United Kingdom Introduction Research Articles

Biomarkers of diffuse large B-cell lymphoma: impact on diagnosis, treatment, and prognosis

Biomarkers of diffuse large B-cell lymphoma: impact on diagnosis, treatment, and prognosis Rita Coutinho, John GribbenCentre for Haemato-Onocology, Barts Cancer Institute, Queen Mary, University of London, London, United KingdomAbstract: Introduction of immunochemotherapy as frontline treatment for diffuse large B-cell lymphoma (DLBCL) has significantly increased survival. However, patients refractory to rituximab-containing regimens have a very poor survival. These differences in clinical behavior might lie behind the biological heterogeneity well recognized in this disease. Advanced molecular research has helped us to define DLBCL subgroups which harbor distinct oncogenic events and response to immunochemotherapy. The field of biomarker discovery in DLBCL has become more complex over the last decade and a broad up-to-date review on this topic is lacking. The aim for this review was to offer the hematology community a comprehensive overview of clinical and biological markers which have a diagnostic and prognostic potential and that might be amenable to therapeutic targeting. Some well known markers are reassessed in light of recent findings.Keywords: DLBCL, immunochemotherapy, rituximab, biomarkers

Development of a monoclonal antibody against the canine CCR2 as a new targeted anticancer therapy in the scope of comparative oncology

Event Abstract Back to Event Development of a monoclonal antibody against the canine CCR2 as a new targeted anticancer therapy in the scope of comparative oncology Teresa P. Raposo1*, David J. Argyle2, Breno C. Beirao2, Justina Prada1, Isabel Pires1 and Felisbina L. Queiroga1 1 University of Trás-os-Montes and Alto Douro, Department of Veterinary Sciences, Portugal 2 University of Edinburgh, The Royal (Dick) School of Veterinary Studies and The Roslin Institute, United Kingdom Introduction: In this project, it is proposed that the clinical application of a monoclonal antibody against the receptor of the Monocyte Chemotactic Protein-1 (MAb anti-CCR2), would hinder cancer progression, inhibiting macrophages recruitment. Canine mammary tumour (CMT) will be used as a model of human breast cancer, in face of molecular, histologic and clinical similarities of the disease in both species. Herein, the initial stages of the production of a MAb anti-CCR2 are described, aiming the future clinical application. Material and Methods: RNA was extracted from canine bone marrow, CCR2 cDNA was synthesized by RT-PCR, cloned into a plasmid vector, and then confirmed through DNA sequencing. TransformedBL21 DE3 E.coli were used as a system of bacterial expression. The bacterial lysates were purified through an affinity chromatography column, to isolate the CCR2 protein which was subsequently verified through mass spectrometry. Results: The purity of the isolated protein was confirmed by mass spectrometry analysis and it is now suitable for the mice immunisation. Throughout the purification process, the inclusion of urea in the lysis, wash and elution buffers was crucial to withdraw the most of the protein from the bacterial lysates. Conclusion: Hitherto, the antigen production stage was concluded, obtaining a pure form of CCR2, ready for the immunisation of mice.Hence, it is now possible to progress to the following phases in the development of a Mab anti-CCR2 using hybridoma technology. Afterwards, an experimental therapy delivering anti-CCR2 monoclonal antibody to the tumour site will be applied to dogs with advanced CMT. Acknowledgements Ministry of Science and Education, Portugal: QREN - POPH - FCT Project: SFRH / BD / 79158 / 2011 Keywords: tumour-associated macrophages, TAMs, canine cancer model, CCR2 antibody, MAb technology Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Raposo TP, Argyle DJ, Beirao BC, Prada J, Pires I and Queiroga FL (2013). Development of a monoclonal antibody against the canine CCR2 as a new targeted anticancer therapy in the scope of comparative oncology. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00269 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Miss. Teresa P Raposo, University of Trás-os-Montes and Alto Douro, Department of Veterinary Sciences, Vila Real, Portugal, rapteresa@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Teresa P Raposo David J Argyle Breno C Beirao Justina Prada Isabel Pires Felisbina L Queiroga Google Teresa P Raposo David J Argyle Breno C Beirao Justina Prada Isabel Pires Felisbina L Queiroga Google Scholar Teresa P Raposo David J Argyle Breno C Beirao Justina Prada Isabel Pires Felisbina L Queiroga PubMed Teresa P Raposo David J Argyle Breno C Beirao Justina Prada Isabel Pires Felisbina L Queiroga Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

P7. A multidisciplinary onco-plastic approach for management of chest wall tumours

