchen-Wolloff L, Howard LS, Jolley CJ, Jones MG, Leavy OC, Lewis KE, Lone NI, Marks M, McAuley HJC, McNarry MA, Patel BV, Piper-Hanley K, Poinasamy K, Raman B, Richardson M, Rivera-Ortega P, Rowland-Jones SL, Rowlands AV, Saunders RM, Scott JT, Sereno M, Shah AM, Shikotra A, Singapuri A, Stanel SC, Thorpe M, Wootton DG, Yates T, Gisli Jenkins R, Singh SJ, Man WD-C, Brightling CE, Wain LV, Porter JC, Thompson AAR, Horsley A, Molyneaux PL, Evans RA, Jones SE, Rutter MK, Blaikley JF, PHOSP-COVID Study Collaborative Groupet al., 2023, Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study, The Lancet Respiratory Medicine, Vol: 11, Pages: 673-684, ISSN: 2213-2600

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended

Journal article

Anders H-J, Furie R, Malvar A, Zhao M-H, Hiromura K, Weinmann-Menke J, Green Y, Jones-Leone A, Negrini D, Levy RA, Lightstone L, Tanaka Y, Rovin BHet al., 2023, Effect of belimumab on kidney-related outcomes in patients with lupus nephritis: post hoc subgroup analyses of the phase 3 BLISS-LN trial., Nephrol Dial Transplant

BACKGROUND: Data on belimumab efficacy in patients with lupus nephritis (LN) according to diagnosis duration or induction therapy are limited. Post hoc analyses of the Phase 3, randomized, double-blind BLISS-LN study were performed to assess belimumab efficacy on kidney-related outcomes in newly diagnosed and relapsed LN subgroups, and according to use of glucocorticoid pulses at induction. METHODS: BLISS-LN (GSK BEL114054; NCT01639339) randomized 448 patients with active LN to monthly intravenous belimumab 10 mg/kg or placebo plus standard therapy. Post hoc analyses assessed Primary Efficacy Renal Response (PERR) and Complete Renal Response (CRR) at Week 104, time to kidney-related event or death, and time to first LN flare from Week 24 in newly diagnosed and relapsed patients, and patients with/without glucocorticoid pulses at induction. RESULTS: A greater proportion of patients achieved PERR with belimumab versus placebo in the newly diagnosed (69/148 [46.6%] vs 55/148 [37.2%]; odds ratio, OR [95% confidence interval, CI] 1.36 [0.85, 2.20]) and relapsed (27/75 [36.0%] vs 17/75 [22.7%]; 2.31 [1.07, 5.01]) subgroups. Similarly for CRR (newly diagnosed: 50/148 [33.8%] vs 36/148 [24.3%]; OR 1.49 [95% CI 0.88, 2.51] and relapsed: 17/75 [22.7%] vs 8/75 [10.7%]; 3.11 [1.16, 8.31]). Probability of kidney-related event or death, or LN flare, was lower with belimumab versus placebo in both subgroups. Belimumab was associated with improved kidney outcomes versus placebo with or without glucocorticoid pulses at induction. CONCLUSIONS: Data suggest consistent benefits of belimumab on kidney outcomes for newly diagnosed and relapsed patients, and irrespective of glucocorticoid pulses at induction.

Journal article

Barnes E, Goodyear CS, Willicombe M, Gaskell C, Siebert S, I de Silva T, Murray SM, Rea D, Snowden JA, Carroll M, Pirrie S, Bowden SJ, Dunachie SJ, Richter A, Lim Z, Satsangi J, Cook G, Pope A, Hughes A, Harrison M, Lim SH, Miller P, Klenerman P, Richter AG, Mentzer A, Deeks A, Jamsen A, Brown A, Conlon C, Dold C, Duncan CJA, Skelly D, Kronsteiner B, Abraham P, Phillips E, Jeffery K, Turtle L, Frending L, Stafford L, Ali M, Rongkard P, Payne R, Adele S, Travis S, Gardiner S, Dobson SL, Malone T, Bibi S, Carroll M, Faustini S, Foulkes S, Frater J, Hall V, Hopkins S, Islam J, Lambe T, Longet S, Moore SC, Otter A, Rowland-Jones SL, Thaventhir JED, Wootton DG, Basu N, Gilmour A, Irwin S, Meacham G, Marjot T, Dimitriadis S, Kelleher P, Prendecki M, Clarke C, Mortimer P, McIntyre S, Selby R, Meardon N, Nguyen D, Tipton T, Longet S, Laidlaw S, Orchard K, Ireland G, Brown K, Amirthalingam G, Thomas D, Kearns P, Kirkham A, McInnes IB, Beesley R, Churchill V, Loughton H, Insch E, MacDonald E, Middleton G, Billingham L, Lowe F, Magwaro S, Al-Taei S, Arnott M, Bennett L, Brock J, Keillor V, Melville A, Melville L, Miller S, Najm A, Paterson C, Rodgers L, Rutherford M, Rundell S, Smith E, Stewart L, Sunzini F, Tong A, Woolcock K, Basheer F, Crawley C, Malladi R, King A, Lockey S, Uttenthal B, Koh MBC, Hansford S, Sandhar G, Kesavan M, Moore C, Manousou P, Hahn G, Mullish B, Atta M, Gleeson S, Lightstone L, Martin P, McAdoo S, Thomson T, Avenoso D, Sanderson R, Taylor C, Bhandal K, Hull D, Trivedi P, Filer A, Hurst E, Publicover A, Scouse K, Chalk J, Hanke D, Hanke J, Healy S, Provine N, Thomas S, Walker V, Win Z, Trown D, Faria P, Chackathayil J, Hutchison C, Richardson D, PITCH consortium, CONSENSUS, OCTAVE Collaborative Groupet al., 2023, SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease, Nature Medicine, ISSN: 1546-170X

