Imperial College London

DrDeborahMorris-Rosendahl

Faculty of MedicineNational Heart & Lung Institute

Honorary Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7351 8412d.morris-rosendahl

 
 
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Location

 

2091Royal BromptonRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
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123 results found

Salmasi MY, Morris-Rosendahl D, Jarral OA, Rosendahl U, Asimakopoulos G, Raja S, Aragon-Martin JA, Child A, Pepper J, Oo A, Athanasiou T, London Aortic Mechanobiology Working Groupet al., 2022, Determining the genetic contribution in patients with non-syndromic ascending thoracic aortic aneurysms: Correlation with findings from computational pathology., Int J Cardiol, Vol: 366, Pages: 1-9

OBJECTIVES: This study aims to identify the clinical utility of targeted-genetic sequencing in a cohort of patients with TAA and establish a new method for regional histological characterisation of TAA disease. METHODS: Fifty-four patients undergoing surgery for proximal TAA were recruited. EXCLUSIONS: connective tissue disease, bicuspid aortic valves, redo surgery. All patients underwent next generation sequencing (NGS) using a custom gene panel containing 63 genes previously associated with TAA on Illumina MiSeqor NextSeq550 platforms. Explanted TAA tissue was obtained en-bloc from 34/54 patients, and complete circumferential strips of TAA tissue processed into whole slides which were subsequently digitalised. Computational pathology methods were employed to quantify elastin, cellularity and collagen in six equally divided regions across the whole aneurysm circumference. RESULTS: Of 54 patients, clearly pathogenic or potentially pathogenic variants were found in 7.4%: namely LOX, PRKG1, TGFBR1 and SMAD3 genes. 55% had at least one variant of unknown significance (VUS) and seven of the VUSs were in genes with a strong disease association (category A) genes, whilst 15 were from moderate risk (category B) genes. Elastin and collagen abundance displayed high regional variation throughout the aneurysm circumference. In patients with <60% total elastin, the loss of elastin was more significant on the outer curve (38.0% vs 47.4%, p = 0.0094). The presence of VUS, higher pulse wave velocity and advancing age were predictors of elastin loss (regression analysis: p < 0.05). CONCLUSIONS: These findings demonstrate the heterogeneity of TAA disease microstructure and the potential link between histological appearance and clinical factors, including genetic variation.

Journal article

Amin R, Morris-Rosendahl D, Edwards M, Tayal U, Buchan R, Hammersley D, Jones R, Gati S, Khalique Z, Almogheer B, Pennell D, Baksi A, Pantazis A, Ware J, Prasad S, Halliday Bet al., 2022, The addition of genetic testing and cardiovascular magnetic resonance to routine clinical data for stratification of aetiology in dilated cardiomyopathy, Frontiers in Cardiovascular Medicine, ISSN: 2297-055X

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

Shoemark A, Griffin H, Wheway G, Hogg C, Lucas JS, Genomics England Research Consortium, Camps C, Taylor J, Carroll M, Loebinger MR, Chalmers JD, Morris-Rosendahl D, Mitchison HM, De Soyza Aet al., 2022, Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis., Eur Respir J

BACKGROUND: Bronchiectasis can result from infectious, genetic, immunological and allergic causes. 60-80% cases are idiopathic, but a well-recognised genetic cause is the motile ciliopathy, primary ciliary dyskinesia (PCD). Diagnosis of PCD has management implications including addressing co-morbidities, implementing genetic and fertility counselling and future access to PCD-specific treatments. Diagnostic testing can be complex, however PCD genetic testing is rapidly moving from research into clinical diagnostics and would confirm the cause of bronchiectasis. METHODS: This observational study used genetic data from severe bronchiectasis patients recruited to the UK 100,000 Genomes Project and patients referred for gene panel testing within a tertiary respiratory hospital, Patients referred for genetic testing due to clinical suspicion of PCD were excluded from both analyses. Data was accessed from the British Thoracic Society audit, to investigate whether motile ciliopathies are underdiagnosed in people with bronchiectasis in the UK. RESULTS: Pathogenic or likely pathogenic variants were identified in motile ciliopathy genes in 17/142 (12%) individuals by whole genome sequencing. Similarly in a single centre with access to pathological diagnostic facilities, 5-10% patients received a PCD diagnosis by gene panel, often linked to normal/inconclusive nasal nitric oxide and cilia functional test results. In 4,898 audited patients with bronchiectasis, <2% were tested for PCD and <1% received genetic testing. CONCLUSIONS: PCD is underdiagnosed as a cause of bronchiectasis. Increased uptake of genetic testing may help to identify bronchiectasis due to motile ciliopathies and ensure appropriate management.

