949 research outputs found

    Pigment analysis by Raman microscopy and portable X-ray fluorescence (pXRF) of thirteenth to fourteenth century illuminations and cuttings from Bologna

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    Non-destructive pigment analysis by Raman microscopy (RM) and portable X-ray fluorescence (pXRF) has been carried out on some Bolognese illuminations and cuttings chosen to represent the beginnings, evolution and height of Bolognese illuminated manuscript production. Dating to the thirteenth and fourteenth centuries and held in a private collection, the study provides evidence for the pigments generally used in this period. The results, which are compared with those obtained for other north Italian artwork, show the developments in usage of artistic materials and technique. Also addressed in this study is an examination of the respective roles of RM and pXRF analysis in this area of technical art history

    An Automated Framework for Structural Test-data Generation

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    Structural testing criteria are mandated in many software development standards and guidelines. The process of generating test data to achieve 100% coverage of a given structural coverage metric is labour-intensive and expensive. This paper presents an approach to automate the generation of such test data. The test-data generation is based on the application of a dynamic optimisation-based search for the required test data. The same approach can be generalised to solve other test-data generation problems. Three such applications are discussed-boundary value analysis, assertion/run-time exception testing, and component re-use testing. A prototype tool-set has been developed to facilitate the automatic generation of test data for these structural testing problems. The results of preliminary experiments using this technique and the prototype tool-set are presented and show the efficiency and effectiveness of this approac

    The regulation of matrix metalloproteinases and their inhibitors

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    The matrix metalloproteinases (MMP) are a family of 23 enzymes in man. These enzymes were originally described as cleaving extracellular matrix (ECM) substrates with a predominant role in ECM homeostasis, but it is now clear that they have much wider functionality. Control over MMP and/or tissue inhibitor of metalloproteinases (TIMP) activity in vivo occurs at different levels and involves factors such as regulation of gene expression, activation of zymogens and inhibition of active enzymes by specific inhibitors. Whilst these enzymes and inhibitors have clear roles in physiological tissue turnover and homeostasis, if control of their expression or activity is lost, they contribute to a number of pathologies including e.g. cancer, arthritis and cardiovascular disease. The expression of many MMPs and TIMPs is regulated at the level of transcription by a variety of growth factors, cytokines and chemokines, though post-transcriptional pathways may contribute to this regulation in specific cases. The contribution of epigenetic modifications has also been uncovered in recent years. The promoter regions of many of these genes have been, at least partly, characterised including the role of identified single nucleotide polymorphisms. This article aims to review current knowledge across these gene families and use a bioinformatic approach to fill the gaps where no functional data are available

    Dickkopf-3 is upregulated in osteoarthritis and has a chondroprotective role

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    Objective Dickkopf-3 (Dkk3) is a non-canonical member of the Dkk family of Wnt antagonists and its upregulation has been reported in microarray analysis of cartilage from mouse models of osteoarthritis (OA). In this study we assessed Dkk3 expression in human OA cartilage to ascertain its potential role in chondrocyte signaling and cartilage maintenance. Methods Dkk3 expression was analysed in human adult OA cartilage and synovial tissues and during chondrogenesis of ATDC5 and human mesenchymal stem cells. The role of Dkk3 in cartilage maintenance was analysed by incubation of bovine and human cartilage explants with interleukin-1 (IL1) and oncostatin-M (OSM). Dkk3 expression was measured in cartilage following murine hip avulsion. Whether Dkk3 influenced Wnt, TGF and activin cell signaling was assessed in primary human chondrocytes and SW1353 chondrosarcoma cells using RT-qPCR and luminescence assays. Results Increased gene and protein levels of Dkk3 were detected in human OA cartilage, synovial tissue and synovial fluid. DKK3 expression was decreased during chondrogenesis of both ATDC5 cells and humans MSCs. Dkk3 inhibited IL1 and OSM-mediated proteoglycan loss from human and bovine cartilage explants and collagen loss from bovine cartilage explans. Cartilage DKK3 expression was decreased following hip avulsion injury. TGF signaling was enhanced by Dkk3 and Wnt3a and activin signaling were inhibited. Conclusions We provide evidence that Dkk3 is upregulated in OA and may have a protective effect on cartilage integrity by preventing proteoglycan loss and helping to restore OA-relevant signaling pathway activity. Targeting Dkk3 may be a novel approach in the treatment of OA

