215 research outputs found

    Lights, camera, active! Appreciation of active learning predicts positive attitudes towards lecture capture

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    Much has been written about instructor attitudes towards lecture capture, particularly concerning political issues such as opt-out policies and the use of recordings by management. Additionally, the pedagogical concerns of lecturers have been extensively described and focus on the belief that recording lectures will impact on attendance and will reduce interactivity and active learning activities in lectures. However, little work has looked at the relationship between attitudes towards lecture capture and broader conceptions of learning and teaching. In this pre-registered study, we administered the Conceptions of Learning and Teaching scale and a novel lecture capture attitude scale to 159 higher education teachers. We found that appreciation of active learning predicted more positive attitudes towards lecture recordings as an educational support tool, whilst higher teacher-centred scores predicted greater concern about the negative educational impact of recordings. The effects observed were small; however, they are strong evidence against the view that it is instructors who value participatory and active learning that are opposed to lecture capture. Exploratory analyses also suggested that those who did not view recordings as an essential educational resource record fewer of their lectures, highlighting the real-world impact that attitudes can have, and further strengthening the need for staff to be provided with evidence-based guidance upon which to base their teaching practice. Data, analysis code, and the pre-registration are available at https://osf.io/uzs3t/

    Characterisation and radioimmunotherapy of L19-SIP, an anti-angiogenic antibody against the extra domain B of fibronectin, in colorectal tumour models

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    Angiogenesis is a characteristic feature of tumours and other disorders. The human monoclonal antibody L19- SIP targets the extra domain B of fibronectin, a marker of angiogenesis expressed in a range of tumours. The aim of this study was to investigate whole body distribution, tumour localisation and the potential of radioimmunotherapy with the L19-small immunoprotein (SIP) in colorectal tumours. Two colorectal tumour models with highly different morphologies, the SW1222 and LS174T xenografts, were used in this study. Localisation and retention of the L19-SIP antibody at tumour vessels was demonstrated using immunohistochemistry and Cy3-labelled L19-SIP. Whole body biodistribution studies in both tumour models were carried out with 125I-labelled L19-SIP. Finally, 131I-labelled antibody was used to investigate the potential of radioimmunotherapy in SW1222 tumours. Using immunohistochemistry, we confirmed extra domain B expression in the tumour vasculature. Immunofluorescence demonstrated localisation and retention of injected Cy3-labelled L19-SIP at the abluminal side of tumour vessels. Biodistribution studies using a 125I-labelled antibody showed selective tumour uptake in both models. Higher recorded values for localisation were found in the SW1222 tumours than in the LS174T (7.9 vs 6.6 %ID g−1), with comparable blood clearance for both models. Based on these results, a radioimmunotherapy study was performed in the SW1222 xenograft using 131I-Labelled L19-SIP (55.5 MBq), which showed selective tumour uptake, tumour growth inhibition and improved survival. Radio- and fluorescence-labelled L19-SIP showed selective localisation and retention at vessels of two colorectal xenografts. Furthermore, 131I-L19-SIP shows potential as a novel treatment of colorectal tumours, and provides the foundation to investigate combined therapies in the same tumour models

    Origins of the Tumor Microenvironment: Quantitative Assessment of Adipose-Derived and Bone Marrow–Derived Stroma

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    To meet the requirements for rapid tumor growth, a complex array of non-neoplastic cells are recruited to the tumor microenvironment. These cells facilitate tumor development by providing matrices, cytokines, growth factors, as well as vascular networks for nutrient and waste exchange, however their precise origins remain unclear. Through multicolored tissue transplant procedures; we have quantitatively determined the contribution of bone marrow-derived and adipose-derived cells to stromal populations within syngeneic ovarian and breast murine tumors. Our results indicate that subpopulations of tumor-associated fibroblasts (TAFs) are recruited from two distinct sources. The majority of fibroblast specific protein (FSP) positive and fibroblast activation protein (FAP) positive TAFs originate from mesenchymal stem/stromal cells (MSC) located in bone marrow sources, whereas most vascular and fibrovascular stroma (pericytes, α-SMA+ myofibroblasts, and endothelial cells) originates from neighboring adipose tissue. These results highlight the capacity for tumors to utilize multiple sources of structural cells in a systematic and discriminative manner

