Imperial College London

ProfessorJohnPepper

Faculty of MedicineNational Heart & Lung Institute

Professor of Cardiothoracic Surgery
 
 
 
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Contact

 

+44 (0)20 7351 8530j.pepper

 
 
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Location

 

Dept. of SurgeryBritten WingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

492 results found

Stoica S, Beard C, Takkenberg JJM, Mokhles MM, Turner M, Pepper J, Hopewell-Kelly N, Benedetto U, Nashef SAM, El-Hamamsy I, Skillington P, Glauber M, De Paulis R, Tseng E, Meuris B, Sitges M, Delgado V, Krane M, Kostolny M, Pufulete Met al., 2023, Formal consensus study on surgery to replace the aortic valve in adults aged 18-60 years, HEART, Vol: 109, Pages: 857-865, ISSN: 1355-6037

Journal article

Van Hoof L, Lamberigts M, Noe D, El-Hamamsy I, Lansac E, Kluin J, de Kerchove L, Pepper J, Treasure T, Meuris B, Rega F, Verbrugghe Pet al., 2023, Matched comparison between external aortic root support and valve-sparing root replacement, Heart, Vol: 109, Pages: 832-838, ISSN: 1355-6037

Objectives: Differences in indication and technique make a randomised comparison between valve-sparing root replacement (VSRR) and personalised external aortic root support (PEARS) challenging. We performed a propensity score (PS)-matched comparison of PEARS and VSRR for syndromic root aneurysm.Methods: Patients in the PEARS 200 Database and Aortic Valve Insufficiency and ascending aorta Aneurysm InternATiOnal Registry (undergoing VSRR) with connective tissue disease operated electively for root aneurysm <60 mm with aortic regurgitation (AR) <1/4 were included. Using a PS analysis, 80 patients in each cohort were matched. Survival, freedom from reintervention and from AR ≥2/4 were estimated using a Kaplan-Meier analysis.Results: Median follow-up was 25 and 55 months for 159 PEARS and 142 VSRR patients. Seven (4.4%) patients undergoing PEARS required an intervention for coronary injury or impingement, resulting in one death (0.6%). After VSRR, there were no early deaths, 10 (7%) reinterventions for bleeding and 1 coronary intervention. Survival for matched cohorts at 5 years was similar (PEARS 98% vs VSRR 99%, p=0.99). There was no difference in freedom from valve or ascending aortic/arch reintervention between matched groups. Freedom from AR ≥2/4 at 5 years in the matched cohorts was 97% for PEARS vs 92% for VSRR (p=0.55). There were no type A dissections.Conclusions: VSRR and PEARS offer favourable mid-term survival, freedom from reintervention and preservation of valve function. Both treatments deserve their place in the surgical repertoire, depending on a patient’s disease stage. This study is limited by its retrospective nature and different follow-ups in both cohorts.

Journal article

Zhu Y, Xu XY, Rosendahl U, Pepper J, Mirsadraee Set al., 2023, Advanced risk prediction for aortic dissection patients using imaging-based computational flow analysis, Clinical Radiology, Vol: 78, Pages: e155-e165, ISSN: 0009-9260

Patients with either a repaired or medically managed aortic dissection have varying degrees of risk of developing late complications. High-risk patients would benefit from earlier intervention to improve their long-term survival. Currently serial imaging is used for risk stratification, which is not always reliable. On the other hand, understanding aortic haemodynamics within a dissection is essential to fully evaluate the disease and predict how it may progress. In recent decades, computational fluid dynamics (CFD) has been extensively applied to simulate complex haemodynamics within aortic diseases, and more recently, four-dimensional (4D)-flow magnetic resonance imaging (MRI) techniques have been developed for in vivo haemodynamic measurement. This paper presents a comprehensive review on the application of image-based CFD simulations and 4D-flow MRI analysis for risk prediction in aortic dissection. The key steps involved in patient-specific CFD analyses are demonstrated. Finally, we propose a workflow incorporating computational modelling for personalised assessment to aid in risk stratification and treatment decision-making.

