Publications
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Scott AJ, Alexander JL, Merrifield CA, et al., 2019, International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis, Gut, Vol: 68, Pages: 1624-1632, ISSN: 0017-5749
Objective In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis.Design International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research.Results Some 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field.The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis.Conclusion Data from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer.
Mason SE, Poynter L, Takats Z, et al., 2019, Optical technologies for endoscopic real-time histologic assessment of colorectal polyps: a meta-analysis, American Journal of Gastroenterology, Vol: 114, Pages: 1219-1230, ISSN: 1572-0241
OBJECTIVES: Accurate, real-time, endoscopic risk stratification of colorectal polyps would improve decision-making and optimize clinical efficiency. Technologies to manipulate endoscopic optical outputs can be used to predict polyp histology in vivo; however, it remains unclear how accuracy has progressed and whether it is sufficient for routine clinical implementation. METHODS: A meta-analysis was conducted by searching MEDLINE, Embase, and the Cochrane Library. Studies were included if they prospectively deployed an endoscopic optical technology for real-time in vivo prediction of adenomatous colorectal polyps. Polyposis and inflammatory bowel diseases were excluded. Bayesian bivariate meta-analysis was performed, presenting 95% confidence intervals (CI). RESULTS: One hundred two studies using optical technologies on 33,123 colorectal polyps were included. Digital chromoendoscopy differentiated neoplasia (adenoma and adenocarcinoma) from benign polyps with sensitivity of 92.2% (90.6%-93.9% CI) and specificity of 84.0% (81.5%-86.3% CI), with no difference between constituent technologies (narrow-band imaging, Fuji intelligent Chromo Endoscopy, iSCAN) or with only diminutive polyps. Dye chromoendoscopy had sensitivity of 92.7% (90.1%-94.9% CI) and specificity of 86.6% (82.9%-89.9% CI), similarly unchanged for diminutive polyps. Spectral analysis of autofluorescence had sensitivity of 94.4% (84.0%-99.1% CI) and specificity of 50.9% (13.2%-88.8% CI). Endomicroscopy had sensitivity of 93.6% (85.3%-98.3% CI) and specificity of 92.5% (81.8%-98.1% CI). Computer-aided diagnosis had sensitivity of 88.9% (74.2%-96.7% CI) and specificity of 80.4% (52.6%-95.7% CI). Prediction confidence and endoscopist experience alone did not significantly improve any technology. The only subgroup to demonstrate a negative predictive value for adenoma above 90% was digital chromoendoscopy, making high confidence predictions of diminutive recto-sigmoid polyps. Chronologic meta-analyses show a
Poynter L, Mirnezami R, Galea D, et al., 2019, Network mapping of molecular biomarkers influencing radiation response in rectal cancer, Clinical Colorectal Cancer, Vol: 18, Pages: e210-e222, ISSN: 1533-0028
IntroductionPre-operative radiotherapy (RT) has an important role in the management of locally advanced rectal cancer (RC). Tumour regression following RT shows marked variability and robust molecular methods are needed with which to predict likely response. The aim of this study was to review the current published literature and employ Gene Ontology (GO) analysis to define key molecular biomarkers governing radiation response in RC.MethodsA systematic review of electronic bibliographic databases (MEDLINE, Embase) was performed for original articles published between 2000 and 2015. Biomarkers were then classified according to biological function and incorporated into a hierarchical GO tree. Both significant and non-significant results were included in the analysis. Significance was binarized based on uni- and multivariate statistics. Significance scores were calculated for each biological domain (or node), and a direct acyclic graph was generated for intuitive mapping of biological pathways and markers involved in rectal cancer radiation response.Results72 individual biomarkers, across 74 studies, were identified through review. On highest order classification, molecular biomarkers falling within the domains of response to stress, cellular metabolism and pathways inhibiting apoptosis were found to be the most influential in predicting radiosensitivity.ConclusionsHomogenising biomarker data from original articles using controlled GO terminology demonstrates that cellular mechanisms of response to radiotherapy in RC - in particular the metabolic response to radiotherapy - may hold promise in developing radiotherapeutic biomarkers with which to predict, and in the future modulate, radiation response.