    Restauration morpho-dynamique et redynamisation de la section court-circuitée du Rhin en aval du barrage de Kembs (projet INTERREG / EDF)

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    National audienceThe Upper Rhine River has been heavily impacted by channelization for flood protection and navigation, and then by damming for hydropower generation. In normal non flooding conditions, most of the flows are diverted in a canalized section whereas the regulated “old Rhine” bypassed reach runs a minimum flow. Between Huningue and Neuf-Brisach, engineering works induced simplification and stabilization of the channel pattern from a formerly braiding sector to a single incised channel, hydrological modifications, bottom armouring due to bedload decrease, and thus ecological alterations. Two complementary and interdisciplinary projects have been initiated to restore alluvial morphodynamics: i) the international “INTERREG IV - Redynamisation of the old Rhine” project (2009-2012) coordinated by the Alsace region, France; ii) the left bank “controlled erosion” project launched by Electricité de France (EDF) within Kembs hydroelectric station relicensing process since 2003-2004. The purpose of these projects is to evaluate the feasibility of an important hydro-morphological and ecological restoration plan on a 45 km long reach, through both field testing of bank erosion techniques at favourable locations, and artificial sediments input from right bank excavations. This will help define possible long term prospective scenarios, in order to restore sustainable sediment transport, morphodynamics variability and associated ecological functions. The study will involve historical analysis, hydro-morphological / hydraulic physical and numerical modelling, physical and ecological monitoring, and sociological aspectsLe Rhin alsacien-allemand a enregistré de profondes modifications morphologiques et hydrologiques à la suite de sa correction et de sa régularisation pour la protection contre les crues et la navigation, puis après la construction de barrages hydro-électriques. Les aménagements réalisés entre Huningue et Neuf-Brisach ont engendré une simplification et une stabilisation du style fluvial. Un fleuve en tresses a cédé la place à un chenal unique incisé. Le fond de chenal est devenu pavé à cause d’une diminution des apports de charge de fond et des altérations écologiques ont été observées (simplification des habitats aquatiques et riverains). Deux projets complémentaires et interdisciplinaires ont été engagés afin de restaurer une dynamique des formes alluviales : i) le projet international INTERREG IV – Redynamisation du Vieux Rhin (2009-2012) sous l’impulsion de la région Alsace ; ii) le projet d’érosion maitrisée des berges de la rive gauche conduit par Electricité de France (EDF) dans le cadre du renouvellement de la concession de l’aménagement de Kembs. L’objectif des deux projets est de définir un plan de restauration hydro-morphologique et écologique conduisant à la redynamisation d’un tronçon de 45 km. L’étude repose sur une analyse historique, l’exploitation de modèles à la fois physiques et numériques, et les suivis morphologiques in situ d’une recharge artificielle en sédiments et d’érosions de berge contrôlées. Ces études de faisabilité sont complétées par des analyses écologique et sociologique pour apprécier l’impact socio-environnemental de ces projets

    Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity

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    <p>Abstract</p> <p>Background</p> <p>Tumour growth and metastatic infiltration are favoured by several components of the tumour microenvironment. Bone marrow-derived multipotent mesenchymal stromal cells (MSC) are known to contribute to the tumour stroma. When isolated from healthy bone marrow, MSC exert potent antiproliferative effects on immune effector cells. Due to phenotypic and morphological similarities of MSC and tumour stromal cells (TStrC), we speculated that immunotherapeutic approaches may be hampered if TStrC may still exhibit immunomodulatory properties of MSC.</p> <p>Methods</p> <p>In order to compare immunomodulatory properties of MSC and tumour stromal cells (TStrC), we established and analyzed TStrC cultures from eleven paediatric tumours and MSC preparations from bone marrow aspirates. Immunophenotyping, proliferation assays and NK cell cytotoxicity assays were employed to address the issue.</p> <p>Results</p> <p>While TStrC differed from MSC in terms of plasticity, they shared surface expression of CD105, CD73 and other markers used for MSC characterization. Furthermore, TStrC displayed a strong antiproliferative effect on peripheral blood mononuclear cells (PBMC) in coculture experiments similar to MSC. NK cell cytotoxicity was significantly impaired after co-culture with TStrC and expression of the activating NK cell receptors NKp44 and NKp46 was reduced.</p> <p>Conclusions</p> <p>Our data show that TStrC and MSC share important phenotypic and functional characteristics. The inhibitory effect of TStrC on PBMC and especially on NK cells may facilitate the immune evasion of paediatric tumours.</p