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml−1). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies.

Journal article

Zheng B, Vivaldi G, Daines L, Leavy OC, Richardson M, Elneima O, McAuley HJC, Shikotra A, Singapuri A, Sereno M, Saunders RM, Harris VC, Houchen-Wolloff L, Greening NJ, Pfeffer PE, Hurst JR, Brown JS, Shankar-Hari M, Echevarria C, De Soyza A, Harrison EM, Docherty AB, Lone N, Quint JK, Chalmers JD, Ho L-P, Horsley A, Marks M, Poinasamy K, Raman B, Heaney LG, Wain LV, Evans RA, Brightling CE, Martineau A, Sheikh A, Abel K, Adamali H, Adeloye D, Adeyemi O, Adrego R, Aguilar Jimenez LA, Ahmad S, Ahmad Haider N, Ahmed R, Ahwireng N, Ainsworth M, Al-Sheklly B, Alamoudi A, Ali M, Aljaroof M, All AM, Allan L, Allen RJ, Allerton L, Allsop L, Almeida P, Altmann D, Alvarez Corral M, Amoils S, Anderson D, Antoniades C, Arbane G, Arias A, Armour C, Armstrong L, Armstrong N, Arnold D, Arnold H, Ashish A, Ashworth A, Ashworth M, Aslani S, Assefa-Kebede H, Atkin C, Atkin P, Aul R, Aung H, Austin L, Avram C, Ayoub A, Babores M, Baggott R, Bagshaw J, Baguley D, Bailey L, Baillie JK, Bain S, Bakali M, Bakau M, Baldry E, Baldwin D, Baldwin M, Ballard C, Banerjee A, Bang B, Barker RE, Barman L, Barratt S, Barrett F, Basire D, Basu N, Bates M, Bates A, Batterham R, Baxendale H, Bayes H, Beadsworth M, Beckett P, Beggs M, Begum M, Beirne P, Bell D, Bell R, Bennett K, Beranova E, Bermperi A, Berridge A, Berry C, Betts S, Bevan E, Bhui K, Bingham M, Birchall K, Bishop L, Bisnauthsing K, Blaikely J, Bloss A, Bolger A, Bolton CE, Bonnington J, Botkai A, Bourne C, Bourne M, Bramham K, Brear L, Breen G, Breeze J, Briggs A, Bright E, Brightling CE, Brill S, Brindle K, Broad L, Broadley A, Brookes C, Broome M, Brown A, Brown J, Brown JS, Brown M, Brown V, Brugha T, Brunskill N, Buch M, Buckley P, Bularga A, Bullmore E, Burden L, Burdett T, Burn D, Burns G, Burns A, Busby J, Butcher R, Butt A, Byrne S, Cairns P, Calder PC, Calvelo E, Carborn H, Card B, Carr C, Carr L, Carson G, Carter P, Casey A, Cassar M, Cavanagh J, Chablani M, Chalder T, Chalmers JD, Chambers RC, Chan F, Channon KM, Chapman Ket al., 2023, Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls, The Lancet Regional Health. Europe, Vol: 29, Pages: 1-13, ISSN: 2666-7762

BackgroundThe risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea.MethodsWe used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up.FindingsWe included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission).InterpretationFactors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19.FundingPHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publica