Journal article

Mahmood A, Morris-Rosendahl D, Edwards M, Fleming A, Homfray T, Mason S, Quinn E, Ware J, Baksi J, Prasad S, Pantazis A, Halliday Bet al., 2022, DISEASE PENETRANCE IN ASYMPTOMATIC CARRIERS OF FAMILIAL CARDIOMYOPATHY VARIANTS, Publisher: BMJ PUBLISHING GROUP, Pages: A9-A9, ISSN: 1355-6037

Conference paper

Cockbain B, Morris-Rosendahl D, Corrigan A, Hind MDet al., 2022, COPD in the chromosomes, THORAX, Vol: 77, Pages: 731-732, ISSN: 0040-6376

Journal article

Guimier A, Achleitner MT, de Bellaing AM, Edwards M, de Pontual L, Mittal K, Dunn KE, Grove ME, Tysoe CJ, Dimartino C, Cameron J, Kanthi A, Shukla A, van den Broek F, Chatterjee D, Alston CL, V Knowles C, Brett L, Till JA, Homfray T, French P, Spentzou G, Elserafy NA, Lichkus KS, Sankaran BP, Kennedy HL, George PM, Kidd A, Wortmann SB, Fisk DG, Koopmann TT, Rafiq MA, Merker JD, Parikh S, Ahimaz P, Weintraub RG, Ma AS, Turner C, Ellaway CJ, Phillips LK, Thorburn DR, Chung WK, Kana SL, Faye-Petersen OM, Thompson ML, Janin A, McLeod K, McGowan R, McFarland R, Girisha KM, Morris-Rosendahl DJ, Hurst ACE, Turner CLS, Hamilton RM, Taylor RW, Bajolle F, Gordon CT, Amiel J, Mayr JA, Doudney Ket al., 2022, PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families (vol 23, pg 2415, 2021), GENETICS IN MEDICINE, Vol: 24, Pages: 967-967, ISSN: 1098-3600

Journal article

Nastase A, Mandal A, Lu SK, Anbunathan H, Morris-Rosendahl D, Zhang YZ, Sun X-M, Gennatas S, Rintoul RC, Edwards M, Bowman A, Chernova T, Benepal T, Lim E, Taylor AN, Nicholson AG, Popat S, Willis AE, MacFarlane M, Lathrop M, Bowcock AM, Moffatt MF, Cookson WOCMet al., 2022, Integrated genomics point to immune vulnerabilities in pleural mesothelioma (vol 11, 19138, 2021), SCIENTIFIC REPORTS, Vol: 12, ISSN: 2045-2322

Journal article

Nastase A, Mandal A, Lu SK, Abunathan H, Morris-Rosendahl D, Zhand YZ, Sun X-M, Gennatas S, Rintoul R, Edwards M, Bowman A, Chernova T, Benepal T, Lim E, Newman Taylor A, Nicholson A, Popat S, Willis A, MacFarlane M, Lathrop M, Bowcock A, Moffatt M, Cookson Wet al., 2021, Integrated genomics point to immune vulnerabilities in pleural mesothelioma, Scientific Reports, Vol: 11, ISSN: 2045-2322