P7. A multidisciplinary onco-plastic approach for management of chest wall tumours

CLIN-NEURO-COGNITIVE

CLIN-NEURO-COGNITIVE NC-02. ASSESSING NEURO-COGNITIVE STATUS IN NEWLY PRESENTING PATIENTS WITH SUPRATENTORIAL INTRACRANIAL TUMOURS. Jennifer L. Scotland1, Ian R. Whittle1, and Ian J. Deary2; University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, Dept. of Psychology, University of Edinburgh, Edinburgh, United Kingdom INTRODUCTION: Neurocognitive endpoints are increasingly included in clinical trials in neuro-oncological settings (Meyers & Brown, 2006). There is a need to identify short, repeatable measures of cognition that are sensitive to impairment in this group. Previous authors have proposed such batteries. METHODS: Newly presenting patients with a radiological diagnosis of any intracranial tumour (n 1⁄4 118) were assessed, prior to any surgical intervention, on a number of standardised cognitive and other measures as part of a larger study (Scotland et al., 2012). Their performance was compared with that of patients admitted for elective spinal surgery (n 1⁄4 85) and a healthy control group (n 1⁄4 80). RESULTS: Analysis of covariance compared the performance of the three groups. Age, sex, and National Adult Reading Test score (used to assess premorbid function) were the covariates. Patients with intracranial tumours performed significantly worse on the majority of the tests. The intracranial tumour cohort had significantly lower scores than did the spinal surgery and healthy control groups on the following measures: immediate and delayed memory (Rey Auditory Verbal Learning Test, RAVLT; p , 0.001); Trail Making Test Part B (p , 0.001); digit-symbol coding (p , 0.001); and verbal fluency (Controlled Oral Word Association Test, COWAT; p 1⁄4 0.002 and p , 0.001, respectively). There was a moderate-to-large effect size in the participant group for all tests. DISCUSSION/CONCLUSIONS: The RAVLT, Trail Making Test Part B, and COWAT are sensitive measures of cognitive impairment in patients with brain tumours and support Meyers & Brown’s (2006) proposal for the inclusion of these tests in clinical trials that have neurocognitive endpoints. The verbal fluency test, in particular, has a number of potential advantages for use in neuro-oncological settings, given that it can be completed by patients with focal motor deficits and is available in alternate forms to reduce practice effects. NC-03. A STANDARD NEUROLINGUISTIC APPROACH TO

Intervention in health care teams and working relationships

Intervention in health care teams and working relationships Mary Laurenson, Tracey Heath, Sarah GribbinUniversity of Hull, Faculty of Health and Social Care, Department of Health Professional Studies, Cottingham, Hull, United KingdomIntroduction: Communication is an intrinsic part of collaborative working but can be problematic when the complexities of professional and personal identities inhibit quality care provision. This paper investigates these complexities and recommends interventions to facilitate collaborative working.Methods: A qualitative comparative approach examined data collected from participants using purposive non-probability sampling. Perspectives were obtained from four professional groups (nurses, social workers, care managers, and police), from different organizations with different theoretical and practice frameworks, and from a fifth group (informal carers).Results: Curriculum change and leadership initiatives are required to address the complexities inhibiting collaborative working relationships. Integrating complexity theory, personality typology, and problem-based learning into the curriculum to understand behavioral actions will enable interventions to effect change and promote the centrality of those being cared for.Keywords: interprofessional education and working, complexity, communication, personality, problem-based learning

Sa1607 Endoscopic Full-Thickness Specimens of the Gastrointestinal Wall for the Detection of Neuromuscular Disease