Journal article

Bajema IM, Balow JE, Haas M, Jayne D, Lightstone L, Rovin BH, V Seshan S, Fogo ABet al., 2023, Update on scoring and providing evidence basis for assessing pathology in lupus nephritis, KIDNEY INTERNATIONAL, Vol: 103, Pages: 813-816, ISSN: 0085-2538

Journal article

McAuley HJC, Evans RA, Bolton CE, Brightling CE, Chalmers JD, Docherty AB, Elneima O, Greenhaff PL, Gupta A, Harris VC, Harrison EM, Ho L-P, Horsley A, Houchen-Wolloff L, Jolley CJ, Leavy OC, Lone NI, Man WD-C, Marks M, Parekh D, Poinasamy K, Quint JK, Raman B, Richardson M, Saunders RM, Sereno M, Shikotra A, Singapuri A, Singh SJ, Steiner M, Tan AL, Wain LV, Welch C, Whitney J, Witham MD, Lord J, Greening NJ, PHOSP-COVID Study Collaborative Groupet al., 2023, Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study., EClinicalMedicine, Vol: 57, Pages: 1-13, ISSN: 2589-5370

BACKGROUND: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. METHODS: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group-robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)-at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. FINDINGS: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. INTERPRETATION: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although

Journal article

Nester C, Appel GB, Bomback AS, Bouman KP, Cook HT, Daina E, Dixon BP, Rice K, Najafian N, Hui J, Podos SD, Langman CB, Lightstone L, Parikh S, Pickering MC, Sperati CJ, Trachtman H, Tumlin J, de Vries APJ, Wetzels JFM, Remuzzi Get al., 2023, Clinical Outcomes of Patients with C3G or IC-MPGN Treated with the Factor D Inhibitor Danicopan: Final Results from Two Phase 2 Studies (vol 53, pg 687, 2023), AMERICAN JOURNAL OF NEPHROLOGY, ISSN: 0250-8095

Journal article

Gleeson S, Martin P, Thomson T, Spensley KJ, Goodall D, Bedi R, Thind AK, Seneschall C, Gan J, McAdoo S, Lightstone L, Kelleher P, Prendecki M, Willicombe Met al., 2023, Lack of seroresponse to SARS-CoV-2 booster vaccines given early post-transplant in patients primed pre-transplantation, Frontiers in Immunology, Vol: 13, Pages: 1-10, ISSN: 1664-3224

SARS-CoV-2 vaccines are recommended pre-transplantation, however, waning immunity and evolving variants mandate booster doses. Currently there no data to inform the optimal timing of booster doses post-transplant, in patients primed pre-transplant. We investigated serial serological samples in 204 transplant recipients who received 2 or 3 SARS-CoV-2 vaccines pre-transplant. Spike protein antibody concentrations, [anti-S], were measured on the day of transplantation and following booster doses post-transplant. In infection-naïve patients, post-booster [anti-S] did not change when V3 (1st booster) was given at 116(78-150) days post-transplant, falling from 122(32-574) to 111(34-682) BAU/ml, p=0.78. Similarly, in infection-experienced patients, [anti-S] on Day-0 and post-V3 were 1090(133-3667) and 2207(650-5618) BAU/ml respectively, p=0.26. In patients remaining infection-naïve, [anti-S] increased post-V4 (as 2nd booster) when given at 226(208-295) days post-transplant, rising from 97(34-1074) to 5134(229-5680) BAU/ml, p=0.0016. Whilst in patients who had 3 vaccines pre-transplant, who received V4 (as 1st booster) at 82(49-101) days post-transplant, [anti-S] did not change, falling from 981(396-2666) to 871(242-2092) BAU/ml, p=0.62. Overall, infection pre-transplant and [anti-S] at the time of transplantation predicted post-transplant infection risk. As [Anti-S] fail to respond to SARS-CoV-2 booster vaccines given early post-transplant, passive immunity may be beneficial to protect patients during this period.

