1,154 research outputs found

    A Multimodal Approach to the Management of Neuroendocrine Tumour Liver Metastases

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    Neuroendocrine tumours (NETs) are often indolent malignancies that commonly present with metastatic disease in the liver. Surgical, locoregional, and systemic treatment modalities are reviewed. A multidisciplinary approach to patient care is suggested to ensure all therapeutic options explored

    Dowelled structural connections in laminated bamboo and timber

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    © 2016 The Authors. Structural sections of laminated bamboo can be connected using methods common in timber engineering, however the different material properties of timber and laminated bamboo suggest that the behaviour of connections in the two materials would not be the same. This study investigates the dowelled connection, in which a connector is passed through a hole in the material, and load is resisted by shear in the connector and embedment into the surrounding material. Steel dowels were used in a connection between a laminated bamboo member and a steel plate in a central slot in the bamboo, and the behaviour of this connection was compared with a similar connection in timber. The laminated bamboo was made from Moso bamboo (Phyllostachys pubescens) which had been treated by one of two preservative processes, either bleaching or caramelisation. Following testing, substantial qualitative differences between the bamboo and timber specimens were observed: the bamboo failed most often by the formation of a shear plug whereas the timber failed by a single split. The two preservative treatments resulted in different behaviour: the bleached bamboo had a degree of ductility roughly twice that of the caramelised bamboo. Digital image correlation provided full-field strain measurements, which gave further insight into the differences between the materials, particularly between bamboo and timber. Shear strain is dominant in the bamboo, compared with tensile strain perpendicular to grain in the timber. Numerical modelling showed that this difference in the strain field could be explained by the different orthotropic elastic and frictional properties of the two materials.The presented work is supported by a Leverhulme Trust Programme Grant, and EPSRC Grant EP/K023403/1

    Efficacy of rifampicin combination therapy for the treatment of enterococcal infections assessed in vivo using a Galleria mellonella infection model.

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    Enterococci are a leading cause of healthcare-associated infection worldwide and display increasing levels of resistance to many of the commonly used antimicrobials, making treatment of their infections challenging. Combinations of antibiotics are occasionally employed to treat serious infections, allowing for the possibility of synergistic killing. The aim of this study was to evaluate the effects of different antibacterial combinations against enterococcal isolates using an in vitro approach and an in vivo Galleria mellonella infection model. Five Enterococcus faecalis and three Enterococcus faecium strains were screened by paired combinations of rifampicin, tigecycline, linezolid or vancomycin using the chequerboard dilution method. Antibacterial combinations that displayed synergy were selected for in vivo testing using a G. mellonella larvae infection model. Rifampicin was an effective antibacterial enhancer when used in combination with tigecycline or vancomycin, with minimum inhibitory concentrations (MICs) of each individual antibiotic being reduced by between two and four doubling dilutions, generating fractional inhibitory concentration index (FICI) values between 0.31 and 0.5. Synergy observed with the chequerboard screening assays was subsequently observed in vivo using the G. mellonella model, with combination treatment demonstrating superior protection of larvae post-infection in comparison with antibiotic monotherapy. In particular, rifampicin in combination with tigecycline or vancomycin significantly enhanced larvae survival. Addition of rifampicin to anti-enterococcal treatment regimens warrants further investigation and may prove useful in the treatment of enterococcal infections whilst prolonging the clinically useful life of currently active antibiotics