Pleural mesothelioma is an aggressive malignancy with limited effective therapies. In order to identify therapeutic targets, we integrated SNP genotyping, sequencing and transcriptomics from tumours and low-passage patient-derived cells. Previously unrecognised deletions of SUFU locus (10q24.32), observed in 21% of 118 tumours, resulted in disordered expression of transcripts from Hedgehog pathways and the T-cell synapse including VISTA. Co-deletion of Interferon Type I genes and CDKN2A was present in half of tumours and was a predictor of poor survival. We also found previously unrecognised deletions in RB1 in 26% of cases and show sub-micromolar responses to downstream PLK1, CHEK1 and Aurora Kinase inhibitors in primary mesothelioma cells. Defects in Hippo pathways that included RASSF7 amplification and NF2 or LATS1/2 mutations were present in 50% of tumours and were accompanied by micromolar responses to the YAP1 inhibitor Verteporfin. Our results suggest new therapeutic avenues in mesothelioma and indicate targets and biomarkers for immunotherapy.

Journal article

Mani R, Gomes M, Gonzalez AR, Hogg C, Morris-Rosendahl D, Maitre B, Fassad MR, Goutaki M, Lucas JS, Shoemark A, Mitchison HM, Legendre M, Crowley Set al., 2021, Development and first results of the BEAT-PCD international Primary Ciliary Dyskinesia gene variant database: CiliaVar, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Guimier A, Achleitner MT, de Bellaing AM, Edwards M, de Pontual L, Mittal K, Dunn KE, Grove ME, Tysoe CJ, Dimartino C, Cameron J, Kanthi A, Shukla A, van den Broek F, Chatterjee D, Alston CL, Knowles CV, Brett L, Till JA, Homfray T, French P, Spentzou G, Elserafy NA, Lichkus KS, Sankaran BP, Kennedy HL, George PM, Kidd A, Wortmann SB, Fisk DG, Koopmann TT, Rafiq MA, Merker JD, Parikh S, Ahimaz P, Weintraub RG, Ma AS, Turner C, Ellaway CJ, Phillips LK, Thorburn DR, Chung WK, Kana SL, Faye-Petersen OM, Thompson ML, Janin A, McLeod K, McGowan R, McFarland R, Girisha KM, Morris-Rosendahl DJ, Hurst ACE, Turner CLS, Hamilton RM, Taylor RW, Bajolle F, Gordon CT, Amiel J, Mayr JA, Doudney Ket al., 2021, PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families, Genetics in Medicine, Vol: 23, Pages: 2415-2425, ISSN: 1098-3600

PurposeBiallelic hypomorphic variants in PPA2, encoding the mitochondrial inorganic pyrophosphatase 2 protein, have been recently identified in individuals presenting with sudden cardiac death, occasionally triggered by alcohol intake or a viral infection. Here we report 20 new families harboring PPA2 variants.MethodsSynthesis of clinical and molecular data concerning 34 individuals harboring five previously reported PPA2 variants and 12 novel variants, 11 of which were functionally characterized.ResultsAmong the 34 individuals, only 6 remain alive. Twenty-three died before the age of 2 years while five died between 14 and 16 years. Within these 28 cases, 15 died of sudden cardiac arrest and 13 of acute heart failure. One case was diagnosed prenatally with cardiomyopathy. Four teenagers drank alcohol before sudden cardiac arrest. Progressive neurological signs were observed in 2/6 surviving individuals. For 11 variants, recombinant PPA2 enzyme activities were significantly decreased and sensitive to temperature, compared to wild-type PPA2 enzyme activity.ConclusionWe expand the clinical and mutational spectrum associated with PPA2 dysfunction. Heart failure and sudden cardiac arrest occur at various ages with inter- and intrafamilial phenotypic variability, and presentation can include progressive neurological disease. Alcohol intake can trigger cardiac arrest and should be strictly avoided.