Journal article

Wong E, Nester C, Cavero T, Karras A, Le Quintrec M, Lightstone L, Eisenberger U, Soler MJ, Kavanagh D, Daina E, Praga M, Medjeral-Thomas NR, G├Ąckler A, Garcia-Carro C, Biondani A, Chaperon F, Kulmatycki K, Milojevic J, Webb NJA, Nidamarthy PK, Junge G, Remuzzi Get al., 2023, Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy, Kidney International Reports, ISSN: 2468-0249

Introduction: Complement 3 glomerulopathy (C3G) is a rare inflammatory kidney disease mediated by dysregulation of the alternative complement pathway. No targeted therapy exists for this aggressive glomerulonephritis. Efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) (measured by complement biomarkers) of iptacopan were assessed in patients with C3G. Methods: In this phase 2, multicenter, open-label, single-arm, nonrandomized study, adults with biopsy-proven, native kidney C3G (native cohort) and kidney transplant recipients with C3G recurrence (recurrent kidney transplant [KT] cohort) received iptacopan twice daily (bid) for 84 days (days 1–21: 10–100 mg; days 22–84: 200 mg). The primary end point was the urine protein-to-creatinine ratio (UPCR; native cohort) and the change in the C3 deposit score of kidney biopsy (recurrent KT cohort). The complement pathway measures included Wieslab assay, soluble C5b9, and serum C3 levels. Results: A total of 27 patients (16 native cohort and 11 recurrent KT cohort) were enrolled and all completed the study. In the native cohort, UPCR levels decreased by 45% from baseline to week 12 (P = 0.0003). In the recurrent KT cohort, the median C3 deposit score decreased by 2.50 (scale: 0–12) on day 84 versus baseline (P = 0.03). Serum C3 levels were normalized in most patients; complement hyperactivity observed pretreatment was reduced. Severe adverse events (AEs) included post-biopsy hematuria and hyperkalemia. No deaths occurred during the study. Conclusion: Iptacopan resulted in statistically significant and clinically important reductions in UPCR and normalization of serum C3 levels in the native cohort and reduced C3 deposit scores in the recurrent KT cohort with favorable safety and tolerability. (ClinicalTrials.gov identifier: NCT03832114).

Journal article

Nester C, Appel GB, Bomback AS, Bouman KP, Cook HT, Daina E, Dixon BP, Rice K, Najafian N, Hui J, Podosh SD, Langman CB, Lightstone L, Parikh SV, Pickering MC, Sperati CJ, Trachtman H, Tumlin J, de Vries APJ, Wetzels JFM, Remuzzi Get al., 2023, Clinical Outcomes of Patients with C3G or IC-MPGN Treated with the Factor D Inhibitor Danicopan: Final Results from Two Phase 2 Studies, AMERICAN JOURNAL OF NEPHROLOGY, Vol: 53, Pages: 687-700, ISSN: 0250-8095

Journal article

Podos SD, Trachtman H, Appel GB, Bomback AS, Dixon BP, Wetzels JFM, Cook HT, Parikh SV, Pickering MC, Tumlin J, Langman CB, Lightstone L, Sperati CJ, Daina E, Bouman KP, Rice K, Thanassi JA, Huang M, Nester C, Remuzzi Get al., 2023, Baseline Clinical Characteristics and Complement Biomarkers of Patients with C3 Glomerulopathy Enrolled in Two Phase 2 Studies Investigating the Factor D Inhibitor Danicopan, AMERICAN JOURNAL OF NEPHROLOGY, Vol: 53, Pages: 675-686, ISSN: 0250-8095

Journal article

Liew F, Talwar S, Cross A, Willett B, Scott S, Logan N, Siggins M, Swieboda D, Sidhu J, Efstathiou C, Moore S, Davis C, Mohamed N, Nunag J, King C, Thompson AAR, Rowland-Jones S, Docherty A, Chalmers J, Ho L-P, Horsley A, Raman B, Poinasamy K, Marks M, Kon OM, Howard L, Wootton D, Dunachie S, Quint J, Evans R, Wain L, Fontanella S, de Silva T, Ho A, Harrison E, Baillie JK, Semple MG, Brightling C, Thwaites R, Turtle L, Openshaw Pet al., 2023, SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination, EBioMedicine, Vol: 87, Pages: 1-14, ISSN: 2352-3964

Background:Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.Methods:In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data.Findings:Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.Interpretation:The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.Funding:This

Journal article

Thomson T, Prendecki M, Gleeson S, Martin P, Spensley K, De Aguiar RC, Sandhu B, Seneschall C, Gan J, Clarke CL, Lewis S, Pickard G, Thomas D, McAdoo SP, Lightstone L, Cox A, Kelleher P, Willicombe Met al., 2022, Immune responses following 3rd and 4th doses of heterologous and homologous COVID-19 vaccines in kidney transplant recipients, eClinicalMedicine, Vol: 53, Pages: 1-9, ISSN: 2589-5370

