176 research outputs found

    The institutional shaping of management: in the tracks of English individualism

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    Globalisation raises important questions about the shaping of economic action by cultural factors. This article explores the formation of what is seen by some as a prime influence on the formation of British management: individualism. Drawing on a range of historical sources, it argues for a comparative approach. In this case, the primary comparison drawn is between England and Scotland. The contention is that there is a systemic approach to authority in Scotland that can be contrasted to a personal approach in England. An examination of the careers of a number of Scottish pioneers of management suggests the roots of this systemic approach in practices of church governance. Ultimately this systemic approach was to take a secondary role to the personal approach engendered by institutions like the universities of Oxford and Cambridge, but it found more success in the different institutional context of the USA. The complexities of dealing with historical evidence are stressed, as is the value of taking a comparative approach. In this case this indicates a need to take religious practice as seriously as religious belief as a source of transferable practice. The article suggests that management should not be seen as a simple response to economic imperatives, but as shaped by the social and cultural context from which it emerges

    The spectrum and clinical impact of epigenetic modifier mutations in myeloma

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    Epigenetic dysregulation is known to be an important contributor to myeloma pathogenesis but, unlike in other B cell malignancies, the full spectrum of somatic mutations in epigenetic modifiers has not been previously reported. We sought to address this using results from whole-exome sequencing in the context of a large prospective clinical trial of newly diagnosed patients and targeted sequencing in a cohort of previously treated patients for comparison.Whole-exome sequencing analysis of 463 presenting myeloma cases entered in the UK NCRI Myeloma XI study and targeted sequencing analysis of 156 previously treated cases from the University of Arkansas for Medical Sciences. We correlated the presence of mutations with clinical outcome from diagnosis and compared the mutations found at diagnosis with later stages of disease.In diagnostic myeloma patient samples we identify significant mutations in genes encoding the histone 1 linker protein, previously identified in other B-cell malignancies. Our data suggest an adverse prognostic impact from the presence of lesions in genes encoding DNA methylation modifiers and the histone demethylase KDM6A/UTX. The frequency of mutations in epigenetic modifiers appears to increase following treatment most notably in genes encoding histone methyltransferases and DNA methylation modifiers.Numerous mutations identified raise the possibility of targeted treatment strategies for patients either at diagnosis or relapse supporting the use of sequencing-based diagnostics in myeloma to help guide therapy as more epigenetic targeted agents become available

    A general co-expression network-based approach to gene expression analysis: comparison and applications

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    <p>Abstract</p> <p>Background</p> <p>Co-expression network-based approaches have become popular in analyzing microarray data, such as for detecting functional gene modules. However, co-expression networks are often constructed by ad hoc methods, and network-based analyses have not been shown to outperform the conventional cluster analyses, partially due to the lack of an unbiased evaluation metric.</p> <p>Results</p> <p>Here, we develop a general co-expression network-based approach for analyzing both genes and samples in microarray data. Our approach consists of a simple but robust rank-based network construction method, a parameter-free module discovery algorithm and a novel reference network-based metric for module evaluation. We report some interesting topological properties of rank-based co-expression networks that are very different from that of value-based networks in the literature. Using a large set of synthetic and real microarray data, we demonstrate the superior performance of our approach over several popular existing algorithms. Applications of our approach to yeast, Arabidopsis and human cancer microarray data reveal many interesting modules, including a fatal subtype of lymphoma and a gene module regulating yeast telomere integrity, which were missed by the existing methods.</p> <p>Conclusions</p> <p>We demonstrated that our novel approach is very effective in discovering the modular structures in microarray data, both for genes and for samples. As the method is essentially parameter-free, it may be applied to large data sets where the number of clusters is difficult to estimate. The method is also very general and can be applied to other types of data. A MATLAB implementation of our algorithm can be downloaded from <url>http://cs.utsa.edu/~jruan/Software.html</url>.</p