    Super Tall Timber: design research for the next generation of natural structure

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    This research project aspires to make truly tall timber buildings a reality. Through a combination of theoretical design and physical testing this research demonstrates the viability of timber buildings at much greater heights than has previously been possible. By pushing the limits of theoretical designs into the realms of the supertall, sometimes beyond that which is feasible using current materials and construction technologies, this research also sets out the requirements for the next generation of engineered plant-based materials. The research is a collaboration between academics, practicing architects and practicing structural engineers. The approach is research through design, and design through research. Timber towers are designed well beyond exist ing heights, and analysed to understand how they stand up and which areas are most critical for further research. By bringing highly regarded architectural and structural designers together with the research capabilities of a leading university, this project creates a precedent-setting model for interdisciplinary engagement within and between the design and research communities. By coupling exemplary design in timber a university’s research capacity, the project represents a real opportunity for transform ational change in the design of tall timber buildings. Essential details and connections are determined and ‘unknowns’ with respect to material and structural performance are identified. A programme of testing to investigate these unknowns and validate the design approaches is carried out at the university. Outcomes of the test programme and new insights are fed back into the design process. The results show that tall timber towers are feasible, with substantial but surmountable questions outstanding. By providing thought provoking yet credible solutions for the design of tall timber buildings and exceeding current limits, the project can inspire the design community to think beyond the status quo and embrace the possibilities offered by timber construction.The work forms part of a research study conceived and led by Cambridge University with input from PLP Architecture and Smith and Wallwork Engineers. Funding for this research is in part provided by the EPSRC under grant EP/M01679X/1

    Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections.

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    Background: A number of oral diseases, including periodontitis, derive from microbial biofilms and are associated with increased antimicrobial resistance. Despite the widespread use of mouthwashes being used as adjunctive measures to control these biofilms, their prolonged use is not recommended due to various side effects. Therefore, alternative broad-spectrum antimicrobials that minimise these effects are highly sought after. Carbohydrate derived fulvic acid (CHD-FA) is an organic acid which has previously demonstrated to be microbiocidal against Candida albicans biofilms, therefore, the aims of this study were to evaluate the antibacterial activity of CHD-FA against orally derived biofilms and to investigate adjunctive biological effects.<p></p> Methods: Minimum inhibitory concentrations were evaluated for CHD-FA and chlorhexidine (CHX) against a range of oral bacteria using standardised microdilution testing for planktonic and sessile. Scanning electron microscopy was also employed to visualise changes in oral biofilms after antimicrobial treatment. Cytotoxicity of these compounds was assessed against oral epithelial cells, and the effect of CHD-FA on host inflammatory markers was assessed by measuring mRNA and protein expression.<p></p> Results: CHD-FA was highly active against all of the oral bacteria tested, including Porphyromonas gingivalis, with a sessile minimum inhibitory concentration of 0.5%. This concentration was shown to kill multi-species biofilms by approximately 90%, levels comparable to that of chlorhexidine (CHX). In a mammalian cell culture model, pretreatment of epithelial cells with buffered CHD-FA was shown to significantly down-regulate key inflammatory mediators, including interleukin-8 (IL-8), after stimulation with a multi-species biofilm.<p></p> Conclusions: Overall, CHD-FA was shown to possess broad-spectrum antibacterial activity, with a supplementary function of being able to down-regulate inflammation. These properties offer an attractive spectrum of function from a naturally derived compound, which could be used as an alternative topical treatment strategy for oral biofilm diseases. Further studies in vitro and in vivo are required to determine the precise mechanism by which CHD-FA modulates the host immune response.<p></p&gt

    Categorization of species as native or nonnative using DNA sequence signatures without a complete reference library.

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    New genetic diagnostic approaches have greatly aided efforts to document global biodiversity and improve biosecurity. This is especially true for organismal groups in which species diversity has been underestimated historically due to difficulties associated with sampling, the lack of clear morphological characteristics, and/or limited availability of taxonomic expertise. Among these methods, DNA sequence barcoding (also known as "DNA barcoding") and by extension, meta-barcoding for biological communities, has emerged as one of the most frequently utilized methods for DNA-based species identifications. Unfortunately, the use of DNA barcoding is limited by the availability of complete reference libraries (i.e., a collection of DNA sequences from morphologically identified species), and by the fact that the vast majority of species do not have sequences present in reference databases. Such conditions are critical especially in tropical locations that are simultaneously biodiversity rich and suffer from a lack of exploration and DNA characterization by trained taxonomic specialists. To facilitate efforts to document biodiversity in regions lacking complete reference libraries, we developed a novel statistical approach that categorizes unidentified species as being either likely native or likely nonnative based solely on measures of nucleotide diversity. We demonstrate the utility of this approach by categorizing a large sample of specimens of terrestrial insects and spiders (collected as part of the Moorea BioCode project) using a generalized linear mixed model (GLMM). Using a training data set of known endemic (n = 45) and known introduced species (n = 102), we then estimated the likely native/nonnative status for 4,663 specimens representing an estimated 1,288 species (412 identified species), including both those specimens that were either unidentified or whose endemic/introduced status was uncertain. Using this approach, we were able to increase the number of categorized specimens by a factor of 4.4 (from 794 to 3,497), and the number of categorized species by a factor of 4.8 from (147 to 707) at a rate much greater than chance (77.6% accuracy). The study identifies phylogenetic signatures of both native and nonnative species and suggests several practical applications for this approach including monitoring biodiversity and facilitating biosecurity