Endoscopic Full-Thickness Specimens of the Gastrointestinal Wall for the Detection of Neuromuscular Disease Annette Fritscher-Ravens*, Mark Ellrichmann, Thilo Wedel, Klaus-GERD Hadeler, Ines Hellwig, Peter J. Milla Internal Medicine I, Interdisciplinary Endoscopy, Kiel, Germany; Anatomy, University Kiel, Kiel, Germany; Animal breeding, Loeffler Institute, Mariensee, Germany; Child Health, University College London, London, United Kingdom Introduction: Gastrointestinal (GI) neuromuscular pathology (GINMP) is associated with a broad spectrum of functional GI disorders, e.g. gastroparesis, slow-transit constipation, intestinal pseudoobstruction. Irritable bowel syndrome (IBS) is now considered to be a related disorder. Diagnosis of GINMP requires full-thickness (FT) specimens (FTS) currently accomplished by laparoscopy. Efforts to construct a device for FTS via endoscopy have not succeeded to date. Aims: 1)To test whether a novel prototype device can obtain FTS of O 1cm from the gut to enable histological analysis of GINMP; 2)to investigate for any complications and damage of adjacent tissues in the peritoneal cavity. Methods: In 30 pigs FTS were taken from the posterior gastric wall. A new modified endoscopic device using a circular cutter within an end cap mounted on the endoscope was used without electrocautery to avoid tissue damage. A metal anchor was pushed to the peritoneal side, the metal cutter pressed against it from the endoluminal side and rotation enabled sampling. The peritoneal anchor also served as abutment to avoid damage of adjacent organs and to retrieve the FTS. Endoscopic t-tags were used for closure. Mini-laparoscopy was performed to inspect the resection site for any damage caused. After 2 weeks survival, peritoneal lavage was performed prior to euthanasia and autopsy. Results: 29/30 procedures were successfully performed; 1 case of bleeding needed endoscopic treatment. All but one FTS were retrieved with the anchor in place. Time to obtain FTS was mean 8.3 min (6.0-15.5 min), for defect closure 18.5 min (range: 7.2-32 min). T-tag closure was successful in all cases. No major complications were seen. Post-procedure laparoscopy proved no other organ damage. Some very minor bleedings were seen in 6/29 cases. The size of FTS was O 9.1 mm with little evidence of edge damage. At autopsy, the scars appeared to have healed well. There was no abscess nor other abnormality. Histology and immunohistochemical work-up proved the presence of well-preserved submucosa and of both the submucosal and myenteric nerve plexus as well as intramuscular nerve fibers. The circular and longitudinal muscle layers were of very good tissue quality. The anchor pushed through the center of the FTS did not substantially alter the quality of the material. Conclusion: Using a new modified prototype endoscopic FTS-device we showed that it was possible to reliably obtain FTS in a quality that provided sufficient tissue for histological analysis of GINMP. All relevant histological and immunohistochemical techniques showed excellent staining qualities required for diagnosing the different subtypes of GINMP. The damage caused with an earlier prototype device was avoided due to the new anchor system. The improved functionality of the device might enable first studies in patients.

Differential Default Mode Network Response to Rest Cues in Adults with Attention Deficit Hyperactivity Disorder

Differential Default Mode Network Response to Rest Cues in Adults with Attention Deficit Hyperactivity Disorder

Devolution and the Shifting Political Economic Geographies of the United Kingdom Introduction and Context

Devolution and the Shifting Political Economic Geographies of the United Kingdom Introduction and Context

Mo1539 High Resolution Endoscopy in the Evaluation of Diminuitive Polyps: Does It Effect Our Diagnostic Ability?

Mo1539 High Resolution Endoscopy in the Evaluation of Diminuitive Polyps: Does It Effect Our Diagnostic Ability? Gaius R. Longcroft-Wheaton, Pradeep Bhandari Gastroenterology, Portsmouth Hospitals NHS trust, Portsmouth, United Kingdom Introduction: In recent years the resolution of endoscopes has been increasing. Modern fujinon colonoscopes have a CCD pixel density of 850,000 pixels compared to a standard definition 410,000 pixel CCD. However, acquiring high definition (HD) scopes represents a significant capital investment and their clinical value remains uncertain. This study aims to investigate the impact of high resolution endoscopy on the in-vivo histology prediction of colonic polyps Methods: Procedures were performed using fujinon colonoscopes and EPX 4400 processor. Fujinon standard definition (SD) EC 530 and high resolution (HD) EC530 and EC 590 colonoscopes were used. Polyps 10 mm were assessed using white light (WLI), FICE, and indigo carmine (IC) spray, with the predicted diagnosis recorded with each modality of imaging. In each case the kind of colonoscope (SD or HD) was recorded. Polyps were removed and sent for histological analysis, with the pathologist blinded to the diagnosis made by the endoscopist. The predicted diagnosis for WLI FICE and IC were compared to the true histology to calculate the accuracy, sensitivity and specificity of in vivo assessment using either SD or HD scopes. Mcnemear’s test was used for the statistical comparison of modalities of imaging. Results: 232 polyps 10 mm were examined, 89 polyps with standard definition endoscopes and 143 polyps high definition endoscopes. The true histology consisted of 155 neoplastic and 77 hyperplastic polyps. HD endoscopessignificantly improved the ability of the endoscopist to make an in vivo diagnosis using FICE but had no effect on the WLI or IC predicted diagnosis. See table 1. Conclusion: In-vivo diagnosis of small polyps is very important for the correct management of patients. We can conclude from our work that: 1) In-vivo prediction of polyp histology is poor with WLI and this does not improve with HD scopes2) In-vivo prediction of polyp histology is good with FICE and improves significantly with HD scopes3) In-vivo prediction of polyp histology with IC is very good and is unaffected by HD scopes

