64 research outputs found

    Teachers\u27 Perceived Effectiveness of Their Evaluation Process at Selected School Districts

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    Starting the journey towards manufacturing excellence : MX Start. Innovation report

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    Manufacturing matters. It matters because of the economic contribution it provides in terms of wealth generation, employment and exports. The manufacturing industry in the United Kingdom can be strengthened. The opportunity for improvement includes closing the productivity gap between other countries, encouraging innovation and developing the skills of the workforce, in order to be globally competitive, drive growth and to help reduce the trade deficit. Critical to exploiting these opportunities, and to the success of the industry, is the adoption of best practice. Existing support for manufacturing improvement can be costly, difficult to access or dependent on input from external experts. This support therefore is not readily accessible to every manufacturing company. There are also a number of quality and performance awards available, however these are predominantly focused on recognising success rather than on how this success can be attained. This research fulfils the gap by providing widely accessible support for manufacturing companies that is focused on helping them to improve. The support provided helps companies to identify and adopt relevant best practices. This research work adapted a product evaluation framework to develop MX Start, a process that supports manufacturing companies to start their improvement journey towards manufacturing excellence. MX Start was developed following a review of the definition of Manufacturing Excellence, a needs assessment of the opportunity, analysis of best practice dissemination strategies, comparative analysis of existing tools and a review of effective self assessment and feedback principles. MX Start provides an easy to use, free of charge, web based system that facilitates manufacturing companies to start their excellence journey. It enables manufacturers to benchmark themselves against best practice in order to gain a greater understanding of what excellence entails, and to enable improvement areas to be identified. This is then supported with a report that helps companies to prioritise the improvement opportunities and provides feedback to then help them make these improvements. The combination of the free of charge, widely accessible, self-directed system that is solely concerned with supporting and encouraging companies to improve, is the basis of the innovation of this work. MX Start has demonstrated impact to the manufacturing industry through a pilot and on-going work with the Manufacturing Advisory Service (MAS). As part of the pilot, over two hundred companies used the process to conduct diagnostic activities to define areas for improvement, and identify where and how they could implement best practices. As a result, MAS in the West Midlands have adopted the tool and supported further developments of this research. This has increased the opportunity for MX Start to help companies progress on their excellence journey and therefore, help support the manufacturing industry to improve. An evaluation of MX Start by companies and manufacturing experts, found that the tool was easy to understand and use, and that it helped companies to identify, and be motivated, to make improvements. The web based system lends itself to further development. In addition to the assessment and report elements of MX Start, the website contains a resource library. The resources contain more information and guidance. The opportunity for the future is to expand this library and build a comprehensive database of support. This would increase the ability of MX Start to support manufacturers to exploit the improvement opportunities to strengthen the competitiveness of the manufacturing industry

    Identifying “hidden” antigens in the liver fluke, Fasciola hepatica

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    Fasciola hepatica is responsible for substantial economic losses and animal welfare issues within the agricultural sector worldwide. The increasing incidence of fasciolosis, coupled with the emergence of flukicide resistance, makes vaccination an attractive alternative control strategy. Hidden antigens extracted from the gut of blood feeding parasites have proven to be excellent vaccine candidates against haematophagous parasites, most notably Haemonchus contortus and Rhipicephalus (Boophilus) microplus. Here, as a first step towards a prototype liverfluke vaccine an attempt to identify hidden gut antigens in F. hepatica was made. Proteomic analysis on extracts of adult F. hepatica was used to identify molecules exclusively found within the membrane-bound fraction including four proteases; cathepsin B2, legumain-2, a putative lysosomal pro-x-carboxypeptidase precursor and a saposin-like protein. Histological sections of adult F. hepatica were screened with a panel of 21 lectins to identify those with an affinity for glycoproteins on the parasite’s gut and to inform subsequent lectin affinity chromatography. Seven lectins showed affinity for the gut region, with peanut (PNA) and jacalin (JAC) lectins binding to glycoproteins on either the gastrodermal cells or gut lamellae, respectively. PNA and JAC were then used to purify glycoproteins from the crude S3 extract by affinity chromatography. The resultant fractions were separated by SDS-PAGE and the protein profiles analysed by mass spectrometry. The enriched lectin-binding fractions shared a number of proteins but one of note that was exclusively identified in the PNA-binding fraction was a cathepsin D-like aspartyl protease, which had not previously been studied in F. hepatica. The proteolytic activities of three somatic extracts of adult F. hepatica were therefore investigated. The ability of the respective fractions to digest haemoglobin, a potential food source, was measured in the presence/absence of class-specific enzyme inhibitors. These analyses confirmed the presence of cathepsin D-like aspartyl protease activity capable of digesting haemoglobin optimally at pH 2 - 2.5. Further characterisation of the cathepsin D-like aspartyl (FhCatD) protease revealed it to be highly conserved within trematodes, to be localized to the gastrodermis of immature (10 day) and adult fluke, and to be more highly expressed, at the RNA level, in the Newly Excysted Juveniles (NEJ) than adult stages. Western blot analysis of native somatic extracts, enriched lectin-binding fractions and recombinant FhCatD using antisera from naturally infected sheep, showed some recognition of the recombinant FhCatD but did not provide clear evidence that the cathepsin D is strongly antigenic during natural infection

    Patterns and trends among physicians-in-training named in civil legal cases: a retrospective analysis of Canadian Medical Protective Association data from 1993 to 2017

