138 results on '"David M. Higgins"'
Search Results
52. Brands, Geographical Origin, and the Global Economy : A History From the Nineteenth Century to the Present
- Author
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David M. Higgins and David M. Higgins
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- Trademarks--Law and legislation--History, Marks of origin--Law and legislation--History, Names, Geographical--Law and legislation--History
- Abstract
Indications of geographic origin for foodstuffs and manufactures have become an important source of brand value since the beginnings of globalization during the late nineteenth century. In this work, David M. Higgins explores the early nineteenth-century business campaigns to secure national and international protection of geographic brands. He shows how these efforts culminated in the introduction of legal protocols which protect such brands, including,'Champagne','Sheffield','Swiss made'watches and'Made in the USA'. Higgins explores the major themes surrounding these indications, tying in the history of global marketing and the relevant laws on intellectual property. He also questions the effectiveness of European Union policy to promote'regional'and'local'foods and why such initiatives brought the EU in conflict with North America, especially the US He extends the study with a reflection on contemporary issues affecting globalization, intellectual property, less developed countries, and supply chains.
- Published
- 2018
53. Patient adaptive maximal resolution magnetic resonance myocardial stress perfusion imaging
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David M. Higgins, Bara Erhayiem, David P Ripley, Tarique A Musa, John P Greenwood, Peter P Swoboda, Sven Plein, Adam K McDiarmid, Akhlaque Uddin, Ananth Kidambi, and Gavin Bainbridge
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Artifact (error) ,medicine.diagnostic_test ,Pulse (signal processing) ,business.industry ,Image quality ,Pulse sequence ,Magnetic resonance imaging ,Temporal resolution ,Medicine ,Radiology, Nuclear Medicine and imaging ,Nuclear medicine ,business ,Image resolution ,Perfusion - Abstract
Purpose To demonstrate the feasibility of an automatic adaptive acquisition sequence. Magnetic resonance perfusion pulse sequences often leave potential acquisition time unused in patients with lower heart-rates (HR) and smaller body size. Materials and Methods A perfusion technique was developed that automatically adapts to HR and field-of-view by maximizing in-plane spatial resolution while maintaining temporal resolution every cardiac cycle. Patients (n = 10) and volunteers (n = 10) were scanned with both a standard resolution and adaptive method. Image quality was scored, signal-to-noise ratio (SNR) calculated, and width of dark-rim artifact (DRA) measured. Results The acquired spatial resolution of the adaptive sequence (1.92 × 1.92 mm2 ± 0.34) was higher than the standard resolution (2.42 × 2.42 mm2) (P
- Published
- 2015
54. Bringing Home the 'Danish' Bacon: Food Chains, National Branding and Danish Supremacy over the British Bacon Market, c. 1900–1938
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David M. Higgins and Mads Mordhorst
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History ,Business, Management and Accounting (miscellaneous) - Published
- 2015
55. Native T1 in Discrimination of Acute and Convalescent Stages in Patients With Clinical Diagnosis of Myocarditis
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David M. Higgins, Gerry Carr-White, Andrew Jabbour, Rocio Hinojar, Tom Jackson, Eduardo Arroyo Ucar, Lucy Foote, Chung Yao Yu, Jane McCrohon, Eike Nagel, Valentina O. Puntmann, and Manuel Mayr
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Cardiac function curve ,medicine.medical_specialty ,Myocarditis ,Viral Myocarditis ,business.industry ,Convalescence ,media_common.quotation_subject ,Disease ,medicine.disease ,Gadobutrol ,Positive predicative value ,Internal medicine ,Cardiology ,Medicine ,Radiology, Nuclear Medicine and imaging ,Stage (cooking) ,Cardiology and Cardiovascular Medicine ,business ,Algorithm ,media_common ,medicine.drug - Abstract
Objectives This study investigated whether T1 mapping by cardiac magnetic resonance (CMR) reflects the clinical evolution of disease in myocarditis and supports its diagnosis independently of the disease stages. Background Acute viral myocarditis is characterized by a range of intracellular changes due to viral replication and extracellular spill of debris within days of viral infection. Convalescence may be characterized by a chronic low-grade inflammation leading to ventricular remodelling, but also a complete resolution of myocardial changes. Methods Patients with clinical diagnosis of viral myocarditis (N = 165) underwent routine clinical CMR protocol (1.5- and 3.0-T) for assessment of cardiac function and structure, and tissue characterization with T2-weighted imaging and late gadolinium enhancement. T1 mapping was obtained in a mid-ventricular short-axis slice before and >20 min after administration of 0.2 mmol/kg of gadobutrol. Results Compared with control subjects (n = 40), T1 indexes were increased in patients with myocarditis. Patients with acute symptoms (n = 61) had higher values of T1 indexes compared with patients in clinical convalescence (n = 67). Native T1 is an independent discriminator between health and disease, as well as a discriminator between acute and convalescent stage of the disease. Native T1- was superior to T2-weighted imaging and late gadolinium enhancement with high diagnostic accuracy and positive and negative predictive values. Using pre-defined cutoff values for normal ranges, we demonstrated that acute myocarditis can be independently identified by native T1 of >5 SD above the mean of normal range, whereas convalescence is best defined by either abnormal native T1 (>2 SD) or presence of late gadolinium enhancement. We prospectively tested a new diagnostic algorithm in an independent dataset of patients with clinical diagnosis of myocarditis and achieved similar diagnostic performance. Conclusions The new diagnostic algorithm using native T1 can reliably discriminate between health and disease and determine the clinical disease stage in patients with a clinical diagnosis of myocarditis.
- Published
- 2015
56. 3.0T, time-resolved, 3D flow-sensitive MR in the thoracic aorta: Impact ofk-tBLAST acceleration using 8- versus 32-channel coil arrays
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Arshad Zaman, David M. Higgins, Gerard Crelier, Manish Motwani, Laura E Dobson, Sven Plein, John P Greenwood, and James Oliver
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Physics ,medicine.diagnostic_test ,Pulse (signal processing) ,Image quality ,business.industry ,Magnetic resonance imaging ,Sense (electronics) ,Stroke volume ,Acceleration ,Electromagnetic coil ,medicine ,Radiology, Nuclear Medicine and imaging ,Streamlines, streaklines, and pathlines ,Nuclear medicine ,business ,Biomedical engineering - Abstract
Purpose: To evaluate the performance of 4D flow MR in the thoracic aorta with 8- and 32-channel coil arrays using k-t BLAST and SENSE acceleration techniques and compare this to a conventional 2D SENSE approach. Materials and Methods: Fifteen healthy subjects and eight patients underwent magnetic resonance imaging (MRI) at 3.0T using: 1) 2D SENSE phase contrast velocity mapping as the reference standard and 2) 4D-flow pulse sequences accelerated with SENSE and k-t BLAST, using both 8- and 32-channel coil arrays. Data processing was performed using GT Flow. Image quality of the magnitude images and pathline visualization were graded and mean scan times, flow, peak velocity, stroke volume, and image quality were compared between techniques. Results: Mean scan times were significantly lower for 4D-flow sequences accelerated with k-t BLAST compared to SENSE (5.5 vs. 25.2 min; P 0.05); the lowest bias being observed with the 4D 32 channel k-t BLAST sequence. There were no significant differences in measured flow, peak velocity, or stroke volume with any of the four investigated 4D acquisition techniques compared to reference technique values (P > 0.05). In patients, there were no significant differences in flow, peak velocity, or stroke volume measurements between 32-channel 4D k-t BLAST and the reference acquisition. Conclusion: 4D flow MR using k-t BLAST and 32 channel coils allows a reduction in total scan time while improving overall image quality compared to a standard 2D SENSE and 4D SENSE acquisitions. The use of 32 channels rather than 8 channels with the 4D k-t BLAST was also preferable in terms of image quality.