Associations between vitamin D2 and D3 and cortical bone phenotypes in childhood: a prospective cohort study

Event Abstract Back to Event Associations between vitamin D2 and D3 and cortical bone phenotypes in childhood: a prospective cohort study E Sayers1*, WD Fraser2, DA Lawlor3 and JH Tobias1 1 University of Bristol, Muscloskeletal Research Unit, United Kingdom 2 University of Liverpool, Department of Muscloskeletal Biology, United Kingdom 3 University of Bristol, MRC Centre for Causal Analyses in Translational Epidemiology, United Kingdom Introduction: Severe vitamin D deficiency, which is generally caused by reduced dietary intake and/or sun exposure, may lead to the clinical condition of osteomalacia/rickets as a result of defective skeletal mineralisation. However less is known about the consequences of milder vitamin D deficiency (insufficiency) for bone development in childhood.{BR}Methods: Using 3260 children from the Avon Longitudinal Study of Parents and Children we examined the relationship between plasma levels of 25(OH)D2 and 25(OH)D3 measured at the median age of 9.9 years, and cortical bone geometry as measured at 50% mid tibia using pQCT at a median age of 15.5 years. Analyses, which were by bootstrap linear regression, were adjusted for age, sex, body composition, social economic position and physical activity. 25(OH)D3 was seasonally adjusted. Analyses between 25(OH)D3 and cortical bone outcomes were adjusted for 25(OH)D2 and vice versa.{BR}Results: 25(OH)D2 was positively related to periosteal circumference (PC) [b=0.032 (95%CI: 0.003,0.062) p=0.03], but inversely related to cortical bone mineral density (BMDC) [b=-0.041 (95%CI: -0.073,-0.008) p=0.01] (b ~represents SD change per doubling of vitamin 25(OH)D2 or 25(OH)D3 ). 25(OH)D3 was unrelated to either of these parameters, but was instead positively related to cortical thickness, reflected by an inverse association with endosteal circumference adjusted for PC [b=-0.024 (95%CI: -0.040,-0.008) p=0.004].{BR}Differing associations of 25(OH)D2 and 25(OH)D3 with cortical bone geometry were mirrored by distinct relationships with indices of bone strength: 25(OH)D2 was associated with reduced resistance to buckling, reflected by a positive association with buckling ratio (BR) [b=0.052 (0.008,0.097) p = 0.02]; in contrast, 25(OH)D3 was associated with greater resistance to buckling, shown by a negative association with BR [b=-031 (95%CI: -0.059,-0.004), p = 0.03]. These associations of 25(OH)D2 and 25(OH)D3 with BR differed statistically (p=0.001).{BR}Conclusions: 25(OH)D2 and 25(OH)D3 levels as measured at a median of age 9.9 years had distinct relationships with cortical bone geometry as measured at age 15.5 years, and showed opposing associations with cortical bone strength. Although our results were adjusted for a range of possible confounders, residual confounding could still be responsible, or alternatively our results could reflect distinct biological actions of 25(OH)D2/D3 on cortical bone development. Keywords: Bones, Bone Research Conference: 2011 joint meeting of the Bone Research Society & the British Orthopaedic Research Society, Cambridge, United Kingdom, 27 Jun - 29 Jun, 2011. Presentation Type: Poster Topic: Abstracts Citation: Sayers E, Fraser W, Lawlor D and Tobias J (2011). Associations between vitamin D2 and D3 and cortical bone phenotypes in childhood: a prospective cohort study. Front. Endocrinol. Conference Abstract: 2011 joint meeting of the Bone Research Society & the British Orthopaedic Research Society. doi: 10.3389/conf.fendo.2011.02.00058 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Sep 2011; Published Online: 30 Sep 2011. * Correspondence: Prof. E Sayers, University of Bristol, Muscloskeletal Research Unit, United Kingdom, adrian.sayers@bristol.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers E Sayers WD Fraser DA Lawlor JH Tobias Google E Sayers WD Fraser DA Lawlor JH Tobias Google Scholar E Sayers WD Fraser DA Lawlor JH Tobias PubMed E Sayers WD Fraser DA Lawlor JH Tobias Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