Journal article

Shoemark A, Rubbo B, Legendre M, Fassad MR, Haarman EG, Best S, Bon ICM, Brandsma J, Burgel P-R, Carlsson G, Carr SB, Carroll M, Edwards M, Escudier E, Honore I, Hunt D, Jouvion G, Loebinger MR, Maitre B, Morris-Rosendahl D, Papon J-F, Parsons CM, Patel MP, Thomas NS, Thouvenin G, Walker WT, Wilson R, Hogg C, Mitchison HM, Lucas JSet al., 2021, Topological data analysis reveals genotype-phenotype relationships in primary ciliary dyskinesia, EUROPEAN RESPIRATORY JOURNAL, Vol: 58, ISSN: 0903-1936

Journal article

Sepahzad A, Morris-Rosendahl D, Davies J, 2021, Cystic fibrosis lung disease modifiers and their relevance in the new era of precision medicine, Genes, Vol: 12, ISSN: 2073-4425

Our understanding of cystic fibrosis (CF) has grown exponentially since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989. With evolving genetic and genomic tools, we have come to better understand the role of CFTR genotypes in the pathophysiology of the disease. This, in turn, has paved the way for the development of modulator therapies targeted at mutations in the CFTR, which are arguably one of the greatest advances in the treatment of CF. These modulator therapies, however, do not target all the mutations in CFTR that are seen in patients with CF and, furthermore, a variation in response is seen in patients with the same genotype who are taking modulator therapies. There is growing evidence to support the role of non-CFTR modifiers, both genetic and environmental, in determining the variation seen in CF morbidity and mortality and also in the response to existing therapies. This review focusses on key findings from studies using candidate gene and genome-wide approaches to identify CF modifier genes of lung disease in cystic fibrosis and considers the interaction between modifiers and the response to modulator therapies. As the use of modulator therapies expands and we gain data around outcomes, it will be of great interest to investigate this interaction further. Going forward, it will also be crucial to better understand the relative influence of genomic versus environmental factors. With this understanding, we can truly begin to deliver personalised care by better profiling the likely disease phenotype for each patient and their response to treatment.

Journal article

Domingo-Sabugo C, Starren E, Mandal A, Nastase A, Hoang L, Edwards M, Morris-Rosendahl D, Lim E, Nicholson AG, Lathrop M, Cookson W, Moffatt Met al., 2020, Distinct Landscapes of Genomic Alterations between Lung Carcinoids and Non-Small Cell Lung Cancers, Publisher: SPRINGERNATURE, Pages: 528-528, ISSN: 1018-4813

Conference paper

Fleming AG, Brett L, Wilkinson S, John S, Briggs L, Edwards M, Morris-Rosendahl DJet al., 2020, Non-segregation of truncating TTN variants in families with dilated cardiomyopathy (DCM), Publisher: SPRINGERNATURE, Pages: 268-268, ISSN: 1018-4813

Conference paper

Vijayasingam A, Frost E, Wilkins J, Gillen L, Premachandra P, Mclaren K, Gilmartin D, Picinali L, Vidal-Diez A, Borsci S, Ni MZ, Tang WY, Morris-Rosendahl D, Harcourt J, Elston C, Simmonds NJ, Shah Aet al., 2020, Tablet and web-based audiometry to screen for hearing loss in adults with cystic fibrosis, Thorax, Vol: 75, Pages: 632-639, ISSN: 0040-6376

INTRODUCTION: Individuals with chronic lung disease (eg, cystic fibrosis (CF)) often receive antimicrobial therapy including aminoglycosides resulting in ototoxicity. Extended high-frequency audiometry has increased sensitivity for ototoxicity detection, but diagnostic audiometry in a sound-booth is costly, time-consuming and requires a trained audiologist. This cross-sectional study analysed tablet-based audiometry (Shoebox MD) performed by non-audiologists in an outpatient setting, alongside home web-based audiometry (3D Tune-In) to screen for hearing loss in adults with CF. METHODS: Hearing was analysed in 126 CF adults using validated questionnaires, a web self-hearing test (0.5 to 4 kHz), tablet (0.25 to 12 kHz) and sound-booth audiometry (0.25 to 12 kHz). A threshold of ≥25 dB hearing loss at ≥1 audiometric frequency was considered abnormal. Demographics and mitochondrial DNA sequencing were used to analyse risk factors, and accuracy and usability of hearing tests determined. RESULTS: Prevalence of hearing loss within any frequency band tested was 48%. Multivariate analysis showed age (OR 1.127; (95% CI: 1.07 to 1.18; p value<0.0001) per year older) and total intravenous antibiotic days over 10 years (OR 1.006; (95% CI: 1.002 to 1.010; p value=0.004) per further intravenous day) were significantly associated with increased risk of hearing loss. Tablet audiometry had good usability, was 93% sensitive, 88% specific with 94% negative predictive value to screen for hearing loss compared with web self-test audiometry and questionnaires which had poor sensitivity (17% and 13%, respectively). Intraclass correlation (ICC) of tablet versus sound-booth audiometry showed high correlation (ICC >0.9) at all frequencies ≥4 kHz. CONCLUSIONS: Adults with CF have a high prevalence of drug-related hearing loss and tablet-based audiometry can be a practical, accurate screening tool within integrated ototoxicity monitoring programmes for early detection.