Journal article

Salmasi MY, Alwis S, Cyclewala S, Jarral OA, Mohamed H, Mozalbat D, Nienaber CA, Athanasiou T, Morris-Rosendahl D, Members of the London Aortic Mechanobiology Working Groupet al., 2023, The genetic basis of thoracic aortic disease: The future of aneurysm classification?, Hellenic Journal of Cardiology, Vol: 69, Pages: 41-50, ISSN: 1109-9666

The expansion in the repertoire of genes linked to thoracic aortic aneurysms (TAA) has revolutionised our understanding of the disease process. The clinical benefits of such progress are numerous, particularly helping our understanding of non-syndromic hereditary causes of TAA (HTAAD) and further refinement in the subclassification of disease. Furthermore, the understanding of aortic biomechanics and mechanical homeostasis has been significantly informed by the discovery of deleterious mutations and their effect on aortic phenotype. The drawbacks in genetic testing in TAA lie with the inability to translate genotype to accurate prognostication in the risk of thoracic aortic dissection (TAD), which is a life-threatening condition. Under current guidelines, there are no metrics by which those at risk for dissection with normal aortic diameters may undergo preventive surgery. Future research lies with more advanced genetic diagnosis of HTAAD and investigation of the diverse pathways involved in its pathophysiology, which will i) serve to improve our understanding of the underlying mechanisms, ii) improve guidelines for treatment and iii) prevent complications for HTAAD and sporadic aortopathies.

Journal article

Salmasi MY, Morris-Rosendahl D, Jarral OA, Rosendahl U, Asimakopoulos G, Raja S, Aragon-Martin JA, Child A, Pepper J, Oo A, Athanasiou Tet al., 2022, Determining the genetic contribution in patients with non-syndromic ascending thoracic aortic aneurysms: Correlation with findings from computational pathology, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 366, Pages: 1-9, ISSN: 0167-5273

Journal article

Treasure T, Austin C, Kenny LA, Pepper Jet al., 2022, Personalized external aortic root support in aneurysm disease, Current Opinion in Cardiology, Vol: 37, Pages: 454-458, ISSN: 0268-4705

Purpose of review To bring together and annotate publications about personalised external aortic root support reported in the 18 months preceding submission.Recent findings The total number of personalised external aortic root support (PEARS) operations is now approaching 700 in 30 centres in Australia, Belgium, Brazil, Czech Republic, Great Britain, Greece, Ireland, Malaysia, Netherlands, New Zealand, Poland and Slovakia. There are continued reports of stability of aortic dimensions and aortic valve function with the only exceptions known being where the surgeon has deviated from the instructions for use of the device. The median root diameter of Marfan patients having PEARS was 47 mm suggesting that the existing criterion of 50 mm is due for reconsideration. The peri-operative mortality currently estimated to be less than 0.3%. The first recipient remains alive and well after 18 years. The use of PEARS as an adjunct to the Ross operation to support the pulmonary autograft is being explored in several centres.Summary The operation requires proctoring and adherence to a strict operative protocol and with those precautions excellent results are attained. The evidence and opinions provided in the cited publications indicate that PEARS is a proven and successful prophylactic operation for aortic root aneurysm.