HRRA1 and type VI collagen are upregulated by single impact load in a novel model of early oa in human cartilage

Event Abstract Back to Event HRRA1 and type VI collagen are upregulated by single impact load in a novel model of early oa in human cartilage FMD Henson1*, P Hernandez1, J Wardale1 and N Rushton1 1 Orthopaedic Research Unit, Department of Surgery, United Kingdom Introduction: HTRA1, a serine protease, has been shown to be upregulated in osteoarthritis (OA). It has been proposed that HTRA1 protein is upregulated as an initial event in OA which leads to breakdown of type VI collagen, an important pericellular matrix component. In order to investigate the relationship of HTRA1 and type VI collagen in the early events of human OA this work aims to i) characterise a single impact load (SIL) model of cartilage damage in human tissue and ii) describe the immunolocalisation of HTRA1 and type VI collagen in this model.{BR}Materials and Methods: 7mm full thickness cartilage discs were obtained from normal hips obtained from patients with femoral neck fractures (n=4). Cartilage was SIL with 250g from various heights, cultured for up to 10 days and processed for routine histology. Immunohistochemistry was performed using anti-HTRA1 and anti-type VI antibodies.{BR}Results: 2.5cm was chosen as the height from which SIL of 250g should be applied to mimic tissue damage seen in OA as it causes characteristic tissue damage (surface lamination, fissure formation, loss of toluidine blue and apoptosis at the surface of the cartilage). HTRA1 immunoreactivity was not present in normal cartilage at t = 0 days and was seen in the surface zone of control cartilage at 4d of culture onwards. In SIL cartilage HTRA1 was detected in the surface zone at day 1 and throughout the cartilage by day 10. Type VI collagen was detected in the surface and mid zone in control cartilage and strongly throughout the cartilage in SIL samples. HTRA1 and type VI collagen were shown to co-localise in a number of chondrocytes.{BR}Discussion: This study describes a SIL model of early OA in human cartilage. In this model it is demonstrated that HTRA1 and type VI collagen immunoreactivity is increased after SIL and culture and that the HTRA1 and type VI collagen can be co-localised. These results challenge previous findings by other workers in murine models and suggest an alternative hypothesis for the role of HTRA1 in OA. Keywords: Bones, Bone Research Conference: 2011 joint meeting of the Bone Research Society & the British Orthopaedic Research Society, Cambridge, United Kingdom, 27 Jun - 29 Jun, 2011. Presentation Type: Poster Topic: Abstracts Citation: Henson F, Hernandez P, Wardale J and Rushton N (2011). HRRA1 and type VI collagen are upregulated by single impact load in a novel model of early oa in human cartilage. Front. Endocrinol. Conference Abstract: 2011 joint meeting of the Bone Research Society & the British Orthopaedic Research Society. doi: 10.3389/conf.fendo.2011.02.00027 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Sep 2011; Published Online: 30 Sep 2011. * Correspondence: Dr. FMD Henson, Orthopaedic Research Unit, Department of Surgery, Cambridge, United Kingdom, fmdh1@cam.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers FMD Henson P Hernandez J Wardale N Rushton Google FMD Henson P Hernandez J Wardale N Rushton Google Scholar FMD Henson P Hernandez J Wardale N Rushton PubMed FMD Henson P Hernandez J Wardale N Rushton Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Direct inhibition of osteoclast formation and activity by the vitamin E isomer gamma-tocotrienol

