Imperial College London

Professor Nicholas Simmonds

Faculty of MedicineNational Heart & Lung Institute

Professor of Practice (Respiratory Medicine)
 
 
 
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Contact

 

+44 (0)20 7351 8997n.simmonds

 
 
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Location

 

Dept of Cystic FibrosisRoyal BromptonRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

161 results found

Sloan CM, Sherrard LJ, Einarsson GG, Dupont LJ, Koningsbruggen-Rietschel SV, Simmonds NJ, Downey DGet al., 2024, Inhaled antimicrobial prescribing for Pseudomonas aeruginosa infections in Europe., J Cyst Fibros

BACKGROUND: Prescribers have an increasing range of inhaled antimicrobial formulations to choose from when prescribing both eradication and chronic suppression regimens in cystic fibrosis (CF). This study aimed to investigate the decision-making process behind prescribing of inhaled antimicrobials for Pseudomonas aeruginosa infections. METHODS: A questionnaire was developed using Microsoft Forms and then forwarded to 57 Principal Investigators (PIs), at each of the CF centres within the European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN). Data collection occurred between November 2021 and February 2022. RESULTS: The response rate was 90 % (n = 51/57 PIs), with at least 50 % of CF centers in each of the 17 countries represented in the ECFS-CTN. Physicians used a median of eight factors in their decision-making process with delivery formulations (92.2 %), adherence history (84.3 %), and antibiotic side-effect profile (76.5 %) often selected. Nebulised tobramycin or colistin were frequently selected as the inhaled antimicrobial in first-line eradication (n = 45, 88.2 %) and chronic suppression regimens (n = 42, 82.4 %). Combination regimens were more often chosen in eradication (first-line: n = 35, 68.6 %, second-line: n = 34, 66.7 %) and later chronic suppression regimens (third-line: n = 27, 52.9 %) than monotherapy. For pwCF also prescribed CFTR modulator therapies, most PIs did not alter inhaled antimicrobial regimens (n = 40, 78.4 %), with few pwCF (n = 18, 35.3 %) or PIs (n = 10, 19.6 %) deciding to stop inhaled antimicrobials. CONCLUSIONS: The inhaled antimicrobial prescribing decision-making process is multifactorial. Nebulised tobramycin or colistin are often used in initial eradication and chronic suppression regimens. To date, CFTR modulator therapy has had a limited impact on the prescribing of inhaled antimicrobial regimens.

Journal article

Hanger S, Felton I, Ukor E-F, Bowman E, Caldwell C, Banya W, Madge S, Jones AL, Simmonds NJet al., 2024, The effectiveness of CFTR modulators in people with CF and rare mutations: A real-world study., Pediatr Pulmonol, Vol: 59, Pages: 221-224

Journal article

Castellani C, Raraigh K, Nährlich L, Sermet-Gaudelus I, Simmonds NJet al., 2023, Reply to the letter Regarding the article entitled "Standards for the care of people with CF: a timely and accurate diagnosis"., J Cyst Fibros

Journal article

Davies J, Matthews J, Dobra R, Wilson G, Allen L, Bossley C, Brendell R, Brugha R, Brown D, Brown S, Cadiente S, Cameron L, Davies G, Dawson C, Elborn S, Hughes D, Longmate J, Macedo P, Pappas L, Pao C, Round C, Ruiz G, Saunders C, Shafi N, Simmonds N, Waller M, Watson Det al., 2023, Levelling the playing field through the London Network of the UK Clinical Trials Accelerator Platform, Contemporary Clinical Trials Communications, ISSN: 2451-8654

Journal article

Dobra R, Pinnell S, Jones A, Madge S, Simmonds NJ, Davies JCet al., 2023, How representative are clinical trial cohorts of the general CF population? Implications for trial planning., J Cyst Fibros

Understanding the number of patients eligible to participate in research is important to design protocols and define research priorities. We reviewed the records of all patients with CF, age 12+, who receive care at our centre. We assessed their eligibility for trial participation based on common trial inclusion/exclusion criteria. 643 patients were included in the analysis, 31 were modulator ineligible(MI). Only 198(31 %) of the total cohort and 7(23 %) of the MI cohort were eligible for participation based on the hypothetical criteria. The most common reason for ineligibility was ppFEV1 ≥90 % followed by clinical instability, complex comorbidity and anticipated inability to adhere to the protocol. We suggest this would be a useful exercise for centres planning to either participate in, or refer subjects into, upcoming trials to undertake for their own cohort. We also make suggestions for protocol designs that optimise the number of patients who are eligible to participate.