    Candida albicans biofilm heterogeneity does not influence denture stomatitis but strongly influences denture cleansing capacity

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    Approximately 20  % of the UK population wear some form of denture prosthesis, resulting in denture stomatitis in half of these individuals. Candida albicans is primarily attributed as the causative agent, due to its biofilm -forming ability. Recently, there has been increasing evidence of C. albicans biofilm heterogeneity and the negative impact it can have clinically; however, this phenomenon has yet to be studied in relation to denture isolates. The aims of this study were to evaluate C. albicans biofilm formation of clinical denture isolates in a denture environment and to assess antimicrobial activity of common denture cleansers against these tenacious communities. C. albicans isolated from dentures of healthy and diseased individuals was quantified using real-time PCR and biofilm biomass assessed using crystal violet. Biofilm development on the denture substratum poly(methyl methacrylate), Molloplast B and Ufi-gel was determined. Biofilm formation was assessed using metabolic and biomass stains, following treatment with denture hygiene products. Although C. albicans was detected in greater quantities in diseased individuals, it was not associated with increased biofilm biomass. Denture substrata were shown to influence biofilm biomass, with poly(methyl methacrylate) providing the most suitable environment for C. albicans to reside. Of all denture hygiene products tested, Milton had the most effective antimicrobial activity, reducing biofilm biomass and viability the greatest. Overall, our results highlight the complex nature of denture- related disease, and disease development cannot always be attributed to a sole cause. It is the distinct combination of various factors that ultimately determines the pathogenic outcome

    Development of a High-Throughput Candida albicans Biofilm Chip

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    We have developed a high-density microarray platform consisting of nano-biofilms of Candida albicans. A robotic microarrayer was used to print yeast cells of C. albicans encapsulated in a collagen matrix at a volume as low as 50 nL onto surface-modified microscope slides. Upon incubation, the cells grow into fully formed “nano-biofilms”. The morphological and architectural complexity of these biofilms were evaluated by scanning electron and confocal scanning laser microscopy. The extent of biofilm formation was determined using a microarray scanner from changes in fluorescence intensities due to FUN 1 metabolic processing. This staining technique was also adapted for antifungal susceptibility testing, which demonstrated that, similar to regular biofilms, cells within the on-chip biofilms displayed elevated levels of resistance against antifungal agents (fluconazole and amphotericin B). Thus, results from structural analyses and antifungal susceptibility testing indicated that despite miniaturization, these biofilms display the typical phenotypic properties associated with the biofilm mode of growth. In its final format, the C. albicans biofilm chip (CaBChip) is composed of 768 equivalent and spatially distinct nano-biofilms on a single slide; multiple chips can be printed and processed simultaneously. Compared to current methods for the formation of microbial biofilms, namely the 96-well microtiter plate model, this fungal biofilm chip has advantages in terms of miniaturization and automation, which combine to cut reagent use and analysis time, minimize labor intensive steps, and dramatically reduce assay costs. Such a chip should accelerate the antifungal drug discovery process by enabling rapid, convenient and inexpensive screening of hundreds-to-thousands of compounds simultaneously
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