    The direction of research into visual disability and quality of life in glaucoma

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    <p>Abstract</p> <p>Background</p> <p>Glaucoma will undoubtedly impact on a person's ability to function as they go about their day-to-day life. The purpose of this study is to investigate the amount of published knowledge in quality of life (QoL) and visual disability studies for glaucoma, and make comparisons with similar research in other chronic conditions.</p> <p>Methods</p> <p>A systematic literature search of the Global Health, EMBASE Psychiatry and MEDLINE databases. Title searches for glaucoma and six other example chronic diseases were entered alongside a selection of keywords chosen to capture studies focusing on QoL and everyday task ability. These results were further filtered during a manual search of resulting abstracts. Outcomes were the number of publications per year for each disease, number relating to QoL and type of glaucoma QoL research.</p> <p>Results</p> <p>Fifteen years ago there were no published studies relating to the impact of glaucoma on QoL but by 2009 this had risen to 1.2% of all glaucoma articles. The number of papers relating to QoL as a proportion of all papers in glaucoma in the past 10 years (0.6%) is smaller than for AMD and some other disabling chronic diseases. Most QoL studies in glaucoma (82%) involve questionnaires.</p> <p>Conclusion</p> <p>QoL studies in glaucoma are increasing in number but represent a tiny minority of the total publications in glaucoma research. There are fewer QoL articles in glaucoma compared to some other disabling chronic conditions. The majority of QoL articles in glaucoma research use questionnaires; performance-based measures of visual disability may offer an additional method of determining how the disease impacts on QoL.</p

    Human Bone Marrow Mesenchymal Stem Cells Display Anti-Cancer Activity in SCID Mice Bearing Disseminated Non-Hodgkin's Lymphoma Xenografts

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    Abstract BACKGROUND: Although multimodality treatment can induce high rate of remission in many subtypes of non-Hodgkin's lymphoma (NHL), significant proportions of patients relapse with incurable disease. The effect of human bone marrow (BM) mesenchymal stem cells (MSC) on tumor cell growth is controversial, and no specific information is available on the effect of BM-MSC on NHL. METHODOLOGY/PRINCIPAL FINDINGS: The effect of BM-MSC was analyzed in two in vivo models of disseminated non-Hodgkin's lymphomas with an indolent (EBV(-) Burkitt-type BJAB, median survival = 46 days) and an aggressive (EBV(+) B lymphoblastoid SKW6.4, median survival = 27 days) behavior in nude-SCID mice. Intra-peritoneal (i.p.) injection of MSC (4 days after i.p. injection of lymphoma cells) significantly increased the overall survival at an optimal MSC:lymphoma ratio of 1:10 in both xenograft models (BJAB+MSC, median survival = 58.5 days; SKW6.4+MSC, median survival = 40 days). Upon MSC injection, i.p. tumor masses developed more slowly and, at the histopathological observation, exhibited a massive stromal infiltration coupled to extensive intra-tumor necrosis. In in vitro experiments, we found that: i) MSC/lymphoma co-cultures modestly affected lymphoma cell survival and were characterized by increased release of pro-angiogenic cytokines with respect to the MSC, or lymphoma, cultures; ii) MSC induce the migration of endothelial cells in transwell assays, but promoted endothelial cell apoptosis in direct MSC/endothelial cell co-cultures. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate that BM-MSC exhibit anti-lymphoma activity in two distinct xenograft SCID mouse models of disseminated NHL