Lewis J, Mason S, Paizs P, et al., 2019, THE PREOPERATIVE FAECAL LIPODOME BUT NOT MICROBIAL DIVERSITY PREDICTS POST-OPERATIVE ILEUS IN ELECTIVE COLORECTAL SURGERY, Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S1453-S1454, ISSN: 0016-5085
Hall A, Leff D, Wojdecka A, et al., 2019, Beyond the healthcare paradigm: Co-creating a new model for collaborative transdisciplinary healthcare design education
© 2019 Institution of Engineering Designers, The Design Society. All rights reserved. Although healthcare has long been a focus for design research dating from the 1960’s and Bruce Archer’s Industrial Design (Engineering) research unit, there remain very few academic programmes in the field of healthcare design and even fewer that go beyond classic user driven models. This paper reports on a unique collaboration between the Royal College of Art and Imperial College in London to develop an innovative partnership and programme structure between two diverse collaborating institutions. Moreover, the partnership has shown how new design and healthcare research methods have been used for innovative practice-based healthcare design projects. We reflect on the diverse skill sets and approaches that have evolved through collaborative teamwork between healthcare practitioners, designers and diverse disciplinary backgrounds. Our conclusions illustrate how a context driven programme provides evidence of a new ‘post-disciplinary’ mindset and explores implications for research and practice for the future of healthcare design.
Hall A, Leff D, Wojdecka A, et al., 2019, Beyond the healthcare paradigm: Co-creating a new model for collaborative transdisciplinary healthcare design education
© 2019 Institution of Engineering Designers, The Design Society. All rights reserved. Although healthcare has long been a focus for design research dating from the 1960’s and Bruce Archer’s Industrial Design (Engineering) research unit, there remain very few academic programmes in the field of healthcare design and even fewer that go beyond classic user driven models. This paper reports on a unique collaboration between the Royal College of Art and Imperial College in London to develop an innovative partnership and programme structure between two diverse collaborating institutions. Moreover, the partnership has shown how new design and healthcare research methods have been used for innovative practice-based healthcare design projects. We reflect on the diverse skill sets and approaches that have evolved through collaborative teamwork between healthcare practitioners, designers and diverse disciplinary backgrounds. Our conclusions illustrate how a context driven programme provides evidence of a new ‘post-disciplinary’ mindset and explores implications for research and practice for the future of healthcare design.
Hall A, Leff D, Wojdecka A, et al., 2019, Beyond the healthcare paradigm: Co-creating a new model for collaborative transdisciplinary healthcare design education
Although healthcare has long been a focus for design research dating from the 1960’s and Bruce Archer’s Industrial Design (Engineering) research unit, there remain very few academic programmes in the field of healthcare design and even fewer that go beyond classic user driven models. This paper reports on a unique collaboration between the Royal College of Art and Imperial College in London to develop an innovative partnership and programme structure between two diverse collaborating institutions. Moreover, the partnership has shown how new design and healthcare research methods have been used for innovative practice-based healthcare design projects. We reflect on the diverse skill sets and approaches that have evolved through collaborative teamwork between healthcare practitioners, designers and diverse disciplinary backgrounds. Our conclusions illustrate how a context driven programme provides evidence of a new ‘post-disciplinary’ mindset and explores implications for research and practice for the future of healthcare design.
Hall A, Leff D, Wojdecka A, et al., 2019, BEYOND THE HEALTHCARE PARADIGM: CO-CREATING A NEW MODEL FOR COLLABORATIVE TRANSDISCIPLINARY HEALTHCARE DESIGN EDUCATION, 21st International Conference on Engineering and Product Design Education (E and PDE), Publisher: DESIGN SOC
Kinross JM, 2019, Metabolic Phenotyping in Clinical Practice, HANDBOOK OF METABOLIC PHENOTYPING, Editors: Lindon, Nicholson, Holmes, Publisher: ELSEVIER SCIENCE BV, Pages: 461-489, ISBN: 978-0-12-812293-8
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Kinross JM, 2018, Precision gaming for health: Computer games as digital medicine, METHODS, Vol: 151, Pages: 28-33, ISSN: 1046-2023
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Jitsumura M, Cunningham AL, Hitchings MD, et al., 2018, Protocol for faecal microbiota transplantation in ulcerative colitis (FMTUC): a randomised feasibility study, BMJ Open, Vol: 8, ISSN: 2044-6055
Background The interaction of the gut microbiota with the human host is implicated in the pathogenesis of inflammatory and immunological diseases including ulcerative colitis (UC). Faecal microbiota transplantation (FMT) as a method of restoring gut microbial diversity is of increasing interest as a therapeutic approach in the management of UC. The current literature lacks consensus about the dose of FMT, route of administration and duration of response.Methods and analysis This single-blinded randomised trial will explore the feasibility of FMT in 30 treatment-naïve patients with histologically confirmed distal UC limited to the recto-sigmoid region (up to 40 cm from the anal verge). This study aims to estimate the magnitude of treatment response to FMT under controlled conditions. The intervention (FMT) will be administered by rectal retention enema. It will test the feasibility of randomising patients to: (i) single FMT dose, (ii) five daily FMT doses or (iii) control (no FMT dose). All groups will receive standard antibiotic gut decontamination and bowel preparation before FMT. Recruitment will take place over a 24-month period with a 12-week patient follow-up. Trial objectives include evaluation of the magnitude of treatment response to FMT, investigation of the clinical value of metabolic phenotyping for predicting the clinical response to FMT and testing the recruitment rate of donors and patients for a study in FMT. This feasibility trial will enable an estimate of number of patients needed, help determine optimal study conditions and inform the choice of endpoints for a future definitive phase III study.Ethics and dissemination The trial is approved by the regional ethics committee and is sponsored by Abertawe Bro Morgannwg University’s Health Board. Written informed consent from all patients will be obtained. Serious adverse events will be reported to the sponsor. Trial results will be disseminated via peer review publication and shared w
Alexander J, 2018, The iKnife: Development and Clinical Applications of Rapid Evaporative Ionization Mass Spectrometry, The Handbook of Metabolic Phenotyping, Publisher: Elsevier, ISBN: 9780128122938
The Handbook of Metabolic Phenotyping is the definitive work on the rapidly developing subject of metabolic phenotyping.