- Published
- 2014
57. Dark-blood late gadolinium enhancement without additional magnetization preparation
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René M. Botnar, David M. Higgins, Amedeo Chiribiri, Torben Schneider, Robert J. Holtackers, RS: CARIM - R3.11 - Imaging, Promovendi CD, Beeldvorming, and MUMC+: DA BV Research (9)
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Male ,Pathology ,Contrast Media ,030204 cardiovascular system & hematology ,Late gadolinium enhancement ,030218 nuclear medicine & medical imaging ,Late enhancement ,Coronary artery disease ,0302 clinical medicine ,Medicine ,Myocardial infarction ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,Dark blood ,Middle Aged ,Magnetic Resonance Imaging ,Phase-sensitive inversion-recovery ,MYOCARDIAL VIABILITY ,Cardiology ,cardiovascular system ,SURVIVAL ,CORONARY-ARTERY-DISEASE ,HEART ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,Blood pool ,03 medical and health sciences ,Magnetization ,Cicatrix ,Predictive Value of Tests ,Internal medicine ,Image Interpretation, Computer-Assisted ,Organometallic Compounds ,Journal Article ,Humans ,Radiology, Nuclear Medicine and imaging ,cardiovascular diseases ,Angiology ,Aged ,INVERSION-RECOVERY ,business.industry ,Myocardium ,Reproducibility of Results ,Magnetic resonance imaging ,medicine.disease ,Myocardial scar ,DYSFUNCTION ,HYPERENHANCEMENT ,SCAR ,Delayed enhancement ,Technical Notes ,business - Abstract
Background: This study evaluates a novel dark-blood late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) method, without using additional magnetization preparation, and compares it to conventional bright-blood LGE, for the detection of ischaemic myocardial scar. LGE is able to clearly depict myocardial infarction and macroscopic scarring from viable myocardium. However, due to the bright signal of adjacent left ventricular blood, the apparent volume of scar tissue can be significantly reduced, or even completely obscured. In addition, blood pool signal can mimic scar tissue and lead to false positive observations. Simply nulling the blood magnetization by choosing shorter inversion times, leads to a negative viable myocardium signal that appears equally as bright as scar due to the magnitude image reconstruction. However, by combining blood magnetization nulling with the extended grayscale range of phase-sensitive inversion-recovery (PSIR), a darker blood signal can be achieved whilst a dark myocardium and bright scar signal is preserved.Methods: LGE was performed in nine male patients (63 +/- 11y) using a PSIR pulse sequence, with both conventional viable myocardium nulling and left ventricular blood nulling, in a randomized order. Regions of interest were drawn in the left ventricular blood, viable myocardium, and scar tissue, to assess contrast-to-noise ratios. Maximum scar transmurality, scar size, circumferential scar angle, and a confidence score for scar detection and maximum transmurality were also assessed. Bloch simulations were performed to simulate the magnetization levels of the left ventricular blood, viable myocardium, and scar tissue.Results: Average scar-to-blood contrast was significantly (p Conclusions: Nulling left ventricular blood magnetization for PSIR LGE leads to improved scar-to-blood contrast and increased expert confidence in scar detection and scar transmurality. As no additional magnetization preparation is used, clinical application on current MR systems is readily available without the need for extensive optimizations, software modifications, and/or additional training.
- Published
- 2017
58. A Kinesin-14 Motor Activates Neocentromeres to Promote Meiotic Drive in Maize
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Lisa B. Kanizay, Jonathan I. Gent, Weihong Qiu, Na Wang, Magdy S. Alabady, James A. Birchler, Zhi Gao, Elizabeth G. Lowry, Amy L. Hodges, Jason G. Wallace, Michelle C. Stitzer, Kuo-Fu Tseng, Jeffrey Ross-Ibarra, Alex Harkess, Kyle W. Swentowsky, R. Kelly Dawe, Evelyn N. Hiatt, and David M. Higgins
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0301 basic medicine ,Neocentromere ,Heterochromatin ,Centromere ,Kinesins ,Biology ,Zea mays ,General Biochemistry, Genetics and Molecular Biology ,Chromosomes, Plant ,Evolution, Molecular ,03 medical and health sciences ,Meiosis ,Gene cluster ,RNA, Small Interfering ,Gene ,In Situ Hybridization, Fluorescence ,Phylogeny ,Plant Proteins ,Models, Genetic ,Whole Genome Sequencing ,Cell biology ,030104 developmental biology ,Meiotic drive ,Haplotypes ,Mutagenesis ,DNA methylation ,Kinesin ,RNA Interference - Abstract
Summary Maize abnormal chromosome 10 (Ab10) encodes a classic example of true meiotic drive that converts heterochromatic regions called knobs into motile neocentromeres that are preferentially transmitted to egg cells. Here, we identify a cluster of eight genes on Ab10, called the Kinesin driver ( Kindr ) complex, that are required for both neocentromere motility and preferential transmission. Two meiotic drive mutants that lack neocentromere activity proved to be kindr epimutants with increased DNA methylation across the entire gene cluster. RNAi of Kindr induced a third epimutant and corresponding loss of meiotic drive. Kinesin gliding assays and immunolocalization revealed that KINDR is a functional minus-end-directed kinesin that localizes specifically to knobs containing 180 bp repeats. Sequence comparisons suggest that Kindr diverged from a Kinesin-14A ancestor ∼12 mya and has driven the accumulation of > 500 Mb of knob repeats and affected the segregation of thousands of genes linked to knobs on all 10 chromosomes.
- Published
- 2017
59. Microhemorrhage is an early event in the pulmonary fibrotic disease of PECAM-1 deficient FVB/n mice
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William A. Muller, Alan R. Schenkel, Mercedes Gonzalez-Juarrero, David M. Higgins, Lena C. Young, Steven D. Groshong, Marta Lishnevsky, John Gilchrist, Steven J. Woods, Randall J. Basaraba, and Todd A. Bass
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Pathology ,medicine.medical_specialty ,Bleeding Time ,Pulmonary Fibrosis ,Clinical Biochemistry ,Hemorrhage ,Mice, Inbred Strains ,Vascular permeability ,Hemosiderin ,Article ,Fibrin ,Pathology and Forensic Medicine ,Mice ,Interstitial space ,Macrophages, Alveolar ,Pulmonary fibrosis ,medicine ,Animals ,Platelet ,Myofibroblasts ,Molecular Biology ,medicine.diagnostic_test ,biology ,medicine.disease ,Leukocyte extravasation ,Interleukin-10 ,Platelet Endothelial Cell Adhesion Molecule-1 ,Disease Models, Animal ,Bronchoalveolar lavage ,biology.protein ,Myofibroblast - Abstract
Platelet Endothelial Cell Adhesion Molecule 1 (PECAM-1) deficient mice in the FVB/n strain exhibit fatal chronic pulmonary fibrotic disease. The illness occurs in the absence of a detectable pro-inflammatory event. PECAM-1 is vital to the stability of vascular permeability, leukocyte extravasation, clotting of platelets, and clearance of apoptotic cells. We show here that the spontaneous development of fibrotic disease in PECAM-1 deficient FVB/n mice is characterized by early loss of vascular integrity in pulmonary capillaries, resulting in spontaneous microbleeds. Hemosiderin-positive macrophages were found in interstitial spaces and bronchoalveolar lavage (BAL) fluid in relatively healthy animals. We also observed a gradually increasing presence of hemosiderin-positive macrophages and fibrin deposition in the advanced stages of disease, corresponding to the accumulation of collagen, IL-10 expression, and myofibroblasts expressing alpha smooth muscle actin (SMA). Together with the growing evidence that pulmonary microbleeds and coagulation play an active part in human pulmonary fibrosis, this data further supports our hypothesis that PECAM-1 expression is necessary for vascular barrier function control and regulation of homeostasis specifically, in the pulmonary environment.