    Network deconvolution as a general method to distinguish direct dependencies in networks

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    Recognizing direct relationships between variables connected in a network is a pervasive problem in biological, social and information sciences as correlation-based networks contain numerous indirect relationships. Here we present a general method for inferring direct effects from an observed correlation matrix containing both direct and indirect effects. We formulate the problem as the inverse of network convolution, and introduce an algorithm that removes the combined effect of all indirect paths of arbitrary length in a closed-form solution by exploiting eigen-decomposition and infinite-series sums. We demonstrate the effectiveness of our approach in several network applications: distinguishing direct targets in gene expression regulatory networks; recognizing directly interacting amino-acid residues for protein structure prediction from sequence alignments; and distinguishing strong collaborations in co-authorship social networks using connectivity information alone. In addition to its theoretical impact as a foundational graph theoretic tool, our results suggest network deconvolution is widely applicable for computing direct dependencies in network science across diverse disciplines.National Institutes of Health (U.S.) (grant R01 HG004037)National Institutes of Health (U.S.) (grant HG005639)Swiss National Science Foundation (Fellowship)National Science Foundation (U.S.) (NSF CAREER Award 0644282

    Predicting Coral Species Richness: The Effect of Input Variables, Diversity and Scale

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    Coral reefs are facing a biodiversity crisis due to increasing human impacts, consequently, one third of reef-building corals have an elevated risk of extinction. Logistic challenges prevent broad-scale species-level monitoring of hard corals; hence it has become critical that effective proxy indicators of species richness are established. This study tests how accurately three potential proxy indicators (generic richness on belt transects, generic richness on point-intercept transects and percent live hard coral cover on point-intercept transects) predict coral species richness at three different locations and two analytical scales. Generic richness (measured on a belt transect) was found to be the most effective predictor variable, with significant positive linear relationships across locations and scales. Percent live hard coral cover consistently performed poorly as anindicator of coral species richness. This study advances the practical framework for optimizing coral reef monitoring programs and empirically demonstrates that generic richness offers an effective way to predict coral species richness with a moderate level of precision. While the accuracy of species richness estimates will decrease in communities dominated byspecies-rich genera (e.g. Acropora), generic richness provides a useful measure of phylogenetic diversity and incorporating this metric into monitoring programs will increase the likelihood that changes in coral species diversity can be detected

    AST: An Automated Sequence-Sampling Method for Improving the Taxonomic Diversity of Gene Phylogenetic Trees

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    A challenge in phylogenetic inference of gene trees is how to properly sample a large pool of homologous sequences to derive a good representative subset of sequences. Such a need arises in various applications, e.g. when (1) accuracy-oriented phylogenetic reconstruction methods may not be able to deal with a large pool of sequences due to their high demand in computing resources; (2) applications analyzing a collection of gene trees may prefer to use trees with fewer operational taxonomic units (OTUs), for instance for the detection of horizontal gene transfer events by identifying phylogenetic conflicts; and (3) the pool of available sequences is biased towards extensively studied species. In the past, the creation of subsamples often relied on manual selection. Here we present an Automated sequence-Sampling method for improving the Taxonomic diversity of gene phylogenetic trees, AST, to obtain representative sequences that maximize the taxonomic diversity of the sampled sequences. To demonstrate the effectiveness of AST, we have tested it to solve four problems, namely, inference of the evolutionary histories of the small ribosomal subunit protein S5 of E. coli, 16 S ribosomal RNAs and glycosyl-transferase gene family 8, and a study of ancient horizontal gene transfers from bacteria to plants. Our results show that the resolution of our computational results is almost as good as that of manual inference by domain experts, hence making the tool generally useful to phylogenetic studies by non-phylogeny specialists. The program is available at http://csbl.bmb.uga.edu/~zhouchan/AST.php

    Threatened reef corals of the world

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    10.1371/journal.pone.0034459PLoS ONE73

    The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

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    AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease
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