Journal article

Van Hoof L, Rega F, Treasure T, Pepper Jet al., 2022, WHAT'S IN AWRAP?, JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, Vol: 164, Pages: E77-E78, ISSN: 0022-5223

Journal article

Salmasi MYB, Morris-Rosendahl D, Jarral O, Rosendahl U, Asimakopoulos G, Aragon-Martin J, Child A, Pepper J, Oo A, Athanasiou Tet al., 2022, Determining the genetic contribution in patients with non-syndromic ascending thoracic aortic aneurysms: Correlation with findings from computational pathology, International Journal of Cardiology, ISSN: 0167-5273

Journal article

Zhu Y, Mirsadraee S, Rosendahl U, Pepper J, Xu Xet al., 2022, Fluid-structure interaction simulations of repaired type A aortic dissection: a comprehensive comparison with rigid wall models, Frontiers in Physiology, Vol: 13, ISSN: 1664-042X

This study aimed to evaluate the effect of aortic wall compliance on intraluminal hemodynamics within surgically repaired type A aortic dissection (TAAD). Fully coupled two-way fluid-structure interaction (FSI) simulations were performed on two patient-specific post-surgery TAAD models reconstructed from computed tomography angiography images. Our FSI model incorporated prestress and different material properties for the aorta and graft. Computational results, including velocity, wall shear stress (WSS) and pressure difference between the true and false lumen, were compared between the FSI and rigid wall simulations. It was found that the FSI model predicted lower blood velocities and WSS along the dissected aorta. In particular, the area exposed to low time-averaged WSS (≤0.2 Pa) was increased from 21 cm2 (rigid) to 38 cm2 (FSI) in patient 1 and from 35 cm2 (rigid) to 144 cm2 (FSI) in patient 2. FSI models also produced more disturbed flow where much larger regions presented with higher turbulence intensity as compared to the rigid wall models. The effect of wall compliance on pressure difference between the true and false lumen was insignificant, with the maximum difference between FSI and rigid models being less than 0.25 mmHg for the two patient-specific models. Comparisons of simulation results for models with different Young’s moduli revealed that a more compliant wall resulted in further reduction in velocity and WSS magnitudes because of increased displacements. This study demonstrated the importance of FSI simulation for accurate prediction of low WSS regions in surgically repaired TAAD, but a rigid wall computational fluid dynamics simulation would be sufficient for prediction of luminal pressure difference.

Journal article

Zientara A, Pepper J, Quarto C, 2022, Who took away my aortic valve? COMMENT, EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, Vol: 61, Pages: 187-188, ISSN: 1010-7940

Journal article

Youssefi P, Pepper J, 2021, A new age of aortic valve repair, EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, Vol: 60, Pages: 1062-1063, ISSN: 1010-7940

Journal article

Van Hoof L, Rega F, Golesworthy T, Verbrugghe P, Austin C, Takkenberg JJM, Pepper JR, Treasure Tet al., 2021, Personalised external aortic root support for elective treatment of aortic root dilation in 200 patients, HEART, Vol: 107, Pages: 1790-1795, ISSN: 1355-6037

Journal article

Vassiliou V, Pavlou M, Malley T, Halliday B, Tsampasian V, Raphael C, Tse G, Vieira M, Auger D, Everett R, Chin C, Alpendurada F, Pepper J, Pennell D, Newby D, Jabbour A, Dweck M, Prasad Set al., 2021, A novel cardiovascular magnetic resonance risk score for predicting mortality following surgical aortic valve replacement, Scientific Reports, Vol: 11, ISSN: 2045-2322

The increasing prevalence of patients with aortic stenosis worldwide highlights a clinical need for improved and accurate prediction of clinical outcomes following surgery. We investigated patient demographic and cardiovascular magnetic resonance (CMR) characteristics to formulate a dedicated risk score estimating long-term survival following surgery. We recruited consecutive patients undergoing CMR with gadolinium administration prior to surgical aortic valve replacement from 2003 to 2016 in two UK centres. The outcome was overall mortality. A total of 250 patients were included (68 ± 12 years, male 185 (60%), with pre-operative mean aortic valve area 0.93 ± 0.32cm2, LVEF 62 ± 17%) and followed for 6.0 ± 3.3 years. Sixty-one deaths occurred, with 10-year mortality of 23.6%. Multivariable analysis showed that increasing age (HR 1.04, P = 0.005), use of antiplatelet therapy (HR 0.54, P = 0.027), presence of infarction or midwall late gadolinium enhancement (HR 1.52 and HR 2.14 respectively, combined P = 0.12), higher indexed left ventricular stroke volume (HR 0.98, P = 0.043) and higher left atrial ejection fraction (HR 0.98, P = 0.083) associated with mortality and developed a risk score with good discrimination. This is the first dedicated risk prediction score for patients with aortic stenosis undergoing surgical aortic valve replacement providing an individualised estimate for overall mortality. This model can help clinicians individualising medical and surgical care.