- Published
- 2014
60. Robust myocardial T2and T2* mapping at 3T using image-based shimming
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John P Greenwood, Sven Plein, David M. Higgins, Ananth Kidambi, Marc Kouwenhoven, Sebastian Kozerke, Manish Motwani, and Arshad Zaman
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Area at risk ,business.industry ,T2 mapping ,Significant difference ,Medicine ,Radiology, Nuclear Medicine and imaging ,Mapping techniques ,B0 shimming ,business ,Nuclear medicine ,Regional differences ,Image based - Abstract
Purpose Intramyocardial hemorrhage and area at risk are both prognostic markers in acute myocardial infarction (AMI). Myocardial T2 and T2* mapping have been used to detect such tissue changes at 1.5T but these techniques are challenging at 3.0T due to additional susceptibility variation. We studied T2 and T2* myocardial mapping techniques at 3.0T on a system employing B1 shimming and compared two different methods of B0 shimming. Materials and Methods Fifteen volunteers and six AMI patients were scanned on a 3T system. Volume and image-based (IB) B0 shimming techniques were implemented. Single breath-hold, multiecho gradient, and spin echo sequences were employed from which T2* and T2 maps were calculated. Results In volunteers, there was no significant difference in mean values obtained with volume or IB shimming for T2 mapping (39.1 ± 6.0 msec vs. 39.4 ± 6.1 msec; P > 0.05) or for T2* mapping (24.2 ± 6.7 msec vs. 24.1 ± 5.2 msec; P > 0.05). There were no significant regional differences in mean T2 values between septal, anterior, and posterior segments with either shimming technique (all P > 0.05); but there were significant regional differences in mean T2* values using volume shimming (27.8 ± 5.2 msec vs. 28.4 ± 5.8 msec vs. 15.9 ± 8.3 msec; P 0.05). Conclusion At 3.0T, cardiac T2 mapping is robust. Although T2* mapping is prone to more regional heterogeneity this can be reduced by using IB instead of conventional volume B0 shimming. J. Magn. Reson. Imaging 2015;41:1013–1020. © 2014 Wiley Periodicals, Inc.
- Published
- 2014
61. The Maize Divergent spindle-1 (dv1) Gene Encodes a Kinesin-14A Motor Protein Required for Meiotic Spindle Pole Organization
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David M Higgins, Natalie J Nannas, and R Kelly Dawe
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0106 biological sciences ,0301 basic medicine ,Plant Science ,Biology ,lcsh:Plant culture ,kinesin-14A ,maize ,01 natural sciences ,Spindle pole body ,03 medical and health sciences ,meiosis ,lcsh:SB1-1110 ,mutant ,Original Research ,Anaphase ,Genetics ,Kinetochore ,spindle ,Spindle apparatus ,Cell biology ,Spindle checkpoint ,030104 developmental biology ,tubulin ,Meiotic spindle pole ,Spindle organization ,Multipolar spindles ,010606 plant biology & botany - Abstract
The classic maize mutant divergent spindle-1 (dv1) causes failures in meiotic spindle assembly and a decrease in pollen viability. By analyzing two independent dv1 alleles we demonstrate that this phenotype is caused by mutations in a member of the kinesin-14A subfamily, a class of C-terminal, minus-end directed microtubule motors. Further analysis demonstrates that defects in early spindle assembly are rare, but that later stages of spindle organization promoting the formation of finely focused spindle poles are strongly dependent on Dv1. Anaphase is error-prone in dv1 lines but not severely so, and the majority of cells show normal chromosome segregation. Live-cell imaging of wild type and mutant plants carrying CFP-tagged β-tubulin confirm that meiosis in dv1 lines fails primarily at the pole-sharpening phase of spindle assembly. These data indicate that plant kinesin-14A proteins help to enforce bipolarity by focusing spindle poles and that this stage of spindle assembly is not required for transition through the spindle checkpoint but improves the accuracy of chromosome segregation.
- Published
- 2016
- Full Text
- View/download PDF
62. Standardised postprocessing of native T2 in detection and discrimination of myocarditis - comparison with native T1 mapping
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Rocio Hinojar, Eike Nagel, Ciara Cummins, David M. Higgins, Lucy Foote, and Valentina O. Puntmann
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Medicine(all) ,medicine.medical_specialty ,Myocarditis ,Radiological and Ultrasound Technology ,business.industry ,030204 cardiovascular system & hematology ,medicine.disease ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Oral Presentation ,Radiology, Nuclear Medicine and imaging ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,Angiology - Published
- 2016
63. Anaphase asymmetry and dynamic repositioning of the division plane during maize meiosis
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Natalie J. Nannas, R. Kelly Dawe, and David M. Higgins
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0301 basic medicine ,Chromosome movement ,Genetics ,Spindle Apparatus ,Cell Biology ,Biology ,Phragmoplast ,Zea mays ,Chromosomes, Plant ,Cell biology ,Spindle apparatus ,Meiosis ,03 medical and health sciences ,Spindle checkpoint ,Imaging, Three-Dimensional ,030104 developmental biology ,Chromosome Segregation ,Telophase ,Anaphase ,Metaphase ,Multipolar spindles - Abstract
The success of an organism is contingent upon its ability to transmit genetic material through meiotic cell division. In plant meiosis I, the process begins in a large spherical cell without physical cues to guide the process. Yet, two microtubule-based structures, the spindle and phragmoplast, divide the chromosomes and the cell with extraordinary accuracy. Using a live-cell system and fluorescently labeled spindles and chromosomes, we found that the process self- corrects as meiosis proceeds. Metaphase spindles frequently initiate division off-center, and in these cases anaphase progression is asymmetric with the two masses of chromosomes traveling unequal distances on the spindle. The asymmetry is compensatory, such that the chromosomes on the side of the spindle that is farthest from the cell cortex travel a longer distance at a faster rate. The phragmoplast forms at an equidistant point between the telophase nuclei rather than at the original spindle mid-zone. This asymmetry in chromosome movement implies a structural difference between the two halves of a bipolar spindle and could allow meiotic cells to dynamically adapt to errors in metaphase and accurately divide the cell volume.
- Published
- 2016
64. Toward a Cosmopolitan Science Fiction
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David M. Higgins
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Literature ,History ,Literature and Literary Theory ,Conceptualization ,business.industry ,media_common.quotation_subject ,Empire ,Colonialism ,Fully developed ,Politics ,Mode (music) ,Novella ,business ,Interrogation ,media_common - Abstract
Higgins argues that the depth of science fiction's engagement with imperial themes allows the genre to function as a critical literature of empire. As a literary mode engaged with imperial dream-work, science fiction addresses the operations of imperialism more fully than any other mode of cultural production, and it is from this deep understanding of empire (in both its colonial and neocolonial forms) that the genre produces rich cosmopolitan alternatives to imperial discourse and practice. One example of science fiction's successful interrogation of cosmopolitan concerns can be found in Ursula K. Le Guin's Hainish novels. Unlike the work of many other SF authors from the 1960s and 1970s, Le Guin's extrapolations develop throughout her Hainish cycle beyond a straightforward negative critique of imperialism toward a positive and creative conceptualization of cosmopolitan conviviality. The Hainish novels move from a preliminary critique of imperialism and an exploration of cosmopolitan ethics in the early Worlds of Exile and Illusion novellas (1966–67) to a more fully developed imperial critique and a radical imagining of the possible political shapes of instantiated cosmopolitan conviviality in The Left Hand of Darkness (1969). The essay concludes by suggesting that science fiction's celebrations and condemnations of imperial discourse and practice enable the genre as a whole to transcend its own oft-complicit engagements with empire and to generate an imaginative space for the exploration of rich and open-ended cosmopolitan possibilities.
