243 research outputs found

    'Eftermaele': That Which Remains After the Event. a Panel Discussion concerning the use of video in the Documentation of Live Performance

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    An introduction to a panel discussion on the video documentation of live performance.The conference was sponsored by A.D.S.A., the Department of Performance Studies, the School of Letters, Arts and Media, and the Faculty of Arts of the University of Sydney

    New Models for Patient-specific Evaluation of the Effect of Biomaterials on Macrophages

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    Biomaterials are often used in many fields of medicine to restore or replace tissue. These biomaterials always elicit a reaction of the immune system, called the foreign body reaction, which can lead to complications in patients and failure of the device. Macrophages are key players in this reaction. Because the foreign body reaction depends on the type and consistency of biomaterials but also on the patient itself, a tailor-made model will be of great help to assess the best treatment. Therefore the ultimate aim of our research was to develop a tailor-made model. Much research has already been performed on macrophages and biomaterials, therefore we started with a literature research of what is already known. First a systematic review of in vitro models describing the macrophage polarisation (pro- (M1) or anti-inflammatory (M2)) in response to different biomaterials was performed (Chapter 2). It was found that many factors are influencing this polarisation such as chemistry, pore size and surface topography. Also sterilisation and chemically crosslinking will alter the macrophage polarisation. However, since many different culture conditions were used, it was difficult to compare the biomaterials. Since we eventually aimed for a tailor-made model, the development of an in vitro model with human isolated macrophages from blood was initiated (Chapter 3). First, distinguishing genes and cytokines for polarisation were determined. These read-out parameters were used for investigating the influence of four different biomaterials on macrophage polarisation; the model showed biomaterial-dependent differences. Macrophages on polypropylene had a phenotype comparable to M2, while macrophages on polyethylene terephthalate and on a combined biomaterial Parietex™ Composite (polyethylene terephthalate and collagen) had a phenotype similar to M1. Macrophages on a collagen biomaterial (Permacol™) produced a low amount of proteins and therefore did not have a clear phenotype. This model can be useful in the future to predict the in vivo outcome of biomaterials. Most research is performed in a sterile environment. However some anatomical locations in the human body are not sterile, like in bowel surgery or rhinoplasty as described in the case report in the introduction. The use of biomaterials in these fields has an increased risk of complications, such as infection [5]. In Chapter 4a an in vivo animal model was used in which a contaminated environment was created by puncture of the bowel, creating a peritonitis to compare the performance of different biomaterials. Six different synthetic and one biological biomaterial were implanted in the abdominal wall. Significant differences in infection rate and incorporation between materials were found. Most infections occurred in C-QurTM and Dualmesh®. The incorporation of the biological mesh (Strattice®) was less than the other synthetic biomaterials, however this mesh was never infected. Dualmesh® showed the most shrinkage. In Chapter 4b samples of the previous study were used to analyse the subtype of macrophages. Parietene CompositeTM and SeprameshTM induced more iNOS-positive cells (M1 polarisation) and C-QurTM and Dualmesh® were surrounded by more CD206-positive cells (M2 polarisation), finding biomaterial-dependent differences in this in vivo rat model. The biomaterial-dependent polarisation of macrophages in a contaminated environment in the rat study inspired to modify the culture model developed in Chapter 3. Inflammatory cytokines (LPS and IFNγ) were added to our in vitro model in Chapter 5, to mimic an inflammatory environment. Polypropylene again stimulated M2 polarisation and Parietex™ Composite and polyethylene terephthalate stimulated an M1 reaction. Despite inflammation, macrophages still behaved bThe foreign body reaction differs per biomaterial and per patient. Some patients have complications after implantation of a biomaterial and some have none with the same biomaterial. For clinical practice, it would be a great benefit to have a tailor-made model with patients own cells to test pre-operatively which biomaterial is best thereby reducing complication rates. Since most of the knowledge and use of biomaterials is in general surgery, we will focus our research in this field. The ultimate goal of our research is to develop a tailor-made _in vitro_ model with human macrophages. Towards developing this model, the following aims are formulated: 1) to develop an _in vitro_ model to study the effect of biomaterials on human macrophage polarisation 2) to investigate the influence of biomaterials on macrophage phenotype in an inflammatory environment and whether this is biomaterial-dependent 3) to investigate the influence of biomaterials on stem cells and macrophages together in an adjusted _in vitro_ mode

    The Effect of Biomaterials Used for Tissue Regeneration Purposes on Polarization of Macrophages

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    Activation of macrophages is critical in the acute phase of wound healing after implantation of surgical biomaterials. To understand the response of macrophages, they are often cultured in vitro on biomaterials. Since a wide range of biomaterials is currently used in the clinics, we undertook a systematic review of the macrophage polarization in response to these different surgical biomaterials in vitro. Beside the chemistry, material characteristics such as dimension, pore size, and surface topography are of great influence on the response of macrophages. The macrophage response also appears to depend on the differences in sterilization techniques that induce lasting biochemical changes or residues of chemicals and their byproducts used for sterilization. Regarding tissue-based biomaterials, macrophages on human or porcine dermis, strongly cross-linked by chemicals elicit in general a proinflammatory response with higher amounts of proinflammatory cytokines. Synthetic biomaterials such as polyethylene, polyethylene terephthalate (PET) + polyacrylamide (PAAm), PET + sodium salt of poly(acrylic acid) (PAANa), perfluoropolyether (PFPE) with large posts, PEG-g-PA, and polydioxanone (PDO) always appear to elicit an anti-inflammatory response in macrophages, irrespective of origin of the macrophages, for example, buffy coats or full blood. In conclusion, in general in vitro models contribute to evaluate the foreign body reaction on surgical biomaterials. Although it is difficult to simulate complexity of host response elicited by biomaterials, after their surgical implantation, an in vitro model gives indications of the initial foreign body response and allows the comparison of this response between biomaterials