Journal article

Castellani C, Simmonds NJ, Barben J, Addy C, Bevan A, Burgel P-R, Drevinek P, Gartner S, Gramegna A, Lammertyn E, Landau EEC, Middleton PG, Plant BJ, Smyth AR, van Koningsbruggen-Rietschel S, Girodon E, Kashirskaya N, Munck A, Nährlich L, Raraigh K, Sermet-Gaudelus I, Sommerburg O, Southern KWet al., 2023, Standards for the care of people with cystic fibrosis (CF): A timely and accurate diagnosis., J Cyst Fibros, Vol: 22, Pages: 963-968

There is considerable activity with respect to diagnosis in the field of cystic fibrosis (CF). This relates primarily to developments in newborn bloodspot screening (NBS), more extensive gene analysis and improved characterisation of CFTR-related disorder (CFTR-RD). This is particularly pertinent with respect to accessibility to variant-specific therapy (VST), a transformational intervention for people with CF with eligible CFTR gene variants. This advance reinforces the need for a timely and accurate diagnosis. In the future, there is potential for trials to assess effectiveness of variant-specific therapy for CFTR-RD. The guidance in this paper reaffirms previous standards, clarifies a number of issues, and integrates emerging evidence. Timely and accurate diagnosis has never been more important for people with CF.

Journal article

De Wachter E, Davies JC, Simmonds NJ, Castellani C, de Winter-de Groot KM, Munck A, Proesmans M, Southern KW, Barben Jet al., 2023, Letter to the editor: Risk of false newborn screening after intra-uterine exposure to ETI., J Cyst Fibros

Journal article

Middleton PG, Simmonds NJ, 2023, Cystic fibrosis modulator therapy can reverse cystic bronchiectasis, RESPIROLOGY CASE REPORTS, Vol: 11, ISSN: 2051-3380

Journal article

Barry PJJ, Simmonds NJJ, 2023, Diagnosing Cystic Fibrosis in Adults, SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 44, Pages: 242-251, ISSN: 1069-3424

Journal article

Cameron RA, Rowley M, Simmonds NJ, Whitty JA, Carr SBet al., 2023, The Response, CHEST, Vol: 163, Pages: E194-E195, ISSN: 0012-3692

Journal article

Davies J, Hughes D, Rosenthal M, Cuthbertson L, ramadan N, Felton I, Simmonds N, Loebinger M, price H, Armstrong-James D, elborn S, Cookson W, Moffatt Met al., 2023, An invisible threat? Aspergillus positive cultures and co-infecting bacteria in airway sample, Journal of Cystic Fibrosis, Vol: 22, Pages: 320-326, ISSN: 1569-1993

BackgroundAspergillus fumigatus (Af) infection is associated with poor lung health in chronic suppurative lung diseases but often goes undetected. We hypothesised that inhibition of Af growth by Pseudomonas aeruginosa (Pa) increases the frequency of false-negative Af culture in co-infected people. Using a substantial group of cystic fibrosis (CF) airway samples, we assessed the relationship between Af and bacterial pathogens, additionally comparing fungal culture with next-generation sequencing.MethodsFrequency of co-culture was assessed for 44,554 sputum/BAL cultures, from 1,367 CF patients between the years 2010–2020. In a subgroup, Internal Transcribed Spacer-2 (ITS2) fungal sequencing was used to determine sequencing-positive, culture-negative (S+/C-) rates.ResultsPa+ samples were nearly 40% less likely (P<0.0001) than Pa- samples to culture Af, an effect that was also seen with some other Gram-negative isolates. This impact varied with Pa density and appeared to be moderated by Staphylococcus aureus co-infection. Sequencing identified Af-S+/C- for 40.1% of tested sputa. Samples with Pa had higher rates of Af-S+/C- (49.3%) than those without (35.7%; RR 1.38 [1.02–1.93], P<0.05). Af-S+/C- rate was not changed by other common bacterial infections. Pa did not affect the S+/C- rates of Candida, Exophiala or Scedosporium.ConclusionsPa/ Af co-positive cultures are less common than expected in CF. Our findings suggest an Af-positive culture is less likely in the presence of Pa. Interpretation of negative cultures should be cautious, particularly in Pa-positive samples, and a companion molecular diagnostic could be useful. Further work investigating mechanisms, alternative detection techniques and other chronic suppurative lung diseases is needed.

