54 research outputs found

    Leadership after virtue: MacIntyre’s critique of management reconsidered

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    MacIntyre argues that management embodies emotivism, and thus is inherently amoral and manipulative. His claim that management is necessarily Weberian is, at best, outdated, and the notion that management aims to be neutral and value free is incorrect. However, new forms of management, and in particular the increased emphasis on leadership which emerged after MacIntyre’s critique was published, tend to support his central charge. Indeed, charismatic and transformational forms of leadership seem to embody emotivism to a greater degree than do more Weberian, bureaucratic forms of management, so MacIntyre’s central contention about our emotivistic culture seems to be well-founded. Having criticised the details but defended the essence of MacIntyre’s critique of management, this paper sketches a MacIntyrean approach to management and leadership by highlighting the affinities between MacIntyre’s political philosophy and Greenleaf’s concept of servant leadership

    Genome-wide associations for birth weight and correlations with adult disease

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    Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P\textit{P}  < 5 × 108^{-8}). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (R\textit{R}g_{g} = -0.22, P\textit{P}  = 5.5 × 1013^{-13}), T2D (R\textit{R}g_{g} = -0.27, P\textit{P}  = 1.1 × 106^{-6}) and coronary artery disease (R\textit{R}g_{g} = -0.30, P\textit{P}  = 6.5 × 109^{-9}). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P\textit{P} = 1.9 × 104^{-4}). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.For a full list of the funders pelase visit the publisher's website and look at the supplemetary material provided. Some of the funders are: British Heart Foundation, Cancer Research UK, Medical Research Council, National Institutes of Health, Royal Society and Wellcome Trust

    Maintenance of genome stability by Fanconi anemia proteins

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    Oncolytic reovirus enhances rituximab-mediated antibody-dependent cellular cytotoxicity against chronic lymphocytic leukaemia

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    The naturally occurring oncolytic virus (OV), reovirus, replicates in cancer cells causing direct cytotoxicity, and can activate innate and adaptive immune responses to facilitate tumour clearance. Reovirus is safe, well tolerated and currently in clinical testing for the treatment of multiple myeloma, in combination with dexamethasone/carfilzomib. Activation of natural killer (NK) cells has been observed after systemic delivery of reovirus to cancer patients; however, the ability of OV to potentiate NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) is unexplored. This study elucidates the potential of oncolytic reovirus for the treatment of chronic lymphocytic leukaemia (CLL), both as a direct cytotoxic agent and as an immunomodulator. We demonstrate that reovirus: (i) is directly cytotoxic against CLL, which requires replication-competent virus; (ii) phenotypically and functionally activates patient NK cells via a monocyte-derived interferon-α (IFNα)-dependent mechanism; and (iii) enhances ADCC-mediated killing of CLL in combination with anti-CD20 antibodies. Our data provide strong preclinical evidence to support the use of reovirus in combination with anti-CD20 immunotherapy for the treatment of CLL

    Parental beliefs and attitudes towards child caries prevention: assessing consistency and validity in a longitudinal design

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    <p>Abstract</p> <p>Background</p> <p>Exploring the stability of self-reports over time in observational studies may give valuable information for the planning of future interventions. The aims of the present study were: 1) to explore the consistency of parental self-reports of oral health habits, beliefs and attitudes towards child oral health care over a two-year period; 2) to evaluate possible differences in item scores and consistency between parents with different immigrant status; and 3) to assess the construct validity of items measuring parental beliefs and attitudes towards child oral health care.</p> <p>Methods</p> <p>The sample (S1, n = 304) included parents of 3-year-old children in Oslo, Norway; 273 mothers of western origin (WN-group) and 31 of non-western origin (IM-group). They were surveyed in 2002 (child age 3 years) and in 2004 (child age 5 years). Two additional samples of parents were also included; one with 5-year old children in 2002 (S2, n = 382) and one with 3-year-old children in 2004 (S3, n = 427). The questionnaire included items measuring child oral health habits and parental beliefs and attitudes towards child oral health care.</p> <p>Results</p> <p>In 2002, 76.8% of the parents reported that they started to brush their child's teeth before the age of 1 year. Eighty-five percent of them reported the same in 2004; 87.0% of the WN-group and 33.3% of the IM-group (<it>P </it>< 0.001). For 17 of 39 items measuring beliefs and attitudes the responses were more positive for the WN-compared to the IM-group. Parents of caries-free children in 2004 reported significantly more positive beliefs and attitudes towards child oral health care in 2002 compared to parents of children with caries in 2004 (<it>P </it>< 0.05, <it>P </it>< 0.01 and <it>P </it>< 0.001). No differences in mean item scores were found between the three samples S1, S2 and S3.</p> <p>Conclusion</p> <p>The results showed a fair to good consistency of parental self-reports from 2002 to 2004. They also indicate that parents with different cultural backgrounds should be evaluated separately and in a cultural context.</p
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