Pouncey AL, Scott AJ, Alexander JL, et al., 2018, Gut microbiota, chemotherapy and the host: the influence of the gut microbiota on cancer treatment, Ecancermedicalscience, Vol: 12, ISSN: 1754-6605
The gut microbiota exists in a dynamic balance between symbiosis and pathogenesis and can influence almost any aspect of host physiology. Growing evidence suggests that the gut microbiota not only plays a key role in carcinogenesis but also influences the efficacy and toxicity of anticancer therapy. The microbiota modulates the host response to chemotherapy via numerous mechanisms, including immunomodulation, xenometabolism and alteration of community structure. Furthermore, exploitation of the microbiota offers opportunities for the personalisation of chemotherapeutic regimens and the development of novel therapies. In this article, we explore the host-chemotherapeutic microbiota axis, from basic science to clinical research, and describe how it may change the face of cancer treatment.
Alexander JL, Scott AJ, Pouncey AL, et al., 2018, Colorectal carcinogenesis: an archetype of gut microbiota-host interaction, Ecancermedicalscience, Vol: 12, ISSN: 1754-6605
Sporadic colorectal cancer (CRC) remains a major cause of worldwide mortality. Epidemiological evidence of markedly increased risk in populations that migrate to Western countries, or adopt their lifestyle, suggests that CRC is a disease whose aetiology is defined primarily by interactions between the host and his environment. The gut microbiome sits directly at this interface and is now increasingly recognised as a modulator of colorectal carcinogenesis. Bacteria such as Fusobacterium nucleatum and Escherichia coli (E. Coli) are found in abundance in patients with CRC and have been shown in experimental studies to promote neoplasia. A whole armamentarium of bacteria-derived oncogenic mechanisms has been defined, including the subversion of apoptosis and the production of genotoxins and pro-inflammatory factors. But the microbiota may also be protective: for example, they are implicated in the metabolism of dietary fibre to produce butyrate, a short chain fatty acid, which is anti-inflammatory and anti-carcinogenic. Indeed, although our understanding of this immensely complex, highly individualised and multi-faceted relationship is expanding rapidly, many questions remain: Can we define friends and foes, and drivers and passengers? What are the critical functions of the microbiota in the context of colorectal neoplasia?