Journal article

Vlastos D, Chauhan I, Mensah K, Cannoletta M, Asonitis A, Elfadil A, Petrou M, De Souza A, Quarto C, Bhudia SK, Rosendahl U, Pepper J, Asimakopoulos Get al., 2021, The impact of COVID-19 pandemic on aortic valve surgical service: a single centre experience, BMC CARDIOVASCULAR DISORDERS, Vol: 21, ISSN: 1471-2261

Journal article

Bleakley C, de Marvao A, Athayde A, Kuhn T, Xu T, Weaver C, Singh S, Hill J, Pepper J, Price Set al., 2021, The Impact of Norepinephrine on Myocardial Perfusion in Critical Illness, JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY, Vol: 34, Pages: 1019-1020, ISSN: 0894-7317

Journal article

Khir AW, Pepper JR, 2021, Mechanical support of the heart: Where are we heading?, INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS, Vol: 44, Pages: 590-591, ISSN: 0391-3988

Journal article

Zhu Y, Mirsadraee S, Asimakopoulos G, Gambaro A, Rosendahl U, Pepper J, Xu Xet al., 2021, Association of hemodynamic factors and progressive aortic dilatation following type A aortic dissection surgical repair, Scientific Reports, Vol: 11, ISSN: 2045-2322

Type A aortic dissection (TAAD) involves the ascending aorta or the arch. Acute TAAD usually requires urgent replacement of the ascending aorta. However, a subset of these patients develops aortic rupture due to further dilatation of the residual dissected aorta. There is currently no reliable means to predict the risk of dilatation following TAAD repair. In this study, we performed a comprehensive morphological and hemodynamic analysis for patients with and without progressive aortic dilatation following surgical replacement of the ascending aorta. Patient-specific models of repaired TAAD were reconstructed from post-surgery computed tomography images for detailed computational fluid dynamic analysis. Geometric and hemodynamic parameters were evaluated and compared between patients with stable aortic diameters (N = 9) and those with aortic dilatation (N = 8). Our results showed that the number of re-entry tears and true/false lumen pressure difference were significantly different between the two groups. Patients with progressive aortic dilatation had higher luminal pressure difference (6.7 [4.6, 10.9] vs. 0.9 [0.5, 2.3] mmHg; P = 0.001) and fewer re-entry tears (1.5 [1, 2.8] vs. 5 [3.3, 7.5]; P = 0.02) compared to patients with stable aortic diameters, suggesting that these factors may serve as potential predictors of aneurysmal dilatation following surgical repair of TAAD.

Journal article

Jin XY, Petrou M, Hu JT, Nicol ED, Pepper JRet al., 2021, Challenges and opportunities in improving left ventricular remodelling and clinical outcome following surgical and trans-catheter aortic valve replacement, Frontiers of Medicine, Vol: 15, Pages: 416-437, ISSN: 1673-7342

