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Lancashire, United Kingdom

Kelly J.G.,Lancaster University | Trevisan J.,Lancaster University | Scott A.D.,Colworth Science Park | Carmichael P.L.,Colworth Science Park | And 3 more authors.
Journal of Proteome Research | Year: 2011

Biospectroscopy is employed to derive absorbance spectra representative of biomolecules present in biological samples. The mid-infrared region (λ = 2.5 μm-25 μm) is absorbed to give a biochemical-cell fingerprint (ṽ = 1800-900 cm-1). Cellular material produces complex spectra due to the variety of chemical bonds present. The complexity and size of spectral data sets warrant multivariate analysis for data reduction, interpretation, and classification. Various multivariate analyses are available including principal component analysis (PCA), partial least-squares (PLS), linear discriminant analysis (LDA), and evolving fuzzy rule-based classifier (eClass). Interpretation of both visual and numerical results facilitates biomarker identification, cell-type discrimination, and predictive and mechanistic understanding of cellular behavior. Biospectroscopy is a high-throughput nondestructive technology. A comparison of biomarkers/mechanistic knowledge determined from conventional approaches to biospectroscopy coupled with multivariate analysis often provides complementary answers and a novel approach for diagnosis of disease and cell biology. © 2011 American Chemical Society. Source


Nagy E.,Kings College London | Gajjar K.B.,Lancaster University | Patel I.I.,University of Cambridge | Taylor S.,Liverpool Womens Hospital NHS Foundation Trust | And 4 more authors.
British Journal of Cancer | Year: 2014

Background:Tamoxifen has anti-oestrogenic and anti-tumour activity in the breast, but is oestrogenic and carcinogenic in the endometrium. It can induce experimental tumours by both hormonal and DNA-damaging mechanisms, but its carcinogenic mode of action in human endometrium remains unclear.Methods:We investigated whether an epigenetic mechanism, involving promoter hypermethylation of the gene for the DNA repair enzyme MGMT (O6-methylguanine DNA methyltransferase), was associated with K-RAS, TP53 and PTEN mutations in endometrial tumours from women treated with tamoxifen (TAM, n=30) or unexposed to the drug (EC, n=38).Results:There were significant (P<0.05) differences in tumour grade between the TAM and EC groups, with more favourable morphology in the latter. K-RAS mutations, predominantly G>A, occurred in small numbers in both groups. TP53 mutations were of mainly A>G, C>T and indel modifications in both groups, but more frequent in TAM cases. PTEN mutations dominated in EC tumours and were of the type that has large impact on protein function, such as indel or nonsense mutations. These observations alongside the mutational spectrum in PTEN suggest that the malignancies arise from different backgrounds, hence pointing to an effect of tamoxifen. Both groups displayed MGMT promoter hypermethylation. This coincided with mutations more frequently in the TAM (78%) than in the EC (50%) group, even though there were significantly (P<0.05) fewer mutations and methylations in TAM cases.Conclusions:Although the difference in coincidence did not reach significance with the current sample size, the findings suggest that epigenetic processes may play a role in the way tamoxifen induces endometrial cancer. © 2014 Cancer Research UK. Source


Rutherford C.L.,Lancashire Teaching Hospitals NHS Trust
BMJ case reports | Year: 2013

A woman in her early 50s presented with a 2-week history of gradually worsening colicky abdominal pain with associated vomiting, loose stools and reduced appetite. There was no malaena or perrectal bleeding. On examination, there was tenderness in the epigastric region with an associated palpable fullness. Subsequent imaging revealed a substantial colo-colic intussusception with the lead point being a lipoma of the ascending colon. Subsequent colonic resection was undertaken with histology confirming a lipomatous polyp. Source


Anwar S.,Calderdale and Huddersfield NHS Trust | Peter M.B.,Calderdale and Huddersfield NHS Trust | Dent J.,Calderdale and Huddersfield NHS Trust | Scott N.A.,Lancashire Teaching Hospitals NHS Trust
Colorectal Disease | Year: 2012

Aim Patients with stage IV colorectal cancer with unresectable metastases can either receive chemotherapy or palliative resection of the primary lesion. In the absence of any randomized data the choice of initial treatment in stage IV colorectal cancer is not based on firm evidence. Method A search of MEDLINE, Pubmed, Embase and the Cochrane Library database was performed from 1980 to 2010 for studies comparing palliative resection in stage IV colorectal cancer with other treatment modalities. Audits and observational studies were excluded. Median survival was the primary outcome measure. The morbidity and mortality of surgical and nonsurgical treatments were compared. Results Twenty-one studies (no randomized controlled trials) were identified. Most demonstrated a survival benefit for patients who underwent palliative resection. Multivariate analysis indicates that tumour burden and performance status are both major independent prognostic variables. Selection bias, incomplete follow up and nonstandardized reporting of complications make the data difficult to interpret. Conclusion The studies indicate that there may be a survival benefit for primary resection of colorectal cancer in stage IV disease. The findings suggest that resection of the primary tumour should be based on tumour burden and performance status rather than on the presence or absence of symptoms alone. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland. Source


Gaunt K.,Lancashire Teaching Hospitals NHS Trust | Ramachandran S.,Lancashire Teaching Hospitals NHS Trust | Pushkar P.,Aintree University Hospitals Trust
Medical Teacher | Year: 2013

The organisation, administration and running of a successful OSCE programme need considerable knowledge, experience and planning. Different teams looking after various aspects of OSCE need to work collaboratively for an effective question bank development, examiner training and standardised patients' training. Quality assurance is an ongoing process taking place throughout the OSCE cycle. In order for the OSCE to generate reliable results it is essential to pay attention to each and every element of quality assurance, as poorly standardised patients, untrained examiners, poor quality questions and inappropriate scoring rubrics each will affect the reliability of the OSCE. The validity will also be influenced if the questions are not realistic and mapped against the learning outcomes of the teaching programme. This part of the Guide addresses all these important issues in order to help the reader setup and quality assure their new or existing OSCE programmes. © 2013 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted. Source

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