- Published
- 2011
65. Science Fiction and Empire (review)
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David M. Higgins
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Literature ,Postcolonialism ,Binary opposition ,Psychoanalysis ,Visual Arts and Performing Arts ,business.industry ,Communication ,Philosophy ,media_common.quotation_subject ,Empire ,Hybridity ,Orientalism ,Postcolonial literature ,business ,Demon ,The Imaginary ,media_common - Abstract
Patricia Kerslake, Science Fiction and Empire. Liverpool: Liverpool UP, 2007. 217pp. £50 (hbk).David M. HigginsPatricia Kerslake's Science Fiction and Empire opens with the very welcome assertion that sf portrayals of empire offer 'enlightening' insights when 'interrogated by general theories of postcoloniality' (3), and the book's subsequent investigation reads key sf texts through postcolonial lenses. At first, Kerslake avoids arguing that sf itself is a postcolonial literature; instead, she frames sf as a body of fiction that can offer critical perspectives regarding colonialism due to the genre's historical entanglements with imperial discourse. This is an excellent opening move; postcolonial voices clearly offer insightful critiques of empire, and such perspectives can illuminate the imperial (and sometimes anti-imperial) discourses that operate within sf narratives. The book then explores the role of imperial imaginings in the works of Isaac Asimov, Iain M. Banks, Philip K. Dick, Robert A Heinlein, Kurd Lasswitz, Ursula K. Le Guin, Stanislaw Lem, Walter M. Miller, Kim Stanley Robinson, H. G. Wells and John WyndhamFollowing the introduction, the first chapter begins with a summary of 'the postcolonial notion of the Other' as theorised by Edward Said's Orientalism (1978). Said's interrogation of the binary oppositions between self/other and centre/periphery informs much of Kerslake's subsequent discussion of sf; her guiding argument is that sf conducts a variety of thought experiments in which 'self ' encounters 'other', and that these experiments stage a dialectical process in which the 'self ' can ultimately be discovered: 'we are never able to realise what we are in the absence of alterity', she argues, and 'the greater the possible difference between "us" and "them", the greater becomes humanity's potential to develop, and many major works of SF have focused upon this philosophical desire to discover the ultimate condition of humankind' (10). Unfortunately, this argument implies that sf as a whole is committed to the notion of 'humankind' and to an Enlightenment worldview in which human progress unfolds in relation to an 'other' against which the progressive 'self ' can be measured. While this is certainly true of some sf, N. Katherine Hayles and Donna Haraway (among others) have shown that sf may challenge Enlightenment constructions of the 'human', and it is only by avoiding certain sf voices (such as those of Octavia Butler and Samuel Delany) that such an assertion can be made without challenge.This leads to one of my moderate criticisms of the book: Science Fiction and Empire tends to treat both 'postcolonial theory' and 'science fiction' as undifferentiated objects, and Kerslake sometimes defines science fiction against postcolonialism. This opposition reduces both entities into oversimplified straw-men, and in such moments her analysis performs the binary 'othering' that she seeks to expose and unpack in sf itself. Kerslake's analysis is perhaps weakest when she valorises postcolonial theory at the expense of sf; she argues, for example, that 'Postcolonial thought accepts and embraces the concept of the Other, as it enables polyvalency and hybridity, but in SF the Other must forever remain a figure apart: poised somewhere between angel and demon, an existence hovering on the imaginary boundaries of the known' (11). While it is true that some sf holds the other at a distance, much of sf also theorises 'otherness' in complex and interesting ways; Samuel Delany and Brian Aldiss (to name just two examples) were theorising polyvalency alongside poststructuralist and postcolonial critics early in the 1960s, and contemporary television shows such as Battlestar Galactica (US/UK 2003-9), during its best moments, can offer a complex interrogation of imperial self/other constructions. In short, not all (or even most) sf frames the other as an absolute angel or demon. Furthermore, Kerslake's textual readings are sometimes at odds with her theoretical claims in this regard; her own strong analysis of Do Androids Dream of Electric Sheep? …
- Published
- 2010
66. Localized Immunosuppressive Environment in the Foreign Body Response to Implanted Biomaterials
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Eric J. Lee, David W. Grainger, April C. Hohnbaum, Mercedes Gonzalez-Juarrero, Randall J. Basaraba, and David M. Higgins
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Pathology ,medicine.medical_specialty ,Cell type ,Foreign-body giant cell ,Cluster of differentiation ,Chemistry ,Foreign-Body Reaction ,Cell ,CD11c ,Biocompatible Materials ,Immunohistochemistry ,Pathology and Forensic Medicine ,Cell biology ,Mice, Inbred C57BL ,Mice ,medicine.anatomical_structure ,Implants, Experimental ,In vivo ,medicine ,Animals ,Cytokines ,Female ,Tumor necrosis factor alpha ,Regular Articles ,Transforming growth factor - Abstract
The implantation of synthetic biomaterials initiates the foreign body response (FBR), which is characterized by macrophage infiltration, foreign body giant cell formation, and fibrotic encapsulation of the implant. The FBR is orchestrated by a complex network of immune modulators, including diverse cell types, soluble mediators, and unique cell surface interactions. The specific tissue locations, expression patterns, and spatial distribution of these immune modulators around the site of implantation are not clear. This study describes a model for studying the FBR in vivo and specifically evaluates the spatial relationship of immune modulators. We modified a biomaterials implantation in vivo model that allowed for cross-sectional in situ analysis of the FBR. Immunohistochemical techniques were used to determine the localization of soluble mediators, ie, interleukin (IL)-4, IL-13, IL-10, IL-6, transforming growth factor-beta, tumor necrosis factor-alpha, interferon-gamma, and MCP-1; specific cell types, ie, macrophages, neutrophils, fibroblasts, and lymphocytes; and cell surface markers, ie, F4/80, CD11b, CD11c, and Ly-6C, at early, middle, and late stages of the FBR in subcutaneous implant sites. The cytokines IL-4, IL-13, IL-10, and transforming growth factor-beta were localized to implant-adherent cells that included macrophages and foreign body giant cells. A better understanding of the FBR in vivo will allow the development of novel strategies to enhance biomaterial implant design to achieve better performance and safety of biomedical devices at the site of implant.
- Published
- 2009
67. Relative Levels of M-CSF and GM-CSF Influence the Specific Generation of Macrophage Populations during Infection with Mycobacterium tuberculosis
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Mercedes Gonzalez-Juarrero, Eric J. Lee, Adrian G. Rosas-Taraco, Ian M. Orme, Jonathan R. Higgins, Joaquin Sanchez-Campillo, and David M. Higgins
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CD4-Positive T-Lymphocytes ,Tuberculosis ,medicine.medical_treatment ,Immunology ,Cell Count ,C-C chemokine receptor type 7 ,Sensitivity and Specificity ,Mycobacterium tuberculosis ,Interferon-gamma ,Mice ,Transforming Growth Factor beta ,medicine ,Animals ,Immunology and Allergy ,Macrophage ,Cells, Cultured ,MHC class II ,biology ,Macrophage Colony-Stimulating Factor ,Macrophages ,Histocompatibility Antigens Class II ,Granulocyte-Macrophage Colony-Stimulating Factor ,Dendritic Cells ,biology.organism_classification ,Acquired immune system ,medicine.disease ,Phenotype ,Cytokine ,Chronic Disease ,Disease Progression ,biology.protein ,Female ,Lymphocyte Culture Test, Mixed ,Biomarkers - Abstract
Members of the CSF cytokine family play important roles in macrophage recruitment and activation. However, the role of M-CSF in pulmonary infection with Mycobacterium tuberculosis is not clear. In this study, we show the lungs of mice infected with M. tuberculosis displayed a progressive decrease in M-CSF in contrast to increasing levels of GM-CSF. Restoring pulmonary M-CSF levels during infection resulted in a significant decrease in the presence of foamy macrophages and increased expression of CCR7 and MHC class II, specifically on alveolar macrophages. In response to M-CSF, alveolar macrophages also increased their T cell-stimulating capacity and expression of DEC-205. These studies show that the levels of expression of M-CSF and GM-CSF participate in the progression of macrophages into foamy cells and that these cytokines are important factors in the differentiation and regulation of expression of dendritic cell-associated markers on alveolar macrophages. In addition, these studies demonstrate that M-CSF may have a role in the adaptive immune response to infection with M. tuberculosis.
- Published
- 2008
68. XCL1 (lymphotactin) chemokine produced by activated CD8 T cells during the chronic stage of infection withMycobacterium tuberculosisnegatively affects production of IFN-γ by CD4 T cells and participates in granuloma stability
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Marcela Henao-Tamayo, Mercedes Gonzalez Juarrero, Ian M. Orme, Joaquin Sanchez-Campillo, John S. Spencer, Marisa Harton, David M. Higgins, and Diane J. Ordway
- Subjects
CD4-Positive T-Lymphocytes ,T cell ,Immunology ,CD8-Positive T-Lymphocytes ,Biology ,Lymphocyte Activation ,CCL5 ,Interferon-gamma ,Mice ,Interleukin 21 ,medicine ,Animals ,Tuberculosis ,Immunology and Allergy ,Cytotoxic T cell ,IL-2 receptor ,Lung ,Cells, Cultured ,Granuloma ,ZAP70 ,Mycobacterium tuberculosis ,Cell Biology ,Th1 Cells ,Flow Cytometry ,Natural killer T cell ,Chemokines, C ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Chronic Disease ,Cytokines ,Female ,T-Lymphocytes, Cytotoxic ,XCL1 - Abstract
CD8 T cell immune responses are known not to be essential during the initial stages of infection with Mycobacterium tuberculosis (Mtb), but their presence becomes important as the chronic infection ensues. The basis of this is still not clear. In previous studies, we showed that CD8 T cells have a distinctive positioning in the architecture of the granuloma lesion, with further changes throughout the course of the chronic infection. We have also hypothesized that further movement of lymphocytes once they are within the lung lesions could be associated with the levels of expression of the chemokine XCL1 (lymphotactin). XCL1 is produced mainly by activated CD8 T cells, and its chemotactic activity seems primarily controlling movement of CD4 and CD8 T cells. In this study, using a murine low-dose aerosol infection model coupled with antibody depletion of T cell subsets, we investigated the role of CD8 T cells in the control of the bacterial growth and in the pathogenesis of the disease in mice at early, mid, or late stages of the chronic disease state. Additionally, we also describe for the first time that during Mtb infection, activated CD8 T cells in the lungs produce XCL1 and that this chemokine is capable of controlling IFN-γ production by CD4 T cells.