BackgroundSolid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. In this study, we report on immune responses to 3rd- (V3) and 4th- (V4) doses of heterologous and homologous vaccines in a kidney transplant population.MethodsWe undertook a single centre cohort study of 724 kidney transplant recipients prospectively screened for serological responses following 3 primary doses of a SARS-CoV2 vaccine. 322 patients were sampled post-V4 for anti-spike (anti-S), with 69 undergoing assessment of SARS-CoV-2 T-cell responses. All vaccine doses were received post-transplant, only mRNA vaccines were used for V3 and V4 dosing. All participants had serological testing performed post-V2 and at least once prior to their first dose of vaccine.Findings586/724 (80.9%) patients were infection-naïve post-V3; 141/2586 (24.1%) remained seronegative at 31 (21-51) days post-V3. Timing of vaccination in relation to transplantation, OR: 0.28 (0.15-0.54), p=0.0001; immunosuppression burden, OR: 0.22 (0.13-0.37), p<0.0001, and a diagnosis of diabetes, OR: 0.49 (0.32-0.75), p=0.001, remained independent risk factors for non-seroconversion. Seropositive patients post-V3 had greater anti-S if primed with BNT162b2 compared with ChAdOx1, p=0.001.Post-V4, 45/239 (18.8%) infection-naïve patients remained seronegative. De novo seroconversion post-V4 occurred in 15/60 (25.0%) patients. There was no difference in anti-S post-V4 by vaccine combination, p=0.50. T-cell responses were poor, with only 11/54 (20.4%) infection-naive patients having detectable T-cell responses post-V4, with no difference seen by vaccine type.InterpretationA significant proportion of transplant recipients remain seronegative following 3- and 4- doses of SARS-CoV-2 vaccines, with poor T-cell responses, and are likely to have inadequate protection against infection. As such alternative strategies are required to provide protection to this vulnerable group.FundingMW/PK received study

Journal article

Martin P, Gleeson S, Clarke C, Thomson T, Edwards H, Spensley K, Mortimer P, Mcintyre S, cox A, Pickard G, Lightstone E, Thomas D, McAdoo S, kelleher P, Prendecki M, Willicombe Met al., 2022, Comparison of immunogenicity and clinical effectiveness between BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines in people with end-stage kidney disease receiving haemodialysis: a prospective, observational cohort study, The Lancet Regional Health Europe, Vol: 21, ISSN: 2666-7762

Background:People with end-stage kidney disease, including people on haemodialysis, are susceptible to greater COVID-19 related morbidity and mortality. This study compares the immunogenicity and clinical effectiveness of BNT162B2 versus ChAdOx1 in haemodialysis patients.Methods:In this observational cohort study, 1021 patients were followed-up from time of vaccination until December 2021. All patients underwent weekly RT-PCR screening. Patients were assessed for nucleocapsid(anti-NP) and spike(anti-S) antibodies at timepoints after second(V2) and third(V3) vaccinations. 191 patients were investigated for T-cell responses. Vaccine effectiveness (VE) for prevention of infection, hospitalisation and mortality was evaluated using the formula VE=(1-adjustedHR)x100.Findings:45.7% (467/1021) had evidence of prior infection. There was no difference in the proportion of infection-naïve patients who seroconverted by vaccine type, but median anti-S antibody titres were higher post-BNT162b2 compared with ChAdOx1; 462(152-1171) and 78(20-213) BAU/ml respectively, p<0.001. Concomitant immunosuppressant use was a risk factor for non-response, OR 0.12[95% CI 0.05–0.25] p<0.001. Post-V3 (all BNT162b2), median anti-S antibody titres remained higher in those receiving BNT162b2 versus ChAdOx1 as primary doses; 2756(187–1246) and 1250(439–2635) BAU/ml respectively, p=0.003.Anti-S antibodies waned over time. Hierarchical levels of anti-S post-V2 predicted risk of infection; patients with no/low anti-S being at highest risk. VE for preventing infection, hospitalisation and death was 53% (95% CI 6–75), 77% (95% CI 30–92) and 93% (95% CI 59–99) respectively, with no difference seen by vaccine type.Interpretation:Serum anti-S concentrations predict risk of breakthrough infection. Anti-S responses vary dependent upon clinical features, infection history and vaccine type. Monitoring of serological responses may enable individualised approaches