Over the last half century, surgical aortic valve replacement (SAVR) has evolved to offer a durable and efficient valve haemodynamically, with low procedural complications that allows favourable remodelling of left ventricular (LV) structure and function. The latter has become more challenging among elderly patients, particularly following trans-catheter aortic valve implantation (TAVI). Precise understanding of myocardial adaptation to pressure and volume overloading and its responses to valve surgery requires comprehensive assessments from aortic valve energy loss, valvular-vascular impedance to myocardial activation, force-velocity relationship, and myocardial strain. LV hypertrophy and myocardial fibrosis remains as the structural and morphological focus in this endeavour. Early intervention in asymptomatic aortic stenosis or regurgitation along with individualised management of hypertension and atrial fibrillation is likely to improve patient outcome. Physiological pacing via the His-Purkinje system for conduction abnormalities, further reduction in para-valvular aortic regurgitation along with therapy of angiotensin receptor blockade will improve patient outcome by facilitating hypertrophy regression, LV coordinate contraction, and global vascular function. TAVI leaflet thromboses require anticoagulation while impaired access to coronary ostia risks future TAVI-in-TAVI or coronary interventions. Until comparable long-term durability and the resolution of TAVI related complications become available, SAVR remains the first choice for lower risk younger patients.

Journal article

Melina G, De Robertis F, Gaer JA, Angeloni E, El-Hamamsy I, Bahrami T, Pepper JR, Takkenberg JJM, Yacoub MHet al., 2021, Long-term survival after xenograft versus homograft aortic root replacement: Results from a prospective randomized trial, JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, Vol: 161, Pages: 57-65, ISSN: 0022-5223

Journal article

Salmasi M, Jarral OA, Pirola S, Sasidharan S, Pepper J, Oo A, Moore J, Xu XY, Athanasiou Tet al., 2020, In-vivo blood flow parameters can predict at-risk aortic aneurysms and dissection: a comprehensive biomechanics model, EUROPEAN HEART JOURNAL, Vol: 41, Pages: 2339-2339, ISSN: 0195-668X

Journal article

Horke A, Tudorache I, Laufer G, Andreas M, Pomar JL, Pereda D, Quintana E, Sitges M, Meyns B, Rega F, Hazekamp M, Hubler M, Schmiady M, Pepper J, Rosendahl U, Lichtenberg A, Akhyari P, Jashari R, Boethig D, Bobylev D, Avsar M, Cebotari S, Haverich A, Sarikouch Set al., 2020, Early results from a prospective, single-arm European trial on decellularized allografts for aortic valve replacement: the ARISE study and ARISE Registry data, EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, Vol: 58, Pages: 1045-1053, ISSN: 1010-7940

Journal article

Jin XY, Sayeed R, Pepper J, Petrou Met al., 2020, Mitigating cardiac dysfunction by TOE-guided cardioplegia and mitral valve repair, ASIAN CARDIOVASCULAR & THORACIC ANNALS, Vol: 28, Pages: 427-430, ISSN: 0218-4923

Journal article

Nemec P, Pepper J, Fila P, 2020, Personalized external aortic root support, INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY, Vol: 31, Pages: 342-345, ISSN: 1569-9293

Journal article

Lyon A, Babalis D, Morley-Smith AC, Hedger M, Suarez Barrientos A, Foldes G, Couch LS, Chowdhury RA, Tzortzis KN, Peters NS, Rog-Zielinska EA, Yang YH, Welch S, Bowles CT, Rahman Haley S, Bell AR, Rice A, Sasikaran T, Johnson NA, Falaschetti E, Parameshwar J, Lewis C, Tsui S, Simon A, Pepper J, Rudy JJ, Zsebo KM, MacLeod KT, Terracciano CM, Hajjar RJ, Banner N, Harding SEet al., 2020, Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device – the SERCA-LVAD TRIAL, Gene Therapy, Vol: 27, Pages: 579-590, ISSN: 0969-7128

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. Enrolled subjects were randomised to receive a single intracoronary infusion of 1x1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort, which may help guide future trial design.