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- 2007
69. The effect of changes to MOLLI scheme on T1 mapping and extra cellular volume calculation in healthy volunteers with 3 tesla cardiovascular magnetic resonance imaging
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Adam K, McDiarmid, David A, Broadbent, David M, Higgins, Peter P, Swoboda, Ananth, Kidambi, David P, Ripley, Bara, Erhayiem, Tarique A, Musa, Laura E, Dobson, John P, Greenwood, and Sven, Plein
- Subjects
Original Article - Abstract
Diffuse myocardial fibrosis may be quantified with magnetic resonance (MR) by calculating extracellular volume (ECV) fraction from native and post-contrast T1 values. The ideal modified look-locker inversion recovery (MOLLI) sequence for deriving T1 values has not been determined. This study aims to establish if systematic differences exist between suggested MOLLI schemes.Twelve phantom gels were studied with inversion recovery spin echo MR at 3.0 tesla to determine reference T1. Gels were then scanned with six MOLLI sequences (3s)3b(3s)5b; 4b(3s)3b(3s)2b; 5b(3s)3b with flip angles of both 35° and 50° at a range of heart rates (HRs). In 10 healthy volunteers MOLLI studies were performed on two separate occasions. Mid ventricular native and post contrast T1 was measured and ECV (%) calculated.In phantoms, the co-efficient of variability at simulated HR [40-100] with a flip angle of 35° ranged from 6.77 to 9.55, and at 50° from 7.71 to 11.10. T1 was under-estimated by all MOLLI acquisitions. Error was greatest with longer T1, and increased as HR increased. The 10 volunteers had normal MR studies. Native T1 time was similar for all acquisitions but highest with the 5b(3s)3b 35° scheme (1,189.1±33.46 ms). Interstudy reproducibility was similar for all MOLLIs.The 5b(3s)3b MOLLI scheme agreed best with reference T1, without statistical difference between the six schemes. The shorter breath-hold time of 5b(3s)3b scheme may be preferable in clinical studies and warrants further investigation.
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- 2015
70. T₁ mapping for assessment of myocardial injury and microvascular obstruction at one week post myocardial infarction
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Donnie, Cameron, Nishat, Siddiqi, Christopher J, Neil, Baljit, Jagpal, Margaret, Bruce, David M, Higgins, Jiabao, He, Satnam, Singh, Thomas W, Redpath, Michael P, Frenneaux, and Dana K, Dawson
- Subjects
Adult ,Aged, 80 and over ,Male ,Time Factors ,Myocardium ,Myocardial Infarction ,Middle Aged ,Coronary Vessels ,Magnetic Resonance Imaging ,Sensitivity and Specificity ,ROC Curve ,Microvessels ,Humans ,Female ,Aged - Abstract
To compare 3T T1 mapping to conventional T2-weighted (T2W) imaging for delineating myocardial oedema one week after ST-elevation myocardial infarction (STEMI), and to explore the confounding effects of microvascular obstruction (MVO) on each technique.T2W spectral attenuated inversion recovery and native T1 mapping were applied in 10 healthy volunteers and 62 STEMI patients, and late gadolinium enhancement was included for infarct localisation at 1 week and at 6 months post-STEMI. Segmental T1 values and T2W signal intensity ratios were calculated; oedema volumes and salvage indices were determined in patients using image thresholding-a receiver operator characteristic (ROC) derived T1 threshold, and a 2SD T2W threshold; and the results were compared between patients with/without MVO (n=35/27).Native T1 mapping delineated oedema with significantly better discriminatory power than T2W-as indicated by ROC analysis (area-under-the-curve, AUC=0.89 versus 0.83, p=0.009; and sensitivity/specificity=83/83% versus 73/73%). The optimal ROC threshold derived for T1 mapping was 1241ms, which gave significantly larger oedema volumes than 2SD T2W (p=0.006); with this threshold, patients with and without MVO showed similar oedema volumes, but patients with MVO had significantly poorer salvage indices (p0.05) than those without. Neither method was significantly affected by MVO, the volume of which was seen to increase exponentially with infarct size.Native T1 mapping at 3T can delineate oedema one week post-STEMI, showing larger oedema volumes and better discriminatory power than T2W imaging, and it is suitable for quantitative thresholding. Both techniques are robust against MVO-related magnetic susceptibility.
- Published
- 2015
71. Native T1 myocardial tissue characterisation in patients with pulmonary hypertension: findings from International T1 Multicentre Study
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David M. Higgins, Anne Keogh, Valentina Otja Puntmann, Shirish Sangle, Eike Nagel, Andrew Jabbour, John G Coghlan, Chung-Yao Yu, Andrew J. Swift, and David D'Cruz
- Subjects
medicine.medical_specialty ,Elevated pulmonary artery pressure ,macromolecular substances ,Gadobutrol ,symbols.namesake ,Internal medicine ,medicine ,Late gadolinium enhancement ,Radiology, Nuclear Medicine and imaging ,cardiovascular diseases ,Angiology ,Medicine(all) ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,medicine.disease ,Pulmonary hypertension ,Bonferroni correction ,cardiovascular system ,Cardiology ,symbols ,Oral Presentation ,Analysis of variance ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Background Pulmonary hypertension is a severe disorder characterized by elevated pulmonary artery pressure leading to right ventricular (RV) failure and premature death. We have recently shown that high signal in septal myocardium by cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) imaging indicates more severe disease. This study investigated whether markers of interstitial septal changes by T1 mapping relate to parameters of biventricular function and structure and makers of disease severity in pulmonary hypertension. Methods Patients with a suspected or established diagnosis of pulmonary hypertension, based on a previous echocardiography or catheterisation, respectively, and control subjects underwent routine clinical CMR protocol (1.5 and 3 Tesla) and T1 mapping prior to and >20 minutes after administration of 0.2 mmol/kg of gadobutrol. T1 values were measured in mid-ventricular slices conservatively within septal myocardium. To transform native T1 values into a binary variable (normal/abnormal), the established cut-offs of >990ms at 1.5T or >1090ms at 3T, respectively, were used. For comparison of two and more than two normally distributed variables, Student’s t-test and one-way analysis of variance (ANOVA, with Bonferroni’s post-hoc test) as appropriate. Associations were explored by single and multivariate linear regressions. Results
- Published
- 2015
72. Split dose versus single bolus gadolinium administration in ecv calculation at 3 tesla cmr
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Bara Erhayiem, Tarique A Musa, David M. Higgins, Laura E Dobson, David P Ripley, Adam K McDiarmid, Sven Plein, John P Greenwood, Ananth Kidambi, Peter P Swoboda, David A. Broadbent, and Pankaj Garg
- Subjects
Medicine(all) ,medicine.medical_specialty ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Stress perfusion ,Gadolinium ,chemistry.chemical_element ,Magnetic resonance imaging ,Clinical Practice ,chemistry ,Single bolus ,Split dose ,Contrast injection ,Poster Presentation ,Medicine ,Radiology, Nuclear Medicine and imaging ,Cardiology and Cardiovascular Medicine ,business ,Nuclear medicine ,Angiology - Abstract
Background Diffuse myocardial fibrosis may be quantified with cardiovascular magnetic resonance (CMR) by calculating extra-cellular volume (ECV) from native and post-contrast T1 values. Previous studies have used either infusion or single bolus contrast administration. In clinical practice however split dose contrast injection is used as part of a stress/rest protocol in stress perfusion studies. The effects of using such an injection regime on ECV calculation is unknown. This study aimed to assess the effects of split dose versus single bolus contrast administration on ECV calculation.