    Why do people want and have the family sizes they do? : influences on family size preferences and behaviour

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    The aims of this study are to investigate influences on the family size preferences and current family size of parents of one to three children, as well as whether they perceive their family as being completed or not. One hundred and two parents participated in this study. The subjects were obtained through word of mouth, contacting childcare centres and advertising. Each subject completed the Family Size Questionnaire and the Childbearing Questionnaire. The Family Size Questionnaire was developed by the researcher and contained questions on the subjects' family size preferences and their own families. The Childbearing Questionnaire (W. Miller, 1994) consists of two sections which measure positive and negative childbearing motivation. The results of this study showed that older subjects want more children than younger subjects, parents with more siblings want more children than those with fewer siblings, and the more children parents currently have, the more children they want. Parents with high positive childbearing motivation want more children, as do those with low negative childbearing motivation. Older subjects had higher current family sizes, as did those who were younger when they had their first child. Parents with high positive childbearing motivation are more likely to be completing their families. Higher education levels and wanting fewer children predicted having completed one's family. Current family size and desired family size may continue to influence each other once childbearing has begun. Traditionally important variables in the area of fertility were not found to influence family size preferences in this sample. This may be related to the possibility that family sizes are decreasing because people are weighing up the advantages and disadvantages more closely on an individual basis. Traditional ideas of what constitutes a family seem to be changing

    Access to Emergency Contraception After Removal of Age Restrictions

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    BACKGROUND: Levonorgestrel emergency contraception (EC) is safe and effective for postcoital pregnancy prevention. Starting in 2013, the US Food and Drug Administration removed age restrictions, enabling EC to be sold over the counter to all consumers. We sought to compare the availability and access for female adolescents with the 2012 study, using the same study design. METHODS: Female mystery callers posing as 17-year-old adolescents in need of EC used standardized scripts to telephone 979 pharmacies in 5 US cities. Using 2015 estimated census data and the federal poverty level, we characterized income levels of pharmacy neighborhoods. RESULTS: Of 979 pharmacies, 827 (83%) indicated that EC was available. This proportion did not vary by pharmacy neighborhood income level, nor was significantly different from the 2012 study (P = .78). When examining access, 8.3% of the pharmacies reported it was impossible to obtain EC under any circumstances, which occurred more often in low-income neighborhoods (10.3% vs 6.3%, adjusted odds ratio 1.5; 95% confidence interval 1.20-1.94). This was not significantly different from 2012 (P = .66). Correct information regarding over-the-counter access was conveyed only 51.6% of the time; accuracy did not differ by pharmacy's neighborhood income (47.9% vs 55.3%, adjusted odds ratio 0.89; 95% confidence interval 0.71-1.11) and was not significantly different from 2012 (P = .37). CONCLUSIONS: A majority of pharmacies have EC available; however, barriers to and disparities in access for adolescents persist and have not changed since the previous study despite regulatory changes that were designed to improve access to EC

    Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease

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    Oxidative stress is proposed as an important factor in osteoarthritis (OA). To investigate the expression of the three superoxide dismutase (SOD) antioxidant enzymes in OA. SOD expression was determined by real-time PCR and immunohistochemistry using human femoral head cartilage. SOD2 expression in Dunkin–Hartley guinea pig knee articular cartilage was determined by immunohistochemistry. The DNA methylation status of the SOD2 promoter was determined using bisulphite sequencing. RNA interference was used to determine the consequence of SOD2 depletion on the levels of reactive oxygen species (ROS) using MitoSOX and collagenases, matrix metalloproteinase 1 (MMP-1) and MMP-13, gene expression. All three SOD were abundantly expressed in human cartilage but were markedly downregulated in end-stage OA cartilage, especially SOD2. In the Dunkin–Hartley guinea pig spontaneous OA model, SOD2 expression was decreased in the medial tibial condyle cartilage before, and after, the development of OA-like lesions. The SOD2 promoter had significant DNA methylation alterations in OA cartilage. Depletion of SOD2 in chondrocytes increased ROS but decreased collagenase expression. This is the first comprehensive expression profile of all SOD genes in cartilage and, importantly, using an animal model, it has been shown that a reduction in SOD2 is associated with the earliest stages of OA. A decrease in SOD2 was found to be associated with an increase in ROS but a reduction of collagenase gene expression, demonstrating the complexities of ROS function

    The Grizzly, February 24, 1984

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    Bio Requirements to be Revised • Best to Perform at Music Forum • Contemporary Plays for proTheatre • Scholarship Competition Opens • Wellness Includes Mind, Body and Spirit • For the Record.. Selling Sex • MacLaine and Winger Come to Terms • Come to the Cabaret • Visit Barnes for Real Art • Aquabears Headed for MACshttps://digitalcommons.ursinus.edu/grizzlynews/1113/thumbnail.jp

    The function of microRNAs in cartilage and osteoarthritis

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    MicroRNAs are small double-stranded RNAs, which negatively regulate gene expression and have been shown to have key roles in both chondrocyte development and cartilage homeostasis with age. Deletion of all microRNAs in chondrocytes leads to skeletal growth defects in mice, whilst deletion of specific mi croRNAs, e.g. miR-140, leads to premature articular cartilage degradation and increased susceptibility to posttraumatic osteoarthritis. Studies comparing microRNA expression in normal human articular cartilage compared to osteoarthritic cartilage show differential expression, but varying sample groups make interpretation difficult. MicroRNAs have been proposed as circulating biomarkers of osteoarthritis, but again, this differs amongst patient cohorts. Many micro- RNAs have been shown to have roles in chondrocyte phenotype via signaling pathways, apoptosis, autophagy and senescence. Modulating microRNAs in the joint has been shown to reduce osteoarthritis in animal models and translating this to man as a novel therapeutic strategy will be key

    Clinical and cost effectiveness of a multi-professional medication reviews in care homes (CAREMED)

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    Objectives With 70% of care home residents experiencing a medication error every day in the UK, better multi‐professional working between medical practitioners, pharmacists and care homes was recommended. The aim of this study was to determine the effectiveness (falls reduction) and cost‐effectiveness, of a multi‐professional medication review (MPMR) service in care homes for older people. Method A total of care homes in the East of England were cluster randomised to ‘usual care’ or two multi‐professional (General practitioner, clinical pharmacist and care homes staff) medication reviews during the 12‐month trial period. Target recruitment was 900 residents with 10% assumed loss to follow‐up. Co‐primary outcome measures were number of falls and potentially inappropriate prescribing assessed by the Screening Tool of Older Persons Prescriptions. Key findings A total of 826 care home residents were recruited with 324 lost to follow‐up for at least one primary outcome measure. The mean number of falls per resident per annum was 3.3 for intervention and 3.0 for control (P = 0.947). Each resident was found to be prescribed 0.69 (intervention) and 0.85 (control) potentially inappropriate medicines after 12 months (P = 0.046). No significant difference identified in emergency hospital admissions or deaths. Estimated unadjusted incremental mean cost per resident was £374.26 higher in the intervention group. Conclusions In line with other medication review based interventions in care homes, two MPMRs improved medication appropriateness but failed to demonstrate improvements in clinical outcomes. From a health system perspective costs where estimated to increase overall and therefore a different model of medicines management is required
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