Event Abstract Back to Event Direct inhibition of osteoclast formation and activity by the vitamin E isomer gamma-tocotrienol P Kalia1*, R Brooks1, DC Ireland1, C Beeton2 and N Rushton1 1 University of Cambridge, Orthopaedic Research Unit, Department of Surgery, United Kingdom 2 University of Cambridge, Department of Medicine, United Kingdom Introduction. Vitamin E homologues, specifically tocotrienols, have been shown to have favourable effects on bone and possess properties which suggest potential anti-resorptive activity. The hypothesis that tocopherols and/or tocotrienols might act as potential anti-resorptive agents was investigated by testing the effect of vitamin E compounds on osteoclast number, formation and resorption.{BR}Materials and Methods. Human osteoclasts were cultured on collagen, dentine and calcium phosphate substrates with or without vitamin E homologues. Compounds were either added at the start of culture to study effects on osteoclast number and formation, and at the start of osteoclastic resorption to determine effects on activity.{BR}Results and Discussion. With increasing dose of gamma-tocotrienol from 0.01 mM to 1 mM, MTS absorbance increased significantly (Figure 1, 0.01M - 0.14 ± 0.01 , 0.1mM - 0.24 ± 0.02 and 1mM - 0.67 ± 0.06; p=0.007). At 0.01 mM and 1 mM, delta-tocotrienol absorbance decreased significantly (0.05 ± 0.06 and 0, compared to 0.1 mM which had 0.17 ± 0.01; p<0.05). Comparing between the different treatment doses alpha-, delta- or gamma-tocotrienols (1 - 0.1 mM), significant differences were found depending on the dose (p=0.024, p=0.018 and p=0.007, respectively). Absorbance increased when the alpha-tocotrienol concentration was increased from 0.1 mM to 1 mM. Alpha- and gamma-tocotrienol inhibited TRAP+ osteoclast formation without reducing total cell number. A reduction in osteoclast-mediated resorption was observed after treatment with 1 and 0.1 mM delta-tocotrienol (Figure 2, 0.01 mM - 7.87 ± 3.68 %, 0.1 mM - 3.05 ± 1.20 %, 1.0 mM - 0.40 ± 0.80 %) and gamma-tocotrienol (0.01 mM - 2.60 ± 0.85 %, 0.1 mM - 2.37 ± 0.32 %, 1.0 mM - 0 %). Only gamma-tocotrienol inhibited osteoclast activity without consequent toxicity. These results were confirmed using cells from a second donor.{BR}In summary, we have identified the vitamin E isomer gamma-tocotrienol as a non-toxic, anti-resorptive compound. Gamma-tocotrienol may have potential applications in the treatment of bone loss. Keywords: Bones, Bone Research Conference: 2011 joint meeting of the Bone Research Society & the British Orthopaedic Research Society, Cambridge, United Kingdom, 27 Jun - 29 Jun, 2011. Presentation Type: Poster Topic: Abstracts Citation: Kalia P, Brooks R, Ireland D, Beeton C and Rushton N (2011). Direct inhibition of osteoclast formation and activity by the vitamin E isomer gamma-tocotrienol. Front. Endocrinol. Conference Abstract: 2011 joint meeting of the Bone Research Society & the British Orthopaedic Research Society. doi: 10.3389/conf.fendo.2011.02.00031 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Sep 2011; Published Online: 30 Sep 2011. * Correspondence: Dr. P Kalia, University of Cambridge, Orthopaedic Research Unit, Department of Surgery, United Kingdom, pk345@cam.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers P Kalia R Brooks DC Ireland C Beeton N Rushton Google P Kalia R Brooks DC Ireland C Beeton N Rushton Google Scholar P Kalia R Brooks DC Ireland C Beeton N Rushton PubMed P Kalia R Brooks DC Ireland C Beeton N Rushton Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

An audit of disabled children&amp;rsquo;s services &amp;ndash; what value is MPOC-SP?

An audit of disabled children&rsquo;s services &ndash; what value is MPOC-SP? Dawn Pickering, Monica BusseDepartment of Physiotherapy, School of Healthcare Studies, Cardiff University, Heath Park, Cardiff, Wales, United KingdomIntroduction: Achieving high standards of health care provision with children and young people with a disability requires a focus on family-centered care. There are a range of tools available to audit this type of provision. The Measure of the Processes of Care for Service Providers (MPOC-SP) is a questionnaire, which enables evaluation of family-centered care. The aim of this study was to explore staff and parental experiences of family-centered care.Method: The study utilized a mixed methodology. Quantitative data was gathered from administration of the questionnaire with staff. A series of interviews and focus groups based around the themes from the questionnaire were also conducted with staff and parents of disabled children. The questionnaire data were analyzed with SPSS v.16 for descriptive statistics. Interview and focus group data were analyzed using a template and editing approach.Results and conclusions: The mean of &lsquo;interpersonal sensitivity&rsquo; was 5.35 and &lsquo;respect&rsquo; 5.74 compared to &lsquo;providing general information&rsquo; 4.34 and &lsquo;communicating&rsquo; 4.96. Staff commented on the value of the questionnaire as a self-reflective tool. The qualitative data provided deeper insight into this area of practice. The questionnaire alone would provide limited data as part of an audit of disabled children&rsquo;s services.Keywords: childhood, disability, measurement of family-centered care

Chlorpyrifos-oxon interferes with differentiation of N2a neuroblastoma cells.