Journal article

Simmonds NJ, van der Ent CK, Colombo C, Kinnman N, DeSouza C, Thorat T, Chew ML, Chandarana K, Castellani Cet al., 2023, VOCAL: An observational study of ivacaftor for people with cystic fibrosis and selected non-G551D-CFTR gating mutations *, JOURNAL OF CYSTIC FIBROSIS, Vol: 22, Pages: 124-131, ISSN: 1569-1993

Journal article

Khan MS, Douglas P, Hansell A, Simmonds N, Piel Fet al., 2022, Assessing the health risk of living near composting facilities on lung health, fungal and bacterial disease in cystic fibrosis: a UK CF Registry study, Environmental Health, Vol: 21, Pages: 1-13, ISSN: 1476-069X

AimTo explore the health risk of living near permitted composting sites (PCSs) on disease severity in children and adults with cystic fibrosis (CF) across the UK. MethodsA semi-individual cross-sectional study was used to examine the risk of disease severity in people with CF (pwCF) within and beyond 4 km of PCSs in the UK in 2016. All pwCF registered in the UK CF Registry were eligible for this study. Linear and Poisson regressions, adjusted for age, gender, genotype, BMI, Pseudomonas aeruginosa and deprivation, were used to quantify associations between distance to a PCS and percent predicted forced expiratory volume in one second (ppFEV1), pulmonary exacerbations (#IVdays), and fungal and bacterial infections.ResultsThe mean age of the 9,361 pwCF (3,931 children and 5,430 adults) studied was 20.1 (SD = 14.1) years; 53.3% were male; and 49.2% were homozygous F508del. Over 10% of pwCF (n = 1,015) lived within 4 km of a PCS. We found no statistically significant difference in ppFEV1 and #IVdays/year in children. However, in adults, ppFEV1 was -1.07% lower (95% confidence interval (CI): -2.29%, 0.16%) and #IVdays/year were 1.02 day higher (95%CI: 1.01, 1.04) within 4 km of a PCS. Furthermore, there were statistically significant differences in mean ppFEV1 in CF adults with Aspergillus fumigatus (58.2.% vs 62.0%, p = 0.005) and Candida spp. (56.9% vs 59.9%, p = 0.029) residing within 4 km of a PCS. No associations were identified for allergic bronchopulmonary aspergillosis, P. aeruginosa or Staphylococcus aureus.ConclusionsThis novel national study provides evidence that adults with CF living near a PCS may experience small reductions in lung function, an increased risk of pulmonary exacerbations, and more frequent fungal infections. If confirmed by studies using refined exposure assessment methods accounting for bioaerosol dispersion, these results could have important implications for the living environment of

Journal article

Cameron RA, Office D, Matthews J, Rowley M, Abbott J, Simmonds NJ, Whitty JA, Carr SBet al., 2022, Treatment Preference Among People With Cystic Fibrosis The Importance of Reducing Treatment Burden, CHEST, Vol: 162, Pages: 1241-1254, ISSN: 0012-3692

Journal article

Rehman KU, Tausan M, Ramadan N, Felton I, Ukor E, Madge S, Jones A, Simmonds NJet al., 2022, REMOTE RESPIRATORY SAMPLING AND UNUSUAL PSEUDOMONAS GROWTHS IN ADULTS WITH CYSTIC FIBROSIS: IS THERE A LINK, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A119-A120, ISSN: 0040-6376