Huq T, Alexander J, Cameron S, et al., 2018, Automated high-throughput colorectal cancer biomarker screening using Rapid Evaporative Ionisation Mass Spectrometry (REIMS), International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland, Publisher: WILEY, Pages: 21-21, ISSN: 0007-1323
O'Keefe S, Wilson A, Koller K, et al., 2018, Changes in the composition and activity of the colonic microbiome that may explain the extreme risk of colon cancer in Alaskan Native People., 10th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, Publisher: AMER ASSOC CANCER RESEARCH, Pages: 28-28, ISSN: 1055-9965
Poynter LR, Mirnezami R, Soares R, et al., 2018, Modulation of cellular phospholipids correlates with tumor regression grade and radio resistance in rectal cancer, Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Paizs P, Manoli E, Mason SE, et al., 2018, Rapid evaporative ionization mass spectrometry (REIMS) analysis of the mucosal lipidome has a high diagnostic accuracy for adenomas and early colorectal cancer, Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Martin G, Ghafur S, Kinross J, et al., 2018, WannaCry-a year on, BMJ: British Medical Journal, Vol: 361, ISSN: 0959-8138
Mansukhani S, Davidson M, Gillbanks A, et al., 2018, Iconic: Peri-operative immuno-chemotherapy in operable oesophageal and gastric cancer., Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
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Alexander JL, Scott A, Poynter LR, et al., 2018, Sa1840 - The colorectal cancer mucosal microbiome is defined by disease stage and the tumour metabonome, Digestive Disease Week 2018, Publisher: Elsevier, Pages: S415-S415, ISSN: 0016-5085
Mason S, Alexander JL, White E, et al., 2018, PROSPECTIVE OBSERVATIONAL COHORT STUDY OF RAPID IONIZATION MASS SPECTROMETRY (REIMS) FOR NEAR-REAL TIME DIAGNOSIS AND STRATIFICATION OF COLORECTAL CANCER, Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy / Digestive Disease Week, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S277-S278, ISSN: 0016-5085
Alexander JL, Scott A, Poynter LR, et al., 2018, THE EFFECT OF BOWEL PURGATIVE MEDICATION ON THE MUCOSA-ASSOCIATED MICROBIOTA MAY BE LESS SIGNIFICANT THAN WE THOUGHT, Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy / Digestive Disease Week, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S1044-S1045, ISSN: 0016-5085
Kinross JM, Li JV, Ocvirk S, et al., 2018, METABOLIC PHENOTYPING OF AFRICAN AND ALASKAN INDIGENOUS POPULATIONS DEMONSTRATES THAT URBANIZATION MODIFIES GUT MICROBIOME METABOLIC FUNCTIONS ASSOCIATED WITH COLON CANCER RISK, Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy / Digestive Disease Week, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S422-S422, ISSN: 0016-5085
Alexander JL, Scott A, Poynter LR, et al., 2018, THE COLORECTAL CANCER MUCOSAL MICROBIOME IS DEFINED BY DISEASE STAGE AND THE TUMOUR METABONOME, Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy / Digestive Disease Week, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S415-S415, ISSN: 0016-5085
Clift AK, Kornasiewicz O, Drymousis P, et al., 2018, Goblet cell carcinomas of the appendix: rare but aggressive neoplasms with challenging management., Endocrine Connections, Vol: 7, Pages: 268-277, ISSN: 2049-3614
Goblet cell carcinomas (GCC) are a rare, aggressive sub-type of appendiceal tumours with neuroendocrine features, and controversy exists with regards to therapeutic strategy. We undertook a retrospective review of GCC patients surgically treated at two tertiary referral centres. Clinical and histopathological data were extracted from a prospectively maintained database. Survival analyses utilised Kaplan-Meier methodology. Twenty-one patients were identified (9 females). Median age at diagnosis was 55years (range 32-77). There were 3, 6 and 9 grade 1, 2 and 3 tumours, respectively. One, 10, 5 and 5 patients had stage I, II, III and IV disease at diagnosis, respectively. There were 8, 10 and 3 Tang class A, B and C tumours, respectively. Index operation was appendectomy (n=12), right hemicolectomy (n=6) or resections including appendix/right colon, omentum and the gynaecological system (n=3). Eight patients underwent completion right hemicolectomy. Surgery for recurrence included small bowel resection (n=2), debulking with peritonectomy and heated intraperitoneal chemotherapy, and hysterectomy and bilateral salpingo-oophorectomy (all n=1). Median follow-up was 30months (range 2.5-123). One-, 3- and 5-year OS was 79.4%, 60% and 60%, respectively. Mean OS (1-, 3-, and 5-year OS) for Tang class A, B and C tumours were 73.1months (85.7%, 85.7%, 51.4%), 83.7months (all 66.7%) and 28.5months (66.7%, 66.7%, not reached), respectively. Chromogranin A/B and 68Ga-DOTATATE PET/CT were not useful in follow-up, but CEA, CA 19-9, CA 125 and 18F-FDG PET/CT identified tumour recurrence. GCC must be clearly discriminated from relatively indolent appendiceal neuroendocrine neoplasms. 18F-FDG PET/CT and CEA/CA19-9/CA-125 are useful in detecting recurrence of GCC.