    Biomaterials Influence Macrophage-Mesenchymal Stem Cell Interaction In Vitro

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    Background: Macrophages and mesenchymal stem cells (MSCs) are important cells in wound healing. We hypothesized that the cross-talk between macrophages and adipose tissue-derived MSCs (ASCs) is biomaterial dependent, thereby influencing processes involved in wound healing. Materials and Methods: The effect of macrophages cultured on polypropylene (PP) or polyethylene terephthalate coated with a collagen film (PET/Col) on ASCs in monolayer or on the same material was examined either through conditioned medium (CM) or in a direct coculture. ASC proliferation, collagen production, and gene expression were examined. As comparison, the effect of macrophages stimulated with lipopolysaccharide (LPS) and interferon gamma (IFNγ) [M(LPS/IFNγ)] or interleukin (IL) 4 [M(IL-4)] on ASCs was examined. Results: Macrophage-CM increased collagen deposition, proliferation, and gene expression of MMP1, PLOD2, and PTGS2 in ASCs, irrespective of the material. Culturing ASCs and macrophages in coculture when only macrophages were on the materials induced the same effects on gene expression. When both ASCs and macrophages were cultured on biomaterials, PP induced COL1A1 and MMP1 more than PET/Col. M(LPS/IFNγ) CM increased PLOD2, MMP1, and PTGS2 and decreased TGFB in ASCs more than the M(IL-4) CM. Conclusion: Biomaterials influence wound healing by influencing the interaction between macrophages and ASCs. We provided more insight into the behavior of different cell types during wound healing. This behavior appears to be biomaterial specific depending on which cell type interacts with the biomaterial. As such, the biomaterial will influence tissue regeneration

    Association of patients' sex with treatment outcomes after intravesical bacillus Calmette-Guérin immunotherapy for T1G3/HG bladder cancer.

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    Purpose: To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Guérin (BCG) for T1G3/HG urinary bladder cancer (UBC). Materials and methods: We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression. Results: A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78-1.60, p = 0.55). Conclusion: Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response

    RISK FACTORS FOR RESIDUAL DISEASE AT RE-TUR IN T1G3 BLADDER CANCER

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    INTRODUCTION AND OBJECTIVES: Goals of transurethral resection of a bladder tumour (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging. Persistent disease after resection of bladder tumours is not uncommon and is the reason why the European Guidelines recommended a reTUR for all T1 tumours. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival. We present here the patient and tumour factors that may influence the presence of residual disease at re-TUR. METHODS: In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 75.4% had multifocal tumours, 42.7% of tumours were more than 3 cm in diameter and 25.8% had concomitant CIS. We analyse this subgroup of patients who underwent re-TUR: there was no residual disease in 267 patients (28.6%) and residual disease in 667 patients (71.4%): Ta in 378 (40.5%) and T1 in 289 (30.9%) patients. Age, gender, tumour status (primary/recurrent), previous intravesical therapy, tumour size, tumour multi-focality, presence of concomitant CIS, and muscle in the specimen were analysed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions. RESULTS: The following were not risk factors for residual disease: age, gender, tumour status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumours, tumours > 3 cm, and presence of concomitant CISDue to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, p ¼ 0.15, while the presence of CIS only remained significant in the model with tumor size, p < 0.001. CONCLUSIONS: The most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumours and tumours more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease

    Electrical conductivity during incipient melting in the oceanic low-velocity zone

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    International audienceThe low-viscosity layer in the upper mantle, the asthenosphere, is a requirement for plate tectonics1. The seismic low velocities and the high electrical conductivities of the asthenosphere are attributed either to subsolidus, water-related defects in olivine minerals2, 3, 4 or to a few volume per cent of partial melt5, 6, 7, 8, but these two interpretations have two shortcomings. First, the amount of water stored in olivine is not expected to be higher than 50 parts per million owing to partitioning with other mantle phases9 (including pargasite amphibole at moderate temperatures10) and partial melting at high temperatures9. Second, elevated melt volume fractions are impeded by the temperatures prevailing in the asthenosphere, which are too low, and by the melt mobility, which is high and can lead to gravitational segregation11, 12. Here we determine the electrical conductivity of carbon-dioxide-rich and water-rich melts, typically produced at the onset of mantle melting. Electrical conductivity increases modestly with moderate amounts of water and carbon dioxide, but it increases drastically once the carbon dioxide content exceeds six weight per cent in the melt. Incipient melts, long-expected to prevail in the asthenosphere10, 13, 14, 15, can therefore produce high electrical conductivities there. Taking into account variable degrees of depletion of the mantle in water and carbon dioxide, and their effect on the petrology of incipient melting, we calculated conductivity profiles across the asthenosphere for various tectonic plate ages. Several electrical discontinuities are predicted and match geophysical observations in a consistent petrological and geochemical framework. In moderately aged plates (more than five million years old), incipient melts probably trigger both the seismic low velocities and the high electrical conductivities in the upper part of the asthenosphere, whereas in young plates4, where seamount volcanism occurs6, a higher degree of melting is expected
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