Journal article

Evans RA, Leavy OC, Richardson M, Elneima O, McCauley HJC, Shikotra A, Singapuri A, Sereno M, Saunders RM, Harris VC, Houchen-Wolloff L, Aul R, Beirne P, Bolton CE, Brown JS, Choudhury G, Diar-Bakerly N, Easom N, Echevarria C, Fuld J, Hart N, Hurst J, Jones MG, Parekh D, Pfeffer P, Rahman NM, Rowland-Jones SL, Shah AM, Wootton DG, Chalder T, Davies MJ, De Soyza A, Geddes JR, Greenhalf W, Greening NJ, Heaney LG, Heller S, Howard LS, Jacob J, Jenkins RG, Lord JM, Man WD-C, McCann GP, Neubauer S, Openshaw PJM, Porter JC, Rowland MJ, Scott JT, Semple MG, Singh SJ, Thomas DC, Toshner M, Lewis KE, Thwaites RS, Briggs A, Docherty AB, Kerr S, Lone NI, Quint J, Sheikh A, Thorpe M, Zheng B, Chalmers JD, Ho LP, Horsley A, Marks M, Poinasamy K, Raman B, Harrison EM, Wain LV, Brightling CE, Abel K, Adamali H, Adeloye D, Adeyemi O, Adrego R, Aguilar Jimenez LA, Ahmad S, Ahmad Haider N, Ahmed R, Ahwireng N, Ainsworth M, Al-Sheklly B, Alamoudi A, Ali M, Aljaroof M, All AM, Allan L, Allen RJ, Allerton L, Allsop L, Almeida P, Altmann D, Alvarez Corral M, Amoils S, Anderson D, Antoniades C, Arbane G, Arias A, Armour C, Armstrong L, Armstrong N, Arnold D, Arnold H, Ashish A, Ashworth A, Ashworth M, Aslani S, Assefa-Kebede H, Atkin C, Atkin P, Aung H, Austin L, Avram C, Ayoub A, Babores M, Baggott R, Bagshaw J, Baguley D, Bailey L, Baillie JK, Bain S, Bakali M, Bakau M, Baldry E, Baldwin D, Ballard C, Banerjee A, Bang B, Barker RE, Barman L, Barratt S, Barrett F, Basire D, Basu N, Bates M, Bates A, Batterham R, Baxendale H, Bayes H, Beadsworth M, Beckett P, Beggs M, Begum M, Bell D, Bell R, Bennett K, Beranova E, Bermperi A, Berridge A, Berry C, Betts S, Bevan E, Bhui K, Bingham M, Birchall K, Bishop L, Bisnauthsing K, Blaikely J, Bloss A, Bolger A, Bonnington J, Botkai A, Bourne C, Bourne M, Bramham K, Brear L, Breen G, Breeze J, Bright E, Brill S, Brindle K, Broad L, Broadley A, Brookes C, Broome M, Brown A, Brown A, Brown J, Brown J, Brown M, Brown M, Brown V, Brugha T, Brunskill Net al., 2022, Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study, The Lancet Respiratory Medicine, Vol: 10, Pages: 761-775, ISSN: 2213-2600

BackgroundNo effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge.MethodsThe Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing.Findings2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obes

Journal article

Jesudason S, Hewawasam E, Moloney B, Tan R, Li J, Blakey H, Bramham K, Hall M, Juneja R, Jarvis E, Lightstone L, Lipkin G, Hladunewich MAet al., 2022, Comparison of catheters or new arteriovenous fistulas for commencement of haemodialysis in pregnant women with chronic kidney disease: an international observational study, JOURNAL OF NEPHROLOGY, Vol: 35, Pages: 1689-1698, ISSN: 1121-8428

Journal article

Spensley K, Gleeson S, Martin P, Thomson T, Clarke C, Pickard G, Thomas D, McAdoo S, Randell P, Kelleher P, Bedi R, Lightstone E, Prendecki M, Willicombe Met al., 2022, Comparison of vaccine effectiveness against the Omicron (B.1.1.529) variant in haemodialysis patients, Kidney International Reports, Vol: 7, Pages: 1406-1409, ISSN: 2468-0249

Journal article

Gleeson S, Lightstone L, 2022, BLISS-LN trial revisited: function matters (vol 101, pg 224, 2022), KIDNEY INTERNATIONAL, Vol: 101, Pages: 1302-1302, ISSN: 0085-2538

Journal article

Turner-Stokes T, Edwards H, Lightstone L, 2022, COVID-19 in patients with glomerular disease., Current Opinion in Nephrology and Hypertension, Vol: 31, Pages: 191-198, ISSN: 1062-4821