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    BACKGROUND: Medico-legal data show opportunities to improve safe medical care; little is published on the experience of physicians-in-training with medical malpractice. The purpose of this study was to examine closed civil legal cases involving physicians-in-training over time and provide novel insights on case and physicians characteristics. METHODS: We conducted a retrospective descriptive study of closed civil legal cases at the Canadian Medical Protective Association (CMPA), a mutual medico-legal defence organization for more than 105 000 physicians, representing an estimated 95% of physicians in Canada. Eligible cases involved at least 1 physician-in-training and were closed between 1993 and 2017 (for time trends) or 2008 and 2017 (for descriptive analyses). We analyzed case rates over time using Poisson regression and the annualized change rate. Descriptive analyses addressed case duration, medico-legal outcome and patient harm. We explored physician specialties and practice characteristics in a subset of cases. RESULTS: Over a 25-year period (1993-2017), 4921 physicians-in-training were named in 2951 closed civil legal cases, and case rates decreased significantly (β = -0.04, 95% confidence interval -0.05 to -0.03, where β was the 1-year difference in log case rates). The annualized change rate was -1.1% per year. Between 2008 and 2017, 1901 (4.1%) of 45 967 physicians-in-training were named in 1107 civil legal cases. Cases with physicians-in-training generally involved more severe patient harm than cases without physicians-in-training. In a subgroup with available information (n = 951), surgical specialties were named most often (n = 531, 55.8%). INTERPRETATION: The rate of civil legal cases involving physicians-in-training has diminished over time, but more recent cases featured severe patient harm and death. Efforts to promote patient safety may enhance medical care and reduce the frequency and severity of malpractice issues for physicians-in-training

    Maternal mental health:a key area for future research among women with congenital heart disease

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    In this viewpoint, we respond to the recently published national priorities for research in congenital heart disease (CHD) among adults, established through the James Lind Alliance Priority Setting Partnership, with specific attention to priority 3 (mental health) and priority 5 (maternal health). Our recent policy impact project explored how maternal mental health is currently addressed in adult congenital heart disease (ACHD) services in the National Health Service, identified gaps and discussed possible ways forward. Our multidisciplinary discussion groups, which included women with lived experience of CHD and pregnancy, cardiology and obstetrics clinicians and medical anthropologists, found that while pregnancy and the postnatal period increase the mental health challenges faced by women with CHD, current services are not yet equipped to address them. Based on this work, we welcome the prioritisation of both mental health and maternal health in ACHD, and suggest that future research should focus on the overlaps between these two priority areas

    777-786

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    Abstract. The cytotoxic effects of strawberry polyphenols were investigated on normal cells and tumour cells derived from the same patient. A human prostate epithelial cell line (P21) and two tumour cell lines (P21 tumour cell line 1 and 2) derived from the same patient, and a normal human breast epithelial cell line (B42) and a tumour line derived from it (B42 clone 16) were used. A polyphenol-rich extract derived from strawberry or anthocyanin or tannin-rich sub-fractions were applied to the cell lines in doses varying from 50 to 1.5 μg/ml. The strawberry extract was cytotoxic with doses of ~5 μg/ml causing a 50% reduction in cell survival in both the normal and the tumour lines. The extracts were also cytotoxic to peripheral blood human lymphocytes stimulated with phytohaemagglutinin but higher levels (>20 μg/ml for 50% reduction in cell survival) were required. After fractionation of the strawberry sample, the cytotoxicity was retained in the tannin-rich fraction and this fraction was considerably more toxic to all cells (normal or tumour cell lines or lymphocytes) than the anthocyanin-rich fraction. Established prostate (LNCaP and PC-3) and breast (MCF-7) tumour cell lines were more resistant to the strawberry extract with concentrations of 50 μg/ml required for 50% reduction in cell survival, which is similar to levels in previous studies on the antiproliferative effects of berry extracts. Although these concentrations are much greater than possible physiological levels, they are comparable to those reported in other studies. From these findings, we conclude that there is little evidence to assume that polyphenols from strawberry have a differential cytotoxic effect on tumour cells relative to comparable normal cells from the same tissue derived from the same patient

    Metformin selectively targets redox control of complex I energy transduction

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    Many guanide-containing drugs are antihyperglycaemic but most exhibit toxicity, to the extent that only the biguanide metformin has enjoyed sustained clinical use. Here, we have isolated unique mitochondrial redox control properties of metformin that are likely to account for this difference. In primary hepatocytes and H4IIE hepatoma cells we found that antihyperglycaemic diguanides DG5-DG10 and the biguanide phenformin were up to 1000-fold more potent than metformin on cell signalling responses, gluconeogenic promoter expression and hepatocyte glucose production. Each drug inhibited cellular oxygen consumption similarly but there were marked differences in other respects. All diguanides and phenformin but not metformin inhibited NADH oxidation in submitochondrial particles, indicative of complex I inhibition, which also corresponded closely with dehydrogenase activity in living cells measured by WST-1. Consistent with these findings, in isolated mitochondria, DG8 but not metformin caused the NADH/NAD+ couple to become more reduced over time and mitochondrial deterioration ensued, suggesting direct inhibition of complex I and mitochondrial toxicity of DG8. In contrast, metformin exerted a selective oxidation of the mitochondrial NADH/NAD+ couple, without triggering mitochondrial deterioration. Together, our results suggest that metformin suppresses energy transduction by selectively inducing a state in complex I where redox and proton transfer domains are no longer efficiently coupled
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