Journal article

Morris-Rosendahl DJ, Edwards M, McDonnell MJ, John S, Alton EWFW, Davies JC, Simmonds NJet al., 2020, Whole-gene sequencing of CFTR reveals a high prevalence of the intronic variant c.3874-4522A>G in cystic fibrosis., American Journal of Respiratory and Critical Care Medicine, Vol: 201, Pages: 1438-1441, ISSN: 1073-449X

Journal article

Fassad MR, Patel MP, Shoemark A, Cullup T, Hayward J, Dixon M, Rogers A, Ollosson S, Jackson C, Goggin P, Hirst RA, Rutman A, Thompson J, Jenkins L, Aurora P, Moya E, Chetcuti P, O'Callaghan C, Morris-Rosendahl DJ, Watson CM, Wilson R, Carr S, Walker W, Pitno A, Lopes S, Morsy H, Shoman W, Pereira L, Constant C, Loebinger MR, Chung EMK, Kenia P, Rumman N, Fasseeh N, Lucas JS, Hogg C, Mitchison HMet al., 2020, Clinical utility of NGS diagnosis and disease stratification in a multiethnic primary ciliary dyskinesia cohort, JOURNAL OF MEDICAL GENETICS, Vol: 57, Pages: 322-330, ISSN: 0022-2593

Journal article

Olubando D, Hopton C, Eden J, Caswell R, Thomas N, Roberts SA, Morris-Rosendahl D, Venetucci L, Newman WGet al., 2020, Classification and correlation of RYR2 missense variants in individuals with catecholaminergic polymorphic ventricular tachycardia reveals phenotypic relationships, JOURNAL OF HUMAN GENETICS, Vol: 65, Pages: 531-539, ISSN: 1434-5161

Journal article

Morris-Rosendahl DJ, Crocq M-A, 2020, Neurodevelopmental disorders-the history and future of a diagnostic concept, DIALOGUES IN CLINICAL NEUROSCIENCE, Vol: 22, Pages: 65-72, ISSN: 1294-8322

Journal article

Rubbo B, Shoemark A, Legendre M, Fassad M, Haarman E, Best S, Bon ICM, Brandsma J, Burgel P, Carlsson G, Carr S, Carroll M, Edwards M, Escudier E, Honore I, Hunt D, Jouvion G, Loebinger MR, Maitre BM, Morris-Rosendahl D, Papon J, Parsons C, Patel MP, Thomas S, Thouvenin G, Walker WT, Wilson R, Hogg C, Mitchison HM, Lucas JSet al., 2020, Topological Data Analysis Coupled with Machine Learning Reveals New Genotype-Phenotype Relationships in Primary Ciliary Dyskinesia, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Yazdani MF, Morris-Rosendahl D, Chen L, Devaraj A, Chua Fet al., 2020, Images of the month 1: Cough before the storm: A case of pulmonary alveolar microlithiasis, Clinical Medicine, Vol: 20, Pages: 110-111, ISSN: 1470-2118