- Published
- 2015
73. Single bolus versus split dose gadolinium administration in extra-cellular volume calculation at 3 Tesla
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David M. Higgins, Bara Erhayiem, Peter P Swoboda, John P Greenwood, Sven Plein, Ananth Kidambi, Adam K McDiarmid, David A. Broadbent, and David P Ripley
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adenosine ,Vasodilator Agents ,Coefficient of variation ,Gadolinium ,Myocardial Ischemia ,Contrast Media ,Magnetic Resonance Imaging, Cine ,chemistry.chemical_element ,Bolus (medicine) ,Organometallic Compounds ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Angiology ,Medicine(all) ,Dose-Response Relationship, Drug ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Research ,Myocardium ,Hypertrophic cardiomyopathy ,Magnetic resonance imaging ,Cardiomyopathy, Hypertrophic ,Middle Aged ,medicine.disease ,Extracellular Matrix ,chemistry ,Split dose ,Female ,Cardiology and Cardiovascular Medicine ,business ,Nuclear medicine ,Perfusion - Abstract
Background Diffuse myocardial fibrosis may be quantified with cardiovascular magnetic resonance (CMR) by calculating extra-cellular volume (ECV) from native and post-contrast T1 values. Accurate ECV calculation is dependent upon the contrast agent having reached equilibrium within tissue compartments. Previous studies have used infusion or single bolus injections of contrast to calculate ECV. In clinical practice however, split dose contrast injection is commonly used as part of stress/rest perfusion studies. In this study we sought to assess the effects of split dose versus single bolus contrast administration on ECV calculation. Methods Ten healthy volunteers and five patients ( 4 ischaemic heart disease, 1 hypertrophic cardiomyopathy) were studied on a 3.0 Tesla (Philips Achieva TX) MR system and underwent two (patients) or three (volunteers) separate CMR studies over a mean of 12 and 30 days respectively. Volunteers underwent one single bolus contrast study (Gadovist 0.15mmol/kg). In two further studies, contrast was given in two boluses (0.075mmol/kg per bolus) as part of a clinical adenosine stress/rest perfusion protocol, boluses were separated by 12 minutes. Patients underwent one bolus and one stress perfusion study only. T1 maps were acquired pre contrast and 15 minutes following the single bolus or second contrast injection. Results ECV agreed between bolus and split dose contrast administration (coefficient of variability 5.04%, bias 0.009, 95% CI −3.754 to 3.772, r2 = 0.973, p = 0.001)). Inter-study agreement with split dose administration was good (coefficient of variability, 5.67%, bias −0.018, 95% CI −4.045 to 4.009, r2 = 0.766, p > 0.001). Conclusion ECV quantification using split dose contrast administration is reproducible and agrees well with previously validated methods in healthy volunteers, as well as abnormal and remote myocardium in patients. This suggests that clinical perfusion CMR studies may incorporate assessment of tissue composition by ECV based on T1 mapping.
- Published
- 2015
74. American Science Fiction after 9/11
- Author
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David M. Higgins
- Subjects
Literature ,business.industry ,media_common.quotation_subject ,Fantasy ,Art ,Science fiction fandom ,Sci-Fi ,business ,media_common - Published
- 2015
75. Improving highly accelerated fat fraction measurements for clinical trials in muscular dystrophy: origin and quantitative effect of R2* changes
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Thomas, Loughran, David M, Higgins, Michelle, McCallum, Anna, Coombs, Volker, Straub, and Kieren G, Hollingsworth
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Adult ,Male ,Clinical Trials as Topic ,Young Adult ,Adipose Tissue ,Humans ,Female ,Middle Aged ,Magnetic Resonance Imaging ,Muscular Dystrophies - Abstract
Purpose To investigate the effect of R2* modeling in conventional and accelerated measurements of skeletal muscle fat fraction in control subjects and patients with muscular dystrophy. Materials and Methods Eight patients with Becker muscular dystrophy and eight matched control subjects were recruited with approval from the Newcastle and North Tyneside 2 Research Ethics Committee and with written consent. Chemical-shift images with six widely spaced echo times (in 3.5-msec increments) were acquired to correlate R2* and muscle fat fraction. The effect of incorporating or neglecting R2* modeling on fat fraction magnitude and variance was evaluated in a typical three-echo protocol (with 0.78-msec increments). Accelerated acquisitions with this protocol with 3.65×, 4.94×, and 6.42× undersampling were reconstructed by using combined compressed sensing and parallel imaging and fat fraction maps produced with R2* modeling. Results Muscle R2* at 3.0 T (33-125 sec(-1)) depended on the morphology of fat replacement, the highest values occurring with the greatest interdigitation of fat. The inclusion of R2* modeling removed bias, which was greatest at low fat fraction, but did not increase variance. The 95% limits of agreement of the accelerated acquisitions were tight and not degraded by R2* modeling (1.65%, 1.95%, and 2.22% for 3.65×, 4.94×, and 6.42× acceleration, respectively). Conclusion Incorporating R2* modeling prevents systematic errors in muscle fat fraction by up to 3.5% without loss of precision and should be incorporated into all muscular dystrophy studies. Fat fraction measurements can be accelerated fivefold by using combined compressed sensing and parallel imaging, modeling for R2* without loss of fidelity.
- Published
- 2015
76. T1 measurement using a short acquisition period for quantitative cardiac applications
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Aleksandra Radjenovic, David M. Higgins, John P. Ridgway, U. Mohan Sivananthan, and Michael A. Smith
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medicine.medical_specialty ,medicine.diagnostic_test ,Cardiac cycle ,business.industry ,Computer science ,media_common.quotation_subject ,Image registration ,Hemodynamics ,Magnetic resonance imaging ,General Medicine ,Iterative reconstruction ,Range (statistics) ,Medical imaging ,medicine ,Curve fitting ,Contrast (vision) ,Computer vision ,Radiology ,Artificial intelligence ,business ,Perfusion ,media_common - Abstract
Myocardial signal intensity curves for myocardial perfusion studies may be made quantitative by the use of T1 measurements made after the first-pass of contrast agent. A short data acquisition method for T1 mapping is presented in which all data for each T1 map are acquired in a short breath hold, and the slice geometry and timing in the cardiac cycle exactly match that of the dynamic first-pass perfusion sequence. This allows accurate image registration of the T1 map with the first-pass series of images. The T1 method is based on varying the preparation-pulse delay time of a saturation recovery sequence, and in this implementation employs an ECG-triggered, single-shot, spoiled gradient echo technique with SENSE reconstruction. The method allows T1 estimates of three slices to be made in fifteen heartbeats. For a range of samples with T1 values equivalent to those found in the myocardium during the first-pass of contrast agent, T1 estimates were accurate to within 6%, and the variation between slices was 2% or less.
- Published
- 2005
77. Effects Of Missing Dynamic Images On Myocardial Perfusion Reserve Index Calculation: Comparison Between An Every Heartbeat And An Alternate Heartbeat Acquisition#
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Holger Thiele, Gerhard Schuler, Marcel Breeuwer, Mohan U. Sivananthan, David M. Higgins, Sven Plein, and John P. Ridgway
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Adult ,Male ,Image Series ,medicine.medical_specialty ,Time Factors ,Heartbeat ,Heart Ventricles ,Rest ,Myocardial Reperfusion ,Coronary Artery Disease ,Coronary artery disease ,Myocardial perfusion imaging ,Heart Rate ,Stress, Physiological ,Coronary Circulation ,Internal medicine ,Image Processing, Computer-Assisted ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Myocardium ,Radiotherapy Planning, Computer-Assisted ,Magnetic resonance imaging ,Middle Aged ,Perfusion reserve ,medicine.disease ,Magnetic Resonance Imaging ,Radiography ,medicine.anatomical_structure ,Ventricle ,cardiovascular system ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Perfusion - Abstract
A commonly used method for analysis of first pass myocardial perfusion imaging is the calculation of a myocardial perfusion reserve index (MPRI) obtained by dividing the upslopes of the time-intensity curves at stress and rest. Perfusion data can be acquired with several different sequences with images acquired at every single, 2nd, or 3rd heartbeat. During data acquisition, some images of the dynamic series can be missed due to extra beats. Twenty-six patients underwent first-pass magnetic resonance perfusion imaging, acquiring images every heartbeat at rest and stress. The maximal upslopes of the myocardium and the left ventricle were calculated for the original image series and for the image series from which dynamics of every 2nd heartbeat were removed. Additionally for each of these situations the upslope calculations were repeated but with the removal of one or two dynamics during the maximal upslope. Images acquired every 2nd heartbeat yielded a lower upslope for the myocardium and the left ventricle, but the resulting MPRI was unchanged. Removing dynamics during the upslope resulted in a change of the MPRI by up to 44% for every heartbeat acquisition and by up to 56% for an alternate sampling. In conclusion, missing data points may affect the calculation of MPRI values and should be taken into account when using such values to define a threshold, which discriminates between normally and abnormally perfused myocardium. Furthermore, it may lead to false positive or negative results in individual cases. This effect is increased if data are acquired only every 2nd heartbeat.