Conference paper

Castellani C, De Boeck K, De Wachter E, Sermet-Gaudelus I, Simmonds NJ, Southern KWet al., 2022, ECFS standards of care on CFTR-related disorders: Updated diagnostic criteria, JOURNAL OF CYSTIC FIBROSIS, Vol: 21, Pages: 908-921, ISSN: 1569-1993

Journal article

Tanner KT, Daniel RM, Bilton D, Simmonds NJ, Sharples LD, Keogh RHet al., 2022, Mediation of the total effect of cystic fibrosis-related diabetes on mortality: A UK Cystic Fibrosis Registry cohort study, DIABETIC MEDICINE, Vol: 39, ISSN: 0742-3071

Journal article

Cheong J, Boreland S, Belkarty B, Jones A, Felton I, Ukor E, Stowell J, Jose R, Madge S, Wilkins J, Frost E, Premachandra P, Loebinger M, Drobniewski F, Simmonds N, Shah Aet al., 2022, Implementing tablet-based ototoxicity screening in adult respiratory patients, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Stanford GE, Jones M, Charman SC, Bilton D, Usmani OS, Davies JC, Simmonds NJet al., 2022, Clinimetric analysis of outcome measures for airway clearance in people with cystic fibrosis: a systematic review, Therapeutic Advances in Respiratory Disease, Vol: 16, Pages: 1-12, ISSN: 1753-4666

Background:Airway clearance techniques (ACTs) are integral to cystic fibrosis (CF) management. However, there is no consensus as to which outcome measures (OMs) are best for assessing ACT efficacy.Objectives:To summarise OMs that have been assessed for their clinimetric properties (including validity, feasibility, reliability, and reproducibility) within the context of ACT research in CF.Design and Methods:A systematic review was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) standards. Any parallel or cross-over randomised controlled trial (RCT) investigating outcome measures for ACT in the CF population were eligible for inclusion. The search was performed in five medical databases, clinicaltrials.gov, and abstracts from international CF conferences. The authors planned to independently assess study quality and risk of bias using the COnsensus-based Standards for the selection of health status Measurement InstrumeNts (COSMIN) risk of bias checklist with external validity assessment based upon study details (participants and study intervention). Two review authors (GS and MJ) independently screened search results against inclusion criteria, and further data extraction were planned but not required.Results:No completed RCTs from the 187 studies identified met inclusion criteria for the primary or post hoc secondary objective. Two ongoing trials were identified.Discussion and conclusion:This empty systematic review highlights that high-quality RCTs are urgently needed to investigate and validate the clinimetric properties of OMs used to assess ACT efficacy. With the changing demographics of CF combined with the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, an accurate assessment of the current benefit of ACT or the effect of ACT withdrawal is a high priority for clinical practice and future research; OMs which have been validated for this purpose are essenti

Journal article

Carr SB, McClenaghan E, Elbert A, Faro A, Cosgriff R, Abdrakhmanov O, Brownlee K, Burgel P-R, Byrnes CA, Cheng SY, Colombo C, Corvol H, Daneau G, Goss CH, Gulmans V, Gutierrez H, Harutyunyan S, Helmick M, Jung A, Kashirskaya N, McKone E, Melo J, Middleton PG, Mondejar-Lopez P, de Monestrol I, Naehrlich L, Padoan R, Parker M, Pastor-Vivero MD, Rizvi S, Ruseckaite R, Salvatore M, Da Silva-Filho LVRF, Versmessen N, Zampoli M, Marshall BC, Stephenson ALet al., 2022, Factors associated with clinical progression to severe COVID-19 in people with cystic fibrosis: A global observational study, JOURNAL OF CYSTIC FIBROSIS, Vol: 21, Pages: E221-E231, ISSN: 1569-1993

Journal article

Balfour-Lynn IM, Puckey M, Simmonds NJ, Davies JCet al., 2022, Revisiting a diagnosis of cystic fibrosis - Uncertainties and considerations, PAEDIATRIC RESPIRATORY REVIEWS, Vol: 42, Pages: 29-34, ISSN: 1526-0542

