47 research outputs found

    Glioma Grading Using Structural Magnetic Resonance Imaging and Molecular Data

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    A glioma grading method using conventional structural magnetic resonance image (MRI) and molecular data from patients is proposed. The noninvasive grading of glioma tumors is obtained using multiple radiomic texture features including dynamic texture analysis, multifractal detrended fluctuation analysis, and multiresolution fractal Brownian motion in structural MRI. The proposed method is evaluated using two multicenter MRI datasets: (1) the brain tumor segmentation (BRATS-2017) challenge for high-grade versus low-grade (LG) and (2) the cancer imaging archive (TCIA) repository for glioblastoma (GBM) versus LG glioma grading. The grading performance using MRI is compared with that of digital pathology (DP) images in the cancer genome atlas (TCGA) data repository. The results show that the mean area under the receiver operating characteristic curve (AUC) is 0.88 for the BRATS dataset. The classification of tumor grades using MRI and DP images in TCIA/TCGA yields mean AUC of 0.90 and 0.93, respectively. This work further proposes and compares tumor grading performance using molecular alterations (IDH1/2 mutations) along with MRI and DP data, following the most recent World Health Organization grading criteria, respectively. The overall grading performance demonstrates the efficacy of the proposed noninvasive glioma grading approach using structural MRI

    Deep Neural Network Analysis of Pathology Images With Integrated Molecular Data for Enhanced Glioma Classification and Grading

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    Gliomas are primary brain tumors that originate from glial cells. Classification and grading of these tumors is critical to prognosis and treatment planning. The current criteria for glioma classification in central nervous system (CNS) was introduced by World Health Organization (WHO) in 2016. This criteria for glioma classification requires the integration of histology with genomics. In 2017, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) was established to provide up-to-date recommendations for CNS tumor classification, which in turn the WHO is expected to adopt in its upcoming edition. In this work, we propose a novel glioma analytical method that, for the first time in the literature, integrates a cellularity feature derived from the digital analysis of brain histopathology images integrated with molecular features following the latest WHO criteria. We first propose a novel over-segmentation strategy for region-of-interest (ROI) selection in large histopathology whole slide images (WSIs). A Deep Neural Network (DNN)-based classification method then fuses molecular features with cellularity features to improve tumor classification performance. We evaluate the proposed method with 549 patient cases from The Cancer Genome Atlas (TCGA) dataset for evaluation. The cross validated classification accuracies are 93.81% for lower-grade glioma (LGG) and high-grade glioma (HGG) using a regular DNN, and 73.95% for LGG II and LGG III using a residual neural network (ResNet) DNN, respectively. Our experiments suggest that the type of deep learning has a significant impact on tumor subtype discrimination between LGG II vs. LGG III. These results outperform state-of-the-art methods in classifying LGG II vs. LGG III and offer competitive performance in distinguishing LGG vs. HGG in the literature. In addition, we also investigate molecular subtype classification using pathology images and cellularity information. Finally, for the first time in literature this work shows promise for cellularity quantification to predict brain tumor grading for LGGs with IDH mutations

    Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.

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    Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery

    A Fatal Case of Herpes Simplex Encephalitis with Two False-Negative Polymerase Chain Reactions

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    An 88-year-old man presented with a 1-month history of altered mental status and seizures. His electrographic and imaging findings were suggestive of herpes simplex encephalitis (HSE), for which he was empirically treated with acyclovir. He underwent two lumbar punctures 3 days apart; both cerebrospinal fluid analyses tested negative for herpes simplex virus (HSV) by polymerase chain reaction (PCR). These negative results and his continued deterioration after 9 days of acyclovir therapy prompted treatment with steroids for possible autoimmune encephalitis. Shortly after the change in management, the patient died from cardiac arrest. At autopsy, his brain showed both gross and microscopic evidence of encephalitis and was positive for HSV by immunohistochemistry. This fatal case of HSE emphasizes the limitations of HSV PCR and the importance of clinical suspicion in the diagnosis and management of this disease