Scott AJ, Merrifield CA, Alexander JL, et al., 2017, Highlights from the Inaugural International Cancer Microbiome Consortium Meeting (ICMC), 5-6 September 2017, London, UK, Ecancermedicalscience, Vol: 11, ISSN: 1754-6605
The International Cancer Microbiome Consortium (ICMC) is a recently launched collaborative between academics and academic-clinicians that aims to promote microbiome research within the field of oncology, establish expert consensus and deliver education for academics and clinicians. The inaugural two-day meeting was held at the Royal Society of Medicine (RSM), London, UK, 5–6 September 2017. Microbiome and cancer experts from around the world first delivered a series of talks during an educational day and then sat for a day of roundtable discussion to debate key topics in microbiome-cancer research.Talks delivered during the educational day covered a broad range of microbiome-related topics. The potential role of the microbiome in the pathogenesis of colorectal cancer was discussed and debated in detail with experts highlighting the latest data in animal models and humans and addressing the question of causation versus association. The impact of the microbiota on other cancers—such as lung and urogenital tract—was also discussed. The microbiome represents a novel target for therapeutic manipulation in cancer and a number of talks explored how this might be realised through diet, faecal microbiota transplant and chemotherapeutics.On the second day, experts debated pre-agreed topics with the aim of producing a consensus statement with a focus on the current state of our knowledge and key gaps for further development. The panel debated the notion of a ‘healthy’ microbiome and, in turn, the concept of dysbiosis in cancer. The mechanisms of microbiota-induced carcinogenesis were discussed in detail and our current conceptual models were assessed. Experts also considered co-factors in microbiome-induced carcinogenesis to conclude that the tripartite ‘interactome’ between genetically vulnerable host, environment and the microbiome is central to our current understanding. To conclude, the roundtable discussed how the microbiome may b
Galea D, Inglese P, Cammack L, et al., 2017, Translational utility of a hierarchical classification strategy in biomolecular data analytics., Scientific Reports, Vol: 7, ISSN: 2045-2322
Hierarchical classification (HC) stratifies and classifies data from broad classes into more specific classes. Unlike commonly used data classification strategies, this enables the probabilistic prediction of unknown classes at different levels, minimizing the burden of incomplete databases. Despite these advantages, its translational application in biomedical sciences has been limited. We describe and demonstrate the implementation of a HC approach for "omics-driven" classification of 15 bacterial species at various taxonomic levels achieving 90-100% accuracy, and 9 cancer types into morphological types and 35 subtypes with 99% and 76% accuracy, respectively. Unknown bacterial species were probabilistically assigned with 100% accuracy to their respective genus or family using mass spectra (n = 284). Cancer types were predicted by mRNA data (n = 1960) for most subtypes with 95-100% accuracy. This has high relevance in clinical practice where complete datasets are difficult to compile with the continuous evolution of diseases and emergence of new strains, yet prediction of unknown classes, such as bacterial species, at upper hierarchy levels may be sufficient to initiate antimicrobial therapy. The algorithms presented here can be directly translated into clinical-use with any quantitative data, and have broad application potential, from unlabeled sample identification, to hierarchical feature selection, and discovery of new taxonomic variants.
Kinross J, Mirnezami R, Alexander J, et al., 2017, A prospective analysis of mucosal microbiome-metabonome interactions in colorectal cancer using a combined MAS 1HNMR and metataxonomic strategy, Scientific Reports, Vol: 7, ISSN: 2045-2322
Colon cancer induces a state of mucosal dysbiosis with associated niche specific changes in the gut microbiota. However, the key metabolic functions of these bacteria remain unclear. We performed a prospective observational study in patients undergoing elective surgery for colon cancer without mechanical bowel preparation (n = 18). Using 16 S rRNA gene sequencing we demonstrated that microbiota ecology appears to be cancer stage-specific and strongly associated with histological features of poor prognosis. Fusobacteria (p < 0.007) and ε- Proteobacteria (p < 0.01) were enriched on tumour when compared to adjacent normal mucosal tissue, and fusobacteria and β-Proteobacteria levels increased with advancing cancer stage (p = 0.014 and 0.002 respecitvely). Metabonomic analysis using 1H Magic Angle Spinning Nuclear Magnetic Resonsance (MAS-NMR) spectroscopy, demonstrated increased abundance of taurine, isoglutamine, choline, lactate, phenylalanine and tyrosine and decreased levels of lipids and triglycerides in tumour relative to adjacent healthy tissue. Network analysis revealed that bacteria associated with poor prognostic features were not responsible for the modification of the cancer mucosal metabonome. Thus the colon cancer mucosal microbiome evolves with cancer stage to meet the demands of cancer metabolism. Passenger microbiota may play a role in the maintenance of cancer mucosal metabolic homeostasis but these metabolic functions may not be stage specific.
Martin G, Martin P, Hankin C, et al., 2017, Cybersecurity and healthcare: how safe are we?, BMJ-British Medical Journal, Vol: 358, ISSN: 1756-1833
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