Journal article

Altabee R, Carr SB, Abbott J, Cameron R, Office D, Matthews J, Simmonds N, Cosgriff R, Turner D, Whitty Jet al., 2022, Exploring the nature of perceived treatment burden: a study to compare treatment burden measures in adults with cystic fibrosis [version 1; peer review: 2 approved]., NIHR Open Res, Vol: 2

BACKGROUND: Despite the importance of reducing treatment burden for people with cystic fibrosis (CF), it has not been fully understood as a concept. This study aims to quantify the treatment burden perceived by CF adults and explore the association between different validated treatment burden measures. METHODS: This is a cross-sectional observational study of CF adults attending a single large UK adult center. Participants completed an online survey that contained three different treatment burden scales; CF Questionnaire-Revised (CFQ-R) subscale, CF Quality of Life (CFQoL) subscale, and the generic multimorbidity treatment burden questionnaire (MTBQ). RESULTS: Among 101 participants, the median reported treatment burden by the CFQ-R subscale was 55.5 (IQR 33.3 - 66.6), the CFQoL subscale was 66.6 (IQR 46.6 - 86.6), and the MTBQ reversed global score was 84.6 (IQR 73.1 - 92.3). No correlation was found between respondents' demographic or clinical variables and treatment burden measured via any of the three measures. All treatment burden measures showed correlations against each other. More treatments were associated with high treatment burden as measured by the CFQ-R, CFQoL subscales, and the MTBQ. However, longer treatment time and more complex treatment plans were correlated with high treatment burden as measured by the CFQ-R and CFQoL subscales, but not with the MTBQ. CONCLUSIONS: Treatment burden is a substantial issue in CF. Currently, the only available way to evaluate it is with the CF-specific quality of life measure treatment burden subscales (CFQ-R and CFQoL); both indicated that treatment burden increases with more treatments, longer treatment time, and more complex treatments.

Journal article

Archangelidi O, Cullinan P, Simmonds NJ, Mentzakis E, Peckham D, Bilton D, Carr SBet al., 2022, Incidence and risk factors of cancer in individuals with cystic fibrosis in the UK; a case-control study., Journal of Cystic Fibrosis, Vol: 21, Pages: 302-308, ISSN: 1569-1993

To assess cancer incidence in the UK cystic fibrosis (CF) population and determine the associated risk factors, we undertook a nested case-control study of patients with CF, registered with the UK CF Registry. Each case with a first reported cancer between 1999 and 2017 was matched with up to 4 controls: by age (±2-years) and year of cancer diagnosis. Conditional logistic regressions were adjusted for sex, lung function (FEV1%), CF related diabetes (CFRD), F508del status, transplant status, DIOS, gastro-oesophageal reflux disease, meconium ileus, Pseudomonas aeruginosa infection, pancreatic insufficiency, proton pump inhibitor (PPI) use, IV antibiotic days and BMI. Results: From 12,886 registered patients, 146 (1.1%) cases of malignancy were identified with 14.3% of cases occurring post solid organ transplant. Site of primary cancer was available for 98 patients: 22% were gastro-intestinal in origin (77% lower, 23% upper GI), 13% skin, 13% breast and 11% lymphomas/leukaemia. In univariable analysis, transplantation increased the odds of reporting any cancer by 2.46 times (95%CI: 1.3-4.6). CFRD also increased the odds of reporting any cancer (OR 2.35; CI: 1.37-4.0) and PPI use (OR 2.0; CI 1.28-3.19). In the multivariable models significant associations with CFRD and transplant remained, while PA infection, PPI use and being overweight showed increased, but statistically insignificant risks. The incidence of GI cancer was strongly associated with CFRD (OR=4.04; 1.47-11.1). Conclusions: We observed a high incidence of lower GI cancers in our cohort which was significantly affected by the presence of CFRD. Screening for gastrointestinal cancers could benefit patients at higher risk.