Journal article

Salmasi MY, Al-Saadi N, Hartley P, Jarral OA, Raja S, Hussein M, Redhead J, Rosendahl U, Nienaber CA, Pepper JR, Oo AY, Athanasiou Tet al., 2020, The risk of misdiagnosis in acute thoracic aortic dissection: a review of current guidelines, HEART, Vol: 106, Pages: 885-891, ISSN: 1355-6037

Journal article

Jarral OA, Tan MKH, Salmasi MY, Pirola S, Pepper JR, O'Regan DP, Xu XY, Athanasiou Tet al., 2020, Phase-contrast magnetic resonance imaging and computational fluid dynamics assessment of thoracic aorta blood flow: a literature review, European Journal of Cardio-Thoracic Surgery, Vol: 57, Pages: 438-446, ISSN: 1010-7940

The death rate from thoracic aortic disease is on the rise and represents a growing global health concern as patients are often asymptomatic before acute events, which have devastating effects on health-related quality of life. Biomechanical factors have been found to play a major role in the development of both acquired and congenital aortic diseases. However, much is still unknown and translational benefits of this knowledge are yet to be seen. Phase-contrast cardiovascular magnetic resonance imaging of thoracic aortic blood flow has emerged as an exceptionally powerful non-invasive tool enabling visualization of complex flow patterns, and calculation of variables such as wall shear stress. This has led to multiple new findings in the areas of phenotype-dependent bicuspid valve flow patterns, thoracic aortic aneurysm formation and aortic prosthesis performance assessment. Phase-contrast cardiovascular magnetic resonance imaging has also been used in conjunction with computational fluid modelling techniques to produce even more sophisticated analyses, by allowing the calculation of haemodynamic variables with exceptional temporal and spatial resolution. Translationally, these technologies may potentially play a major role in the emergence of precision medicine and patient-specific treatments in patients with aortic disease. This clinically focused review will provide a systematic overview of key insights from published studies to date.

Journal article

Caliskan E, De Souza DR, Boening A, Liakopoulos OJ, Choi Y-H, Pepper J, Gibson CM, Perrault LP, Wolf RK, Kim K-B, Emmert MYet al., 2020, Saphenous vein grafts in contemporary coronary artery bypass graft surgery, NATURE REVIEWS CARDIOLOGY, Vol: 17, Pages: 155-169, ISSN: 1759-5002

Journal article

Salmasi MY, Hartley P, Hussein M, Jarral O, Pepper J, Nienaber C, Athanasiou Tet al., 2020, Diagnosis and management of acute Type-A aortic dissection in emergency departments: Results of a UK national survey, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 300, Pages: 50-59, ISSN: 0167-5273

Journal article

Pepper J, Izgi C, Golesworthy TJ, Takkenberg JJM, Treasure Tet al., 2020, Personalised external aortic root support (PEARS) to stabilise an aortic root aneurysm., Br J Cardiol, Vol: 27

Patients with congenitally determined aortic root aneurysms are at risk of aortic valve regurgitation, aortic dissection, rupture and death. Personalised external aortic root support (PEARS) may provide an alternative to aortic root replacement. This was a multi-centre, prospective cohort of all consecutive patients who received ExoVasc mesh implants for a dilated aortic root between 2004 and 2017. Baseline and peri-operative characteristics, as well as early postoperative outcomes are described, and time-related survival and re-operation free survival are estimated using the Kaplan-Meier method. From 2004 through 2017, 117 consecutive patients have received ExoVasc mesh implants for aortic root aneurysm. The inclusion criteria were an aortic root/sinus of Valsalva and ascending aorta with asymptomatic dilatation of between 40 and 50 mm in diameter in patients aged 16 years or more. Patients with more than mild aortic regurgitation were excluded. There was one early death. The length of stay was within seven days in 75% of patients. In conclusion, the operation achieves the objectives of valve-sparing root replacement. PEARS may be seen as a low-risk conservative operation, which can be applied earlier on in the disease process, and which is complementary to more invasive procedures, such as valve-sparing root replacement or total root replacement.

Journal article

Pepper J, 2019, Faulty devices: how does cardiology compare to aviation?, EUROPEAN HEART JOURNAL, Vol: 40, Pages: 2103-2106, ISSN: 0195-668X

Journal article

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