Event Abstract Back to Event Chlorpyrifos-oxon interferes with differentiation of N2a neuroblastoma cells. E Nikolaidis1, J Flaskos2, M Sachana2*, W Harris3 and A J. Hargreaves3 1 Aristotle University of Thessaloniki, Laboratory of Pharmacology, Greece 2 Aristotle University of Thessaloniki, Laboratory of Biochemistry and Toxicology, Greece 3 Nottingham Trent University, Interdisciplinary Biomedical Research Centre, United Kingdom Introduction. A rapidly growing body of data over the last decade indicates that two of the organophosphate (OP) ester pesticides, chlorpyrifos (CPF) and diazinon (DZN), are capable of inducing developmental neurotoxicity (DNT) (1). Our previous research shows that both DZN (2) and its main in vivo metabolite, diazinon-oxon (DZO) (3), inhibit neurite outgrowth, a well established in vitro biomarker of DNT (4) in N2a cells. Furthermore, we have shown that CPF also impairs neurite outgrowth in the same cellular model (5, 6). The aims of the present study were to assess the ability of the oxon in vivo metabolite of CPF, chlorpyrifos-oxon (CPO) to interfere with neurite outgrowth and to investigate the biochemical nature of any morphological effects. Methods. After 24 h exposure and induction of differentiation, N2a cells were either stained for morphological analysis or processed for SDS-PAGE and Western blotting. The blots were probed with monoclonal antibodies recognizing tubulin (B512) and GAP-43 (GAP-7B10). Results. Compared to the control, CPO, at a concentration of 10 μM, inhibited the outgrowth of neurites within 24 h. Immunoblot analysis revealed a significant decrease in reactivity with the anti-GAP-43 antibody in N2a cells treated with CPO, whereas there was no change in reactivity with the anti-α-tubulin antibody. Discussion. The results indicate that CPO causes a significant reduction in the number of neurites similarly to its parent compound (5, 6). In addition, exposure of N2a cells to CPO decreases the levels of GAP-43, an important protein in the maintenance of axons that is known to be increased during axon development. In contrast, the levels of α-tubulin are unaffected by CPO, since tubulin synthesis shows small or no specific increase during axon growth. It is inferred that the DNT which CPF causes in vivo may be partly attributed to its oxon metabolite.

Small cell lung cancer in the National Lung Cancer Audit

28 Small cell lung cancer in the National Lung Cancer Audit P. Beckett1, R.A. Stanley2, I. Woolhouse1, A. Yelland2, M.D. Peake1. 1Royal College of Physicians, London, United Kingdom, 2Information Centre for Health and Social Care, United Kingdom Introduction: The National Lung Cancer Audit is an audit of lung cancer and mesothelioma in the UK, which aims to record information about process and outcomes in lung cancer and through casemix adjustment start to explain the wide variations in outcome seen across the UK and between the UK and other Westernised countries. Methods: We have analysed all patients submitted to the Audit from English trusts with date first seen in 2008. Of 25,682 patients, 2,642 (10.3%) were confirmed to have SCLC. Results: The majority of these patients (69%) were between ages 60 79. 23% were recorded to have limited disease, 53% had extensive disease and stage data was not available in 24%. Performance status was recorded as PS 0 in 13%, PS 1 in 28%, PS 2 in 19%, PS 3 in 13% and PS 4 in 3%. Overall 63.4% were recorded to have received chemotherapy, with the proportion decreasing with increasing age and worsening PS (further details will be given in the poster). The proportion of patients having chemotherapy was 62% in extensive disease and 75% in limited disease. Comparison of the use of chemotherapy in the 30 cancer networks revealed a variation from 39% to 84% (further details to be included in poster). Conclusions: Overall, only two thirds of patients with SCLC receive chemotherapy and as expected the use of chemotherapy is related to age, PS and stage. There is a wide variation in chemotherapy use and networks with low rates of chemotherapy usage need to review their data and consider whether local guidelines and local processes need modification.

POLICY PAPER - COST Exploratory Workshop on Pharmacology and Toxicology of the Blood-Brain Barrier: State of the Art, Needs for Future Research and Expected Benefits for the EU

POLICY PAPER - COST Exploratory Workshop on Pharmacology and Toxicology of the Blood-Brain Barrier: State of the Art, Needs for Future Research and Expected Benefits for the EU

S1051 Faecal Calprotectin Home Test in Ulcerative Colitis - Is It Possible?

S1051 Faecal Calprotectin Home Test in Ulcerative Colitis - Is It Possible?