    Patient-centred measurement in ophthalmology – a paradigm shift

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    Ophthalmologists and researchers in ophthalmology understand what a rapidly evolving field ophthalmology is, and that to conduct good research it is essential to use the latest and best methods. In outcomes research, one modern initiative has been to conduct holistic measurement of outcomes inclusive of the patient's point of view; patient-centred outcome. This, of course, means including a questionnaire. However, the irony of trying to improve outcomes research by being inclusive of many measures is that the researcher may not be expert in all measures used. Certainly, few people conducting outcomes research in ophthalmology would claim to be questionnaire experts. Most tend to be experts in their ophthalmic subspecialty and probably simply choose a popular questionnaire that appears to fit their needs and think little more about it. Perhaps, unlike our own field, we assume that the field of questionnaire research is relatively stable. This is far from the case. The measurement of patient-centred outcomes with questionnaires is a rapidly evolving field. Indeed, over the last few years a paradigm shift has occurred in patient-centred measurement

    Human Bone Marrow-Derived Stem Cells Acquire Epithelial Characteristics through Fusion with Gastrointestinal Epithelial Cells

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    Bone marrow-derived mesenchymal stem cells (MSC) have the ability to differentiate into a variety of cell types and are a potential source for epithelial tissue repair. Several studies have demonstrated their ability to repopulate the gastrointestinal tract (GIT) in bone marrow transplanted patients or in animal models of gastrointestinal carcinogenesis where they were the source of epithelial cancers. However, mechanism of MSC epithelial differentiation still remains unclear and controversial with trans-differentiation or fusion events being evoked. This study aimed to investigate the ability of MSC to acquire epithelial characteristics in the particular context of the gastrointestinal epithelium and to evaluate the role of cell fusion in this process. In vitro coculture experiments were performed with three gastrointestinal epithelial cell lines and MSC originating from two patients. After an 8 day coculture, MSC expressed epithelial markers. Use of a semi-permeable insert did not reproduce this effect, suggesting importance of cell contacts. Tagged cells coculture or FISH on gender-mismatched cells revealed clearly that epithelial differentiation resulted from cellular fusion events, while expression of mesenchymal markers on fused cells decreased over time. In vivo cell xenograft in immunodeficient mice confirmed fusion of MSC with gastrointestinal epithelial cells and self-renewal abilities of these fused cells. In conclusion, our results indicate that fusion could be the predominant mechanism by which human MSC may acquire epithelial characteristics when in close contact with epithelial cells from gastrointestinal origin . These results could contribute to a better understanding of the cellular and molecular mechanisms allowing MSC engraftment into the GIT epithelium

    Tumor-Like Stem Cells Derived from Human Keloid Are Governed by the Inflammatory Niche Driven by IL-17/IL-6 Axis

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    Alterations in the stem cell niche are likely to contribute to tumorigenesis; however, the concept of niche promoted benign tumor growth remains to be explored. Here we use keloid, an exuberant fibroproliferative dermal growth unique to human skin, as a model to characterize benign tumor-like stem cells and delineate the role of their "pathological" niche in the development of the benign tumor.Subclonal assay, flow cytometric and multipotent differentiation analyses demonstrate that keloid contains a new population of stem cells, named keloid derived precursor cells (KPCs), which exhibit clonogenicity, self-renewal, distinct embryonic and mesenchymal stem cell surface markers, and multipotent differentiation. KPCs display elevated telomerase activity and an inherently upregulated proliferation capability as compared to their peripheral normal skin counterparts. A robust elevation of IL-6 and IL-17 expression in keloid is confirmed by cytokine array, western blot and ELISA analyses. The altered biological functions are tightly regulated by the inflammatory niche mediated by an autocrine/paracrine cytokine IL-17/IL-6 axis. Utilizing KPCs transplanted subcutaneously in immunocompromised mice we generate for the first time a human keloid-like tumor model that is driven by the in vivo inflammatory niche and allows testing of the anti-tumor therapeutic effect of antibodies targeting distinct niche components, specifically IL-6 and IL-17.These findings support our hypothesis that the altered niche in keloids, predominantly inflammatory, contributes to the acquirement of a benign tumor-like stem cell phenotype of KPCs characterized by the uncontrolled self-renewal and increased proliferation, supporting the rationale for in vivo modification of the "pathological" stem cell niche as a novel therapy for keloid and other mesenchymal benign tumors
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