    A review of the catalytic oxidation of carbon-carbon composite aircraft brakes

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    This document is the Accepted Manuscript version, made available under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License CC BY NC-ND 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/. The final, definitive version of this paper is available online at doi: https://doi.org/10.1016/j.carbon.2015.08.100.The use of de-icing chemicals at airport runways has been shown to produce oxides and carbonates of sodium, potassium and calcium which catalyse the oxidation of carbon-carbon composite aircraft brakes leading to an increase of the oxidation rate by an order of magnitude. This review reports on studies that have characterised the catalytic oxidation and discusses the mechanism of the catalytic reaction based on investigations that were carried out with both C-C composites and carbon as a fossil fuel. The alkali metal oxides/carbonates are more active catalysts and in their case, the redox reaction between the monoxides and the peroxides has been identified as the most likely catalysis mechanism. In order to reduce or eliminate the problem of catalysis, doping with boron or phosphorus compounds has been investigated by a number of researchers. The effect of these along with the use of protective coatings is also reviewed.Peer reviewe

    Understanding how immigrant entrepreneurs view business opportunity formation through ethnicity

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    Given that international research is now consistently showing higher rates of entrepreneurial activity from immigrants above native people, research regarding our understanding of how immigrant entrepreneurs view business opportunity formation remains underdeveloped. Based upon a review of the literature, this chapter examines how ethnicity relates to business opportunity formation through constant interactions. It also introduces the Visual Mixed Embeddedness Framework as an empirical lens for understanding the differences in the business opportunity formation process models between immigrant and native entrepreneurs. By explaining how factors and traits from both home and host countries impact upon the immigrant entrepreneurial business activity process, the framework clearly identifies how the concept of ethnicity influences immigrant entrepreneurial opportunity formation activities in different ways. The framework contributes to existing knowledge by offering a novel method for examining the influence on business opportunity formation of ethnicity, the role of home and host countries and variations between immigrant and native entrepreneurs

    Externalizing, internalizing and fostering commitment: the case of born-global firms in emerging economies

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    This paper examines the HR practices of mature born-global firms from twenty-nine emerging economies. Through an examination of large scale survey data the paper questions the extent to which firm size impacts the employment of temporary workers, the employment of skilled workers and the extent of employee training. Findings suggest that as firm size increases the use of temporary workers decreases, the number of skilled workers increases and the number of employees receiving training also increases. The paper highlights how born-global firms are able to shift away from externalized, market-based approaches towards more internalized, commitment-based approaches in order to survive, adapt and grow

    Key mechanisms governing resolution of lung inflammation

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    Innate immunity normally provides excellent defence against invading microorganisms. Acute inflammation is a form of innate immune defence and represents one of the primary responses to injury, infection and irritation, largely mediated by granulocyte effector cells such as neutrophils and eosinophils. Failure to remove an inflammatory stimulus (often resulting in failed resolution of inflammation) can lead to chronic inflammation resulting in tissue injury caused by high numbers of infiltrating activated granulocytes. Successful resolution of inflammation is dependent upon the removal of these cells. Under normal physiological conditions, apoptosis (programmed cell death) precedes phagocytic recognition and clearance of these cells by, for example, macrophages, dendritic and epithelial cells (a process known as efferocytosis). Inflammation contributes to immune defence within the respiratory mucosa (responsible for gas exchange) because lung epithelia are continuously exposed to a multiplicity of airborne pathogens, allergens and foreign particles. Failure to resolve inflammation within the respiratory mucosa is a major contributor of numerous lung diseases. This review will summarise the major mechanisms regulating lung inflammation, including key cellular interplays such as apoptotic cell clearance by alveolar macrophages and macrophage/neutrophil/epithelial cell interactions. The different acute and chronic inflammatory disease states caused by dysregulated/impaired resolution of lung inflammation will be discussed. Furthermore, the resolution of lung inflammation during neutrophil/eosinophil-dominant lung injury or enhanced resolution driven via pharmacological manipulation will also be considered
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