Journal article

Cirilli N, Southern KW, Barben J, Vermeulen F, Munck A, Wilschanski M, Nguyen-Khoa T, Aralica M, Simmonds NJ, De Wachter E, ECFS Diagnost Network Working Grp ECFSDNWet al., 2022, Standards of care guidance for sweat testing; phase two of the ECFS quality improvement programme, JOURNAL OF CYSTIC FIBROSIS, Vol: 21, Pages: 434-441, ISSN: 1569-1993

Journal article

Simmonds NJ, van der Ent K, Colombo C, Kinnman N, DeSouza C, Thorat T, Chandarana K, Castellani Cet al., 2021, OBSERVATIONAL STUDY OF IVACAFTOR IN PEOPLE WITH CYSTIC FIBROSIS AND SELECTED NON-G551D GATING MUTATIONS: FINAL RESULTS FROM VOCAL, Publisher: BMJ PUBLISHING GROUP, Pages: A40-A41, ISSN: 0040-6376

Conference paper

Castellani C, Simmonds NJ, Colombo C, Kinnman N, DeSouza C, Thorat T, Chew M, Chandarana K, van der Ent Ket al., 2021, RESPIRATORY MICROBIOLOGY OUTCOMES FROM AN OBSERVATIONAL STUDY OF IVACAFTOR IN PEOPLE WITH CYSTIC FIBROSIS AND NON-G551D GATING MUTATIONS (VOCAL), Publisher: BMJ PUBLISHING GROUP, Pages: A41-A41, ISSN: 0040-6376

Conference paper

Dobra R, Davies G, Pike K, Strassle C, Allen L, Brendell R, Brownlee K, Carr S, Simmonds N, Davies Jet al., 2021, Optimising equity of access: how should we allocate slots to the most competitive trials in Cystic Fibrosis (CF)?, Journal of Cystic Fibrosis, Vol: 20, Pages: 978-985, ISSN: 1569-1993

Background:Trial participation can allow people with CF early access to CFTR modulator therapies, with high potential for clinical benefit. Therefore, the number of people wishing to participate can substantially exceed the number of slots available. We aimed to understand how the CF community thinks slots to competitive trials should be allocated across the UK and whether this should be driven by clinical need, patients’ engagement/adherence or be random. For the latter, we explored site-level versus registry-based, national randomisation processes.Methods:We developed an online survey, recruiting UK-based stakeholders through social media, newsletters and personal contacts. Closed questions were analysed for frequencies and percentages of responses. Free-text questions were analysed using thematic analysis.Results:We received 203 eligible responses. Overall, 75% of stakeholders favoured allocation of slots to individual sites based on patient population size, although pharma favoured allocation based on previous metrics. Currently, few centres have defined strategies for allocating slots locally. At face-value, stakeholders believe all eligible participants should have an equal chance of getting a slot. However, further questioning reveals preference for prioritisation strategies, primarily perceived treatment adherence, although healthcare professionals were less likely to favour this strategy than other stakeholder groups. The majority of stakeholders would prefer to allocate slots and participate in trials locally but 80% said if necessary, they would engage in a system of national allocation.Conclusions:Fair allocation to highly competitive trials does not appear to have a universally acceptable solution. Therefore, transparency and empathy remain critical to negotiate this uncertain territory.

Journal article

Castellani C, Simmonds NJ, Colombo C, Kinnman N, Desouza C, Thorat T, Chew M, Chandarana K, Van Der Ent Ket al., 2021, Respiratory microbiology outcomes from an observational study of ivacaftor in people with cystic fibrosis and non-G551D gating mutations (VOCAL), European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Dave K, Dunk R, Madge S, Gerovasili V, Reed A, Simmonds NJet al., 2021, Could a 2-year mortality prediction model have prevented deaths from respiratory failure: a single UK centre experience, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Simmonds N, Van Der Ent K, Colombo C, Kinnman N, Desouza C, Thorat T, Chandarana K, Castellani Cet al., 2021, Observational study of ivacaftor in people with cystic fibrosis and selected non-G551D gating mutations: final results from VOCAL, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

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