PURPOSE OF REVIEW: Managing patients with glomerular disease during the COVID-19 pandemic has been challenging, as the infection risk associated with immunosuppression must be balanced against the need to control severe glomerular disease that can lead to kidney failure. This review provides an overview of COVID-19 and the effectiveness of SARS-CoV-2 vaccination in patients with glomerular disease. RECENT FINDINGS: Registry data, although biased towards outcomes of hospitalized patients, suggest that the mortality from COVID-19 is higher in patients with glomerular disease than in the general population. Glucocorticoid use prior to SARS-CoV-2 infection is associated with adverse outcomes from COVID-19. Rituximab significantly attenuates serological responses to both natural infection and vaccination against SARS-CoV-2, although it is not clear whether this leads to adverse outcomes. Case reports of disease flares occurring after vaccination have been reported, but causality in any of these cases has yet to be proven and the absolute risk remains very small. SUMMARY: Patients with glomerular disease represent an at-risk group for severe COVID-19 disease and vaccination is key to reducing this risk. As immunosuppressed patients demonstrate an attenuated response to vaccination, the efficacy of a third primary dose followed by a subsequent booster is being investigated.

Journal article

Beckwith H, Lightstone L, McAdoo S, 2022, Sex and gender in glomerular disease., Seminars in Nephrology, Vol: 42, Pages: 185-196, ISSN: 0270-9295

There is increasing understanding that a multifaceted interplay of sex-dependent genetic and immune dysregulation underpins the development of glomerular disorders. Regional and ethnic variations in glomerular disease incidence make delineating the effects of sex and gender on disease pathophysiology more complex, but there is a marked paucity of research in this area. This review article presents a summary of the current understanding of sex and gender in glomerular disease, highlighting the broader effects of sex and gender on autoimmunity, clinical presentations, and pathophysiology of individual glomerular diseases, as well as exploring sex, gender, and glomerular disease within a wider socioenvironmental context. It is important to specifically consider the effects of sex and gender when presenting and analyzing clinical and scientific studies on glomerular disease. Failure to do so risks promoting disparities within health care provision, neglecting opportunities to identify sex-specific biomarkers, and potentially hindering the development of sex-specific therapies.

Journal article

Waldman M, Soler MJ, Garcia-Carro C, Lightstone L, Turner-Stokes T, Griffith M, Torras J, Martinez Valenzuela L, Bestard O, Geddes C, Flossmann O, Budge KL, Cantarelli C, Fiaccadori E, Delsante M, Morales E, Gutierrez E, Nino-Cruz JA, Martinez-Rueda AJ, Comai G, Bini C, La Manna G, Slon MF, Manrique J, Avello A, Fernandez-Prado R, Ortiz A, Marinaki S, Martin Varas CR, Rabasco Ruiz C, Sierra-Carpio M, Garcia-Agudo R, Juarez GF, Hamilton AJ, Bruchfeld A, Chrysochou C, Howard L, Sinha S, Leach T, Pamplona IA, Maggiore U, Cravedi Pet al., 2022, COVID-19 in Patients with Glomerular Disease: Follow-Up Results from the IRoc-GN International Registry, KIDNEY360, Vol: 3, Pages: 293-306, ISSN: 2641-7650

Journal article

Fakhouri F, Schwotzer N, Cabiddu G, Barratt J, Legardeur H, Garovic V, Orozco-Guillen A, Wetzels J, Daugas E, Moroni G, Noris M, Audard V, Praga M, Llurba E, Wuerzner G, Attini R, Desseauve D, Zakharova E, Luders C, Wiles K, Leone F, Jesudason S, Costedoat-Chalumeau N, Kattah A, Soto-Abraham V, Karras A, Prakash J, Lightstone L, Ronco P, Ponticelli C, Appel G, Remuzzi G, Tsatsaris V, Piccoli GBet al., 2022, Glomerular diseases in pregnancy: pragmatic recommendations for clinical management, KIDNEY INTERNATIONAL, Vol: 103, Pages: 264-281, ISSN: 0085-2538

Journal article

Gleeson S, Lightstone L, 2022, BLISS-LN trial revisited: function matters, KIDNEY INTERNATIONAL, Vol: 101, Pages: 224-226, ISSN: 0085-2538

Journal article

Gilmore A, Wilson H, Cairns T, Botto M, Lightstone L, Bruce I, Cook H, Pickering M, on behalf of the MASTERPLANS Consortiumet al., 2022, Immune gene expression and functional networks in distinct lupus nephritis classes, Lupus Science & Medicine, Vol: 9, ISSN: 2053-8790