- Published
- 2003
78. Do Metaphors Dream of Literal Sleep? A Science-Fictional Theory of Representation / The Seven Beauties of Science Fiction
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David M. Higgins
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Literature ,Literature and Literary Theory ,business.industry ,media_common.quotation_subject ,Literal (computer programming) ,Sleep (system call) ,Representation (arts) ,Dream ,Psychology ,business ,media_common - Published
- 2012
79. 026 Dimensional flow cardiovascular magnetic resonance: two-centre, 1.5t, phantom and in-vivo validation study
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James R. J. Foley, Pankaj Garg, Sven Plein, Peter P Swoboda, Fgj Tyl, Mohammed S. M. Elbaz, Rahoz Aziz, Graham Fent, Pieter J. Boogaard, David M. Higgins, John P Greenwood, Jos J.M. Westenberg, R.J. van der Geest, and L Coratella
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Pathology ,medicine.medical_specialty ,Validation study ,medicine.diagnostic_test ,Image quality ,business.industry ,Pulsatile flow ,Magnetic resonance imaging ,Imaging phantom ,Respiratory motion correction ,medicine.anatomical_structure ,Flow (mathematics) ,Mitral valve ,medicine ,Cardiology and Cardiovascular Medicine ,Nuclear medicine ,business - Abstract
Background Validation of four-dimensional (4D) flow CMR accelerated acquisition methods is needed to make them more robust for clinical applications.1 Our aim was to compare three widely-used acceleration methods in 4D flow CMR: 4D segmented fast-gradient-echo (4D- turbo-field-echo, 4D-TFE), 4D non-segmented gradient-echo with echo-planar imaging (4D- EPI) and 4D-k-t Broad-use Linear Acquisition Speed-up Technique accelerated TFE (4D-k-t BLAST). Methods CMR was performed in two institutions on identical 1.5T systems. Acceleration methods were compared in static/pulsatile phantoms (Figure 1) and 25 volunteers. In volunteers, the CMR protocol included: cines, 2D phase contrast (PC) at the aortic valve (AV) and mitral valve (MV) and three whole-heart free-breathing (no respiratory motion correction) 4D flow CMR pulse sequences. Field-of-view, slices, phases (30), voxel size and VENC were the same for each subject. In volunteers, net acquisition time for each 4D flow sequence was recorded, as well as a visual grading of image quality on a four-point scale: 0, no artefacts to 3, non-evaluable. Results For the pulsatile phantom experiments, the mean error against the reference flow by time beaker measurements for 4D-TFE was 4.9%±1.3%, for 4D-EPI 7.6%±1.3% and for 4D-k-t BLAST 4.4%±1.9%. In vivo, acquisition time was shortest for 4D-EPI at 7 min59s±2 min30s. 4D- EPI and 4D-k-t BLAST had minimal artefacts, while for 4D-TFE, 40% of AV and MV assessments were non-evaluable because of phase dispersion artefacts. Peak velocity assessment using 4D-EPI demonstrated best correlation to 2D PC (AV: r=0.78, p Conclusion Of the three 4D flow CMR methods tested, 4D-EPI demonstrated the least susceptibility to artefacts, good image quality, modest agreement with the current reference standard for peak intra-cardiac velocities and the highest consistency of intra-cardiac flow quantifications. Competing interests The authors declare that they have no competing interests. Acknowledgement We thank Gavin Bainbridge, Caroline Richmond, Margaret Saysell and Petra Bijsterveld for their invaluable assistance in recruiting and collecting data for this study. Funding Sources This work was supported by the British Heart Foundation [FS/10/62/28409 to S.P.] and Dutch ZonMw [Project Number: 104003001 to J.W]. References . Dyverfeldt P, Bissell M, Barker AJ, Bolger AF, et al. 4D flow cardiovascular magnetic resonance consensus statement. J Cardiovasc Magn Reson2015;17:72.
- Published
- 2017
80. Reference values for healthy human myocardium using a T1 mapping methodology: results from the International T1 Multicenter cardiovascular magnetic resonance study
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David M. Higgins, Eike Nagel, Andrew Jabbour, Darius Dabir, Ananth Kidambi, Lucy Foote, Toby Rogers, Ciara Cummins, Adam K McDiarmid, James Otton, Chung-Yao Yu, Ashwin Kalra, David A. Broadbent, Valentina O. Puntmann, Bernhard Schnackenburg, Rolf Gebker, Sven Plein, and Nicholas Child
- Subjects
Male ,Contrast Media ,Ventricular Function, Left ,Gadobutrol ,Magnetic resonance study ,Medicine(all) ,Aged, 80 and over ,Observer Variation ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,Age Factors ,Middle Aged ,Magnetic Resonance Imaging ,Multicenter study ,MOLLI ,Healthy Volunteers ,Europe ,Native T1 ,Predictive value of tests ,Female ,New South Wales ,Cardiology and Cardiovascular Medicine ,medicine.drug ,Adult ,Accuracy and precision ,medicine.medical_specialty ,Adolescent ,Human myocardium ,Reference values ,Young Adult ,Sex Factors ,Predictive Value of Tests ,Image Interpretation, Computer-Assisted ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Angiology ,Aged ,business.industry ,Research ,Reproducibility of Results ,Magnetic resonance imaging ,T1 mapping ,ECV ,Myocardial Contraction ,Surgery ,Ventricular Function, Right ,Nuclear medicine ,business - Abstract
Background T1 mapping is a robust and highly reproducible application to quantify myocardial relaxation of longitudinal magnetisation. Available T1 mapping methods are presently site and vendor specific, with variable accuracy and precision of T1 values between the systems and sequences. We assessed the transferability of a T1 mapping method and determined the reference values of healthy human myocardium in a multicenter setting. Methods Healthy subjects (n = 102; mean age 41 years (range 17–83), male, n = 53 (52%)), with no previous medical history, and normotensive low risk subjects (n=113) referred for clinical cardiovascular magnetic resonance (CMR) were examined. Further inclusion criteria for all were absence of regular medication and subsequently normal findings of routine CMR. All subjects underwent T1 mapping using a uniform imaging set-up (modified Look- Locker inversion recovery, MOLLI, using scheme 3(3)3(3)5)) on 1.5 Tesla (T) and 3 T Philips scanners. Native T1-maps were acquired in a single midventricular short axis slice and repeated 20 minutes following gadobutrol. Reference values were obtained for native T1 and gadolinium-based partition coefficients, λ and extracellular volume fraction (ECV) in a core lab using standardized postprocessing. Results In healthy controls, mean native T1 values were 950 ± 21 msec at 1.5 T and 1052 ± 23 at 3 T. λ and ECV values were 0.44 ± 0.06 and 0.25 ± 0.04 at 1.5 T, and 0.44 ± 0.07 and 0.26 ± 0.04 at 3 T, respectively. There were no significant differences between healthy controls and low risk subjects in routine CMR parameters and T1 values. The entire cohort showed no correlation between age, gender and native T1. Cross-center comparisons of mean values showed no significant difference for any of the T1 indices at any field strength. There were considerable regional differences in segmental T1 values. λ and ECV were found to be dose dependent. There was excellent inter- and intraobserver reproducibility for measurement of native septal T1. Conclusion We show transferability for a unifying T1 mapping methodology in a multicenter setting. We provide reference ranges for T1 values in healthy human myocardium, which can be applied across participating sites. Electronic supplementary material The online version of this article (doi:10.1186/s12968-014-0069-x) contains supplementary material, which is available to authorized users.