Journal article

Shovlin CL, Morris-Rosendahl DJ, Copeland F, De Soyza A, Hogg C, Jenkins G, Marciniak SJ, Lovett M, Moffatt MF, Cookson WOC, Alikian M, Hasan S, Slade R, Xiao S, Boardman-Pretty F, Brown D, Caulfield M, Devereau A, Fowler T, McDonagh E, Scott R, Thomas ERA, Alton EWFWet al., 2019, DELIVERING THE 100,000 GENOMES PROJECT TO ESTABLISH THE FUNCTIONAL ROLE OF DNA SEQUENCE VARIANTS IN RESPIRATORY RARE DISEASES, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A44-A45, ISSN: 0040-6376

Conference paper

Wallmeier J, Frank D, Shoemark A, Noethe-Menchen T, Cindric S, Olbrich H, Loges NT, Aprea I, Dougherty GW, Pennekamp P, Kaiser T, Mitchison HM, Hogg C, Carr SB, Zariwala MA, Ferkol T, Leigh MW, Davis SD, Atkinson J, Dutcher SK, Knowles MR, Thiele H, Altmueller J, Krenz H, Woeste M, Brentrup A, Ahrens F, Vogelberg C, Morris-Rosendahl DJ, Omran Het al., 2019, De novo mutations in FOXJ1 result in a motile ciliopathy with hydrocephalus and randomization of left/right body asymmetry, American Journal of Human Genetics, Vol: 105, Pages: 1030-1039, ISSN: 0002-9297

Journal article

Hoang L, Domingo-Sabugo C, Starren E, Willis-Owen S, Nicholson A, Morris-Rosendahl D, Moffatt M, Cookson Wet al., 2019, Integrative Omics Analysis Reveals Important Roles of Adenosine Diphosphate in Haemostasis and Platelet Activation in NSCLC, Publisher: ELSEVIER SCIENCE INC, Pages: S419-S419, ISSN: 1556-0864

Conference paper

Mandal A, Nastase A, Lu SK, Gennatas S, Anbunathan H, Edwards M, Morris-Rosendahl D, Taylor AN, Rintoul RC, Lim E, Popat S, Nicholson A, Bowcock A, Lathrop M, Moffatt M, Cookson Wet al., 2019, Analysis of Immune Phenotype Composition in Malignant Pleural Mesothelioma (MPM) Using Bulk RNA Sequencing, Publisher: ELSEVIER SCIENCE INC, Pages: S345-S346, ISSN: 1556-0864

Conference paper

Domingo-Sabugo C, Starren E, Mandal A, Nastase A, Hoang L, Edwards M, Morris-Rosendahl D, Lim E, Nicholson A, Lathrop M, Cookson W, Moffatt Met al., 2019, Comprehensive Molecular Profiling and Comparison of Common and Rarer Subtypes of Lung Cancer, Publisher: ELSEVIER SCIENCE INC, Pages: S686-S686, ISSN: 1556-0864

Conference paper

Wilkinson SL, Edwards M, John S, Honti F, Mackintosh J, Morris-Rosendahl DJet al., 2019, Complex indel variant calling in a repetitive genomic region, 52nd Conference of the European-Society-of-Human-Genetics (ESHG), Publisher: NATURE PUBLISHING GROUP, Pages: 1255-1256, ISSN: 1018-4813

Conference paper

Nastase A, Mandal A, Lu SK, Gennatas S, Anbunathan H, Edwards M, Morris-Rosendahl D, Taylor AN, Rintoul RC, Lim E, Popat S, Nicholson A, Lathrop M, Bowcock A, Moffatt M, Cookson Wet al., 2019, Low Number of Mutations and Frequent Co-Deletions of CDKN2A and IFN Type I Characterize Malignant Pleural Mesothelioma, Publisher: ELSEVIER SCIENCE INC, Pages: S345-S345, ISSN: 1556-0864

Conference paper

Edwards M, Wilkinson S, van den Broek F, Brett L, Till J, Mayr JA, Homfray T, Morris-Rosendahl Det al., 2019, Sudden cardiac death caused by bi-allelic variants in the PPA2 gene, 51st Conference of the European-Society-of-Human-Genetics (ESHG) in conjunction with the European Meeting on Psychosocial Aspects of Genetics (EMPAG), Publisher: NATURE PUBLISHING GROUP, Pages: 161-161, ISSN: 1018-4813

Conference paper

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