Objective: To explore the utility of the NanoString platform in elucidating kidney immune transcripts for class III, IV and V lupus nephritis (LN) using a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) kidney biopsy tissue.Methods: Immune gene transcript analysis was performed using the NanoString nCounter platform on RNA from LN (n=55), thin basement membrane disease (TBM, n=14) and membranous nephropathy (MN, n=9) FFPE kidney biopsy tissue. LN samples consisted of single class III (n=11), IV (n=23) and V (n=21) biopsies with no mixed lesions. Differential gene expression was performed with NanoString nSolver, with visualisations of volcano plots and heatmaps generated in R. Significant transcripts were interrogated to identify functional networks using STRING and Gene ontogeny terms. Results: In comparison to TBM, we identified 52 significantly differentially expressed genes common to all three LN classes. Pathway analysis showed enrichment for type I interferon (IFN) signalling, complement and MHC II pathways, with most showing the highest expression in class IV LN. Our class IV LN biopsies also showed significant upregulation of NF-κB signalling and immunological enrichment in comparison to class V LN biopsies. Transcripts from the type I IFN pathway distinguished class V LN from MN. Conclusion: Our whole kidney section transcriptomic analysis provided insights into the molecular profile of class III, IV and V LN. The data highlighted important pathways common to all three classes and pathways enriched in our class IV LN biopsies. The ability to reveal molecular pathways in LN using FFPE whole biopsy sections could have clinical utility in treatment selection for LN.

Journal article

Greenhalgh T, Griffin S, Gurdasani D, Hamdy A, Katzourakis A, McKee M, Michie S, Pagel C, Roberts A, Yates K, Alwan N, Agius R, Ahmed H, Ashworth S, Augst C, Bacon SL, Bergholtz EJ, Blanchflower D, Bosman A, Ben Alaya NBE, Brown K, Butler M, Byrne M, Cacciola R, Cane DJ, Cascini F, Chahed M, Cheng KK, Costello A, Morris AC, Davies R, Davis C, Delaney B, Dewald D, Drew D, Ewing A, Drury J, Fisman D, Friel S, Gasperowicz M, Grimes DR, Haque Z, Haseltine WA, Hegarty O, Hodes S, Hughes E, Hyde Z, Iannattone L, Jadad AR, Jha N, Jimenez JL, Jimenez JL, Johnson J, Karan A, Khunti K, Khuri-Bulos N, Kim WJ, Knight MJ, Lavoie KL, Lawton T, Lazarus JV, Leonardi AJ, Leshem E, Lightstone L, Markov PV, Martin-Moreno JM, Meier P, Mesiano-Crookston J, Mishra AK, Moore M, Moschos SA, Naylor CD, Nichols T, Nicholl D, Norheim OF, Oliver M, Peters C, Pillay D, Pimenta D, Pirzada K, Pope C, Prather KA, Preest G, Quereshi Z, Rabiei K, Ray J, Reddy KS, Ricciardi W, Rice K, Robertson E, Roberts K, Ryan T, Salisbury H, Scally G, Schooley RT, Shah V, Silver J, Silvey N, Sivan M, Souza LE, Staines A, Tomlinson D, Tukuitonga C, Vincent C, Vipond J, West R, Weyand AC, Ziauddeen Het al., 2022, Covid-19: An urgent call for global "vaccines-plus" action, BMJ-BRITISH MEDICAL JOURNAL, Vol: 376, ISSN: 0959-535X

Journal article

Carter SA, Teng C, Gutman T, Logeman C, Cattran D, Lightstone L, Bagga A, Barbour SJ, Barratt J, Boletis J, Caster DJ, Coppo R, Fervenza FC, Floege J, Hladunewich MA, Hogan JJ, Kitching AR, Lafayette RA, Malvar A, Radhakrishnan J, Rovin BH, Scholes-Robertson N, Trimarchi H, Zhang H, Azukaitis K, Cho Y, Viecelli AK, Dunn L, Harris D, Johnson DW, Kerr PG, Laboi P, Ryan J, Shen J, Ruiz L, Wang AY-M, Lee AHK, Shun SFK, Tong MK-H, Teixeira-Pinto A, Wilkie M, Alexander S, Craig JC, Martin A, Tong Aet al., 2022, A Focus Group Study of Self-Management in Patients With Glomerular Disease, KIDNEY INTERNATIONAL REPORTS, Vol: 7, Pages: 56-67, ISSN: 2468-0249

Journal article

Podos S, Nester C, Appel G, Bomback A, Bouman KP, Cook T, Daina E, Dixon B, Langman C, Lightstone L, Thanassi J, Rice K, Huang M, Parikh SV, Pickering M, Sperati J, Trachtman H, Tumlin J, Wetzels J, Remuzzi Get al., 2022, Clinical and biomarker characteristics of patients with C3G enrolled in two phase II studies investigating the factor D inhibitor danicopan, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 148-148, ISSN: 0161-5890

Conference paper

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