P101 - Azathioprine-associated lymphopenia in IBD – are our patients in danger? A prospective multi-centre study

s of the 4th Congress of ECCO the European Crohn’s and Colitis Organisation S51 P101 Azathioprine-associated lymphopenia in IBD are our patients in danger? A prospective multi-centre study A. Al-Rifai1, N. Prasad1 *, E. Shuttleworth2, A. Robinson2, S. Campbell1. 1Manchester Royal Infirmary, Manchester, United Kingdom, 2Salford Royal Hospital, Manchester, United Kingdom Introduction: Azathioprine (AZA) is frequently used to manage IBD patients and opportunistic infections are well documented in long-term use. Amongst non-HIV patients on immunosuppressants for other conditions, there are reports of lymphopenia (LP) related infections. LP is a recognised effect of treatment with AZA but LP related complications in IBD patients have not been widely reported. This raises the question of whether antibiotic prophylaxis is indicated for IBD patients on immunomodulators. However, there is no consensus on how to manage LP in this group. Aims: To assess the incidence of LP and any related complications in a cohort of IBD patients started on AZA. Methods: This is a prospective observational study of all patients started on AZA between 1/8/2007 and 30/9/2008 in two tertiary gastroenterology units in the UK. Data was collected on demographics, diagnosis, disease anatomy, LP episodes, relapses and concurrent therapy. LP was defined as 3 and the need for corticosteroids or anti-TNF therapy. Results: The median duration of follow-up was 51 months (10 142). Eighteen patients (12%) had a clinical recurrence within the first year following surgery before a colonoscopy was performed; 90 patients (Group C) had a systematic colonoscopy within the year following surgery (median time: 7 months, 2 13) and in 82 of them (91%), treatment was tailored according to the severity of endoscopic recurrence; 42 patients (Group NC) did not have endoscopic evaluation (8 patients declined and in 34 patients, colonoscopy was not performed in time). At time of surgery, there was no difference between Group C and Group NC except that surgery was more often curative in Group C (96%) than in Group NC (83%; p = 0.02). Time to clinical recurrence was shorter in Group NC than in Group C, with probabilities of clinical recurrence of 31% and 52% at 3 and 5 years in Group NC, and of 21% and 26% respectively in Group C (p = 0.01; logrank test). In multivariate analysis (Cox model), the following factors were associated with a higher risk of clinical recurrence: Group NC, presence of extraintestinal manifestations, and non penetrating disease behaviour. Conclusion: In our experience, the majority of patients accepts to have a colonoscopy within the year following surgery for decision of a tailored treatment. This strategy reduced clinical recurrence rate by 50% compared to absence of colonoscopy, but 12% of patients had an early recurrence before colonoscopy. P103 Mesenchymal stem cells administered via novel selective mesenteric artery cannulation for the treatment of severe refractory Crohn’s disease L. Dinesen1 *, A. Wang1, F. Vianello2, P. Tait3, E. Leen3, J. Davis2, F. Dazzi2, S. Ghosh1. 1Dept of Gastroenterology, Hammersmith Hospital, Imperial College London, United Kingdom, 2Dept of Haematology, Hammersmith Hospital, Imperial College London, United Kingdom, 3Dept of Imaging, Hammersmith Hospital, Imperial College London, United Kingdom Background: Mesenchymal stem cells (MSC) are a population of stromal origin that, in adult life, resides primarily in the bone marrow. MSC have the ability to self-renew and differentiate into tissues of mesodermal origin and produce a potent immunosuppressive effect. Recent results from multicentre clinical trials have described the successful use of MSC in severe graft-versus-host disease (GvHD), in which 60% of patients obtained complete durable remission with no toxicity. We tested their therapeutic potential in a patient with refractory Crohn’s disease. We administered MSC for the first time via selective mesenteric artery cannulation to ensure that the cells reached their target. Method: A 35 year old gentleman with severe refractory fistulizing Crohn’s disease failing all conventional therapies, biological therapies and surgical defunctioning ileostomy received mesenchymal stem cells from a haplo-identical donor, after informed consent. MSC were injected after by gest on July 1, 2016 http://eccoxfordjournals.org/ D ow nladed from

P107 - Complications and clinical outcome in chronic pouchitis patients treated with long-term antibiotic therapy

P107 - Complications and clinical outcome in chronic pouchitis patients treated with long-term antibiotic therapy

P151 - How variable is the Mayo score between observers and might this affect trial recruitment or outcome?

P151 - How variable is the Mayo score between observers and might this affect trial recruitment or outcome?