1,533 research outputs found

    Viability analysis and apoptosis induction of breast cancer cells in a microfluidic device: effect of cytostatic drugs

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    Breast cancer is the leading cause of cancer deaths among non-smoking women worldwide. At the moment the treatment regime is such that patients receive different chemotherapeutic and/or hormonal treatments dependent on the hormone receptor status, the menopausal status and age. However, in vitro sensitivity testing of tumor biopsies could rationalize and improve the choice of chemo- and hormone therapy. Lab-on-a-Chip devices, using microfluidic techniques, make detailed cellular analysis possible using fewer cells, enabling working with a patients’ own cells and performing chemo- and hormone sensitivity testing in an ex vivo setting. This article describes the development of two microfluidic devices made in poly(dimethylsiloxane) (PDMS) to validate the cell culture properties and analyze the chemosensitivity of MCF-7 cells (estrogen receptor positive human breast cancer cells) in response to the drug staurosporine (SSP). In both cases, cell viability was assessed using the life-stain Calcein-AM (CAAM) and the death dye propidium iodide (PI). MCF-7 cells could be statically cultured for up to 7 days in the microfluidic chip. A 30 min flow with SSP and a subsequent 24 h static incubation in the incubator induced apoptosis in MCF-7 cells, as shown by a disappearance of the aggregate-like morphology, a decrease in CAAM staining and an increase in PI staining. This work provides valuable leads to develop a microfluidic chip to test the chemosensitivity of tumor cells in response to therapeutics and in this way improve cancer treatment towards personalized medicine

    Excellentieonderwijs: Selectie van studenten en individuele effecten

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    Item does not contain fulltextIn de periode van medio oktober 2015 tot december 2019 hebben wij onderzoek gedaan naar de effecten van excellentieonderwijs in het Nederlandse hoger onderwijs. Dit onderzoek was onderdeel van het onderzoeksprogramma Excellentie van het Nationaal Regieorgaan Onderwijsonderzoek. In dit rapport presenteren wij twee deelstudies van het bredere onderzoek naar excellentieonderwijs, namelijk op het gebied van (1) selectie van studenten voor excellentieonderwijs, en (2) individuele effecten van deelname aan excellentieonderwijs. De andere deelstudies binnen dit bredere onderzoek (namelijk over uitstralingseffecten van excellentieonderwijs op het reguliere onderwijs en op de reguliere organisatie, en over het werkgeversperspectief op excellentieonderwijs) worden besproken in separate rapporten. Een gezamenlijke korte samenvatting over alle deelstudies binnen dit bredere onderzoek naar excellentieonderwijs wordt even-eens gepresenteerd in een afzonderlijke bijdrage.126 p

    Excellentie in het hoger onderwijs: Selectie, effectiviteit en uitstralingseffecten

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    Item does not contain fulltextIn het afgelopen decennium is binnen het hoger onderwijs in Nederland geleidelijk meer aandacht gekomen voor verschillen tussen studenten en de vraag hoe het onderwijs daarop goed kan inspelen. Door differentiatie - het bieden van variëteit in de inhoud, de vorm en het niveau - kan het onderwijs beter op studenten worden afgestemd. Excellentieonderwijs is onderwijs gericht op studenten die zich in het reguliere onderwijs te weinig uitgedaagd voelen. Hiermee wordt het vizier scherper dan voorheen gericht op studenten die meer dan gemiddeld gemotiveerd en getalenteerd zijn.13 p

    The brain-derived neurotrophic factor Val66Met polymorphism is associated with reduced functional magnetic resonance imaging activity in the hippocampus and increased use of caudate nucleus-dependent strategies in a human virtual navigation task

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    Multiple memory systems are involved in parallel processing of spatial information during navigation. A series of studies have distinguished between hippocampus-dependent ‘spatial’ navigation, which relies on knowledge of the relationship between landmarks in one’s environment to build a cognitive map, and habit-based ‘response’ learning, which requires the memorization of a series of actions and is mediated by the caudate nucleus. Studies have demonstrated that people spontaneously use one of these two alternative navigational strategies with almost equal frequency to solve a given navigation task, and that strategy correlates with functional magnetic resonance imaging (fMRI) activity and grey matter density. Although there is evidence for experience modulating grey matter in the hippocampus, genetic contributions may also play an important role in the hippocampus and caudate nucleus. Recently, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene has emerged as a possible inhibitor of hippocampal function. We have investigated the role of the BDNF Val66Met polymorphism on virtual navigation behaviour and brain activation during an fMRI navigation task. Our results demonstrate a genetic contribution to spontaneous strategies, where ‘Met’ carriers use a response strategy more frequently than individuals homozygous for the ‘Val’ allele. Additionally, we found increased hippocampal activation in the Val group relative to the Met group during performance of a virtual navigation task. Our results support the idea that the BDNF gene with the Val66Met polymorphism is a novel candidate gene involved in determining spontaneous strategies during navigation behaviour

    Competing risks survival analysis applied to data from the Australian Orthopaedic Association National Joint Replacement Registry

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    BACKGROUND AND PURPOSE: The Kaplan-Meier (KM) method is often used in the analysis of arthroplasty registry data to estimate the probability of revision after a primary procedure. In the presence of a competing risk such as death, KM is known to overestimate the probability of revision. We investigated the degree to which the risk of revision is overestimated in registry data. PATIENTS AND METHODS: We compared KM estimates of risk of revision with the cumulative incidence function (CIF), which takes account of death as a competing risk. We considered revision by (1) prosthesis type in subjects aged 75–84 years with fractured neck of femur (FNOF), (2) cement use in monoblock prostheses for FNOF, and (3) age group in patients undergoing total hip arthroplasty (THA) for osteoarthritis (OA). RESULTS: In 5,802 subjects aged 75–84 years with a monoblock prosthesis for FNOF, the estimated risk of revision at 5 years was 6.3% by KM and 4.3% by CIF, a relative difference (RD) of 46%. In 9,821 subjects of all ages receiving an Austin Moore (non-cemented) prosthesis for FNOF, the RD at 5 years was 52% and for 3,116 subjects with a Thompson (cemented) prosthesis, the RD was 79%. In 44,365 subjects with a THA for OA who were less than 70 years old, the RD was just 1.4%; for 47,430 subjects > 70 years of age, the RD was 4.6% at 5 years. INTERPRETATION: The Kaplan-Meier method substantially overestimated the risk of revision compared to estimates using competing risk methods when the risk of death was high. The bias increased with time as the incidence of the competing risk of death increased. Registries should adopt methods of analysis appropriate to the nature of their data.Marianne H. Gillam, Philip Ryan, Stephen E. Graves, Lisa N. Miller, Richard N. de Steiger and Amy Salte
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