- Published
- 2014
81. Patient adaptive maximal resolution magnetic resonance myocardial stress perfusion imaging
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David P, Ripley, Adam K, McDiarmid, Ananth, Kidambi, Akhlaque, Uddin, Peter P, Swoboda, Tarique A, Musa, Bara, Erhayiem, Gavin J, Bainbridge, John P, Greenwood, Sven, Plein, and David M, Higgins
- Subjects
Adult ,Cardiac-Gated Imaging Techniques ,Myocardial Perfusion Imaging ,Reproducibility of Results ,Coronary Artery Disease ,Middle Aged ,Image Enhancement ,Magnetic Resonance Imaging ,Sensitivity and Specificity ,Young Adult ,Image Interpretation, Computer-Assisted ,Exercise Test ,Body Size ,Feasibility Studies ,Humans ,Precision Medicine ,Aged - Abstract
To demonstrate the feasibility of an automatic adaptive acquisition sequence. Magnetic resonance perfusion pulse sequences often leave potential acquisition time unused in patients with lower heart-rates (HR) and smaller body size.A perfusion technique was developed that automatically adapts to HR and field-of-view by maximizing in-plane spatial resolution while maintaining temporal resolution every cardiac cycle. Patients (n = 10) and volunteers (n = 10) were scanned with both a standard resolution and adaptive method. Image quality was scored, signal-to-noise ratio (SNR) calculated, and width of dark-rim artifact (DRA) measured.The acquired spatial resolution of the adaptive sequence (1.92 × 1.92 mm(2) ± 0.34) was higher than the standard resolution (2.42 × 2.42 mm(2) ) (P 0.0001). Mean DRA width was reduced using the adaptive pulse sequence (1.94 ± 0.60 mm vs. 2.82 ± 0.65 mm, P 0.0001). The signal-to-noise ratio (SNR) was higher with the standard pulse sequence (6.7 ± 2.2 vs. 3.8 ± 1.8, P 0.0001). There was no difference in image quality score between sequences in either volunteers (1.1 ± 0.31 vs. 1.0 ± 0.0, P = 0.34) or patients (1.3 ± 0.48 vs. 1.3 ± 0.48, P = 1.0).Optimizing the use of available imaging time during first-pass perfusion with a magnetic resonance imaging pulse sequence that adapts image acquisition duration to HR and patient size is feasible. Acquired in-plane spatial resolution is improved, the DRA is reduced, and while SNR is reduced with the adaptive sequence consistent with the lower voxel size used, image quality is maintained.
- Published
- 2014
82. Aortic stiffness and interstitial myocardial fibrosis by native T1 are independently associated with left ventricular remodeling in patients with dilated cardiomyopathy
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Valentina O. Puntmann, Sven Plein, David M. Higgins, Ciara Cummins, Alexandra Macmillan, Ning Binti Ngah, Eike Nagel, Gerry Carr-White, Phil Chowienczyk, Nicholas Gaddum, Rocio Hinojar Baydes, Darius Dabir, Eduardo Arroyo Ucar, and Yen-Shu Kuo
- Subjects
Adult ,Cardiomyopathy, Dilated ,Male ,medicine.medical_specialty ,Endomyocardial fibrosis ,Cardiomyopathy ,Blood Pressure ,Pulse Wave Analysis ,Ventricular Dysfunction, Left ,Vascular Stiffness ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Ventricular remodeling ,Pulse wave velocity ,Aged ,Ventricular Remodeling ,business.industry ,Myocardium ,Dilated cardiomyopathy ,Middle Aged ,medicine.disease ,Fibrosis ,Logistic Models ,Heart failure ,Multivariate Analysis ,Arterial stiffness ,Cardiology ,Aortic stiffness ,Female ,business - Abstract
Increased aortic stiffness is related to increased ventricular stiffness and remodeling. Myocardial fibrosis is the pathophysiological hallmark of failing heart. We investigated the relationship between noninvasive imaging markers of myocardial fibrosis, native T1, and late gadolinium enhancement, respectively, and aortic stiffness in ventricular remodeling. Consecutive patients with known dilated cardiomyopathy (n=173) underwent assessment of cardiac volumes and function, T1 mapping, scar imaging, and pulse wave velocity, a measure of aortic stiffness. Asymptomatic healthy volunteers served as controls (n=47). Controls and patients showed an increase in pulse wave velocity with age, which was accelerated in the presence of cardiovascular disease. On the contrary, native T1 increased with age in patients, but not in controls. Pulse wave velocity was associated with native T1 in the presence of disease, but not in health. Native T1 showed a strong relationship with markers of structural and functional left ventricular remodeling and diastolic impairment. Ischemic and nonischemic pathophysiology of ventricular remodeling showed a similar slope of relationship between pulse wave velocity and native T1. However, in nonischemic patients, increase in pulse wave velocity was associated with greater increase in native T1. Aortic stiffness is related to age, and this process is accelerated in the presence of disease. On the contrary, increase in interstitial myocardial fibrosis is associated with age in the presence of disease. Patients with ischemic and nonischemic dilated cardiomyopathy have a similar relationship between native T1 and pulse wave velocity, which is stronger in the latter group.
- Published
- 2014
83. Susceptibility-weighted cardiovascular magnetic resonance in comparison to T2 and T2 star imaging for detection of intramyocardial hemorrhage following acute myocardial infarction at 3 Tesla
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John D Biglands, Tarique A Musa, Ananth Kidambi, David M. Higgins, John P Greenwood, Arshad Zaman, David A. Broadbent, Peter P Swoboda, Sven Plein, Bara Erhayiem, David P Ripley, and Adam K McDiarmid
- Subjects
Adult ,Gadolinium DTPA ,Male ,medicine.medical_specialty ,Time Factors ,Image quality ,medicine.medical_treatment ,Myocardial Infarction ,Contrast Media ,Magnetic Resonance Imaging, Cine ,Diagnostic accuracy ,Hemorrhage ,Myocardial Reperfusion Injury ,Percutaneous Coronary Intervention ,Magnetic resonance imaging ,Predictive Value of Tests ,Image Interpretation, Computer-Assisted ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Myocardial infarction ,Angiology ,Aged ,Medicine(all) ,Observer Variation ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Myocardium ,Research ,Percutaneous coronary intervention ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Treatment Outcome ,Susceptibility ,Predictive value of tests ,Female ,Cardiovascular magnetic resonance ,Radiology ,Myocardial infarction diagnosis ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Intramyocardial hemorrhage (IMH) identified by cardiovascular magnetic resonance (CMR) is an established prognostic marker following acute myocardial infarction (AMI). Detection of IMH by T2-weighted or T2 star CMR can be limited by long breath hold times and sensitivity to artefacts, especially at 3T. We compared the image quality and diagnostic ability of susceptibility-weighted magnetic resonance imaging (SW MRI) with T2-weighted and T2 star CMR to detect IMH at 3T. Methods Forty-nine patients (42 males; mean age 58 years, range 35–76) underwent 3T cardiovascular magnetic resonance (CMR) 2 days following re-perfused AMI. T2-weighted, T2 star and SW MRI images were obtained. Signal and contrast measurements were compared between the three methods and diagnostic accuracy of SW MRI was assessed against T2w images by 2 independent, blinded observers. Image quality was rated on a 4-point scale from 1 (unusable) to 4 (excellent). Results Of 49 patients, IMH was detected in 20 (41%) by SW MRI, 21 (43%) by T2-weighted and 17 (34%) by T2 star imaging (p = ns). Compared to T2-weighted imaging, SW MRI had sensitivity of 93% and specificity of 86%. SW MRI had similar inter-observer reliability to T2-weighted imaging (κ = 0.90 and κ = 0.88 respectively); both had higher reliability than T2 star (κ = 0.53). Breath hold times were shorter for SW MRI (4 seconds vs. 16 seconds) with improved image quality rating (3.8 ± 0.4, 3.3 ± 1.0, 2.8 ± 1.1 respectively; p
- Published
- 2014
84. Native T1 in discrimination of acute and convalescent stages in patients with clinical diagnosis of myocarditis: a proposed diagnostic algorithm using CMR
- Author
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Rocio, Hinojar, Lucy, Foote, Eduardo, Arroyo Ucar, Thomas, Jackson, Andrew, Jabbour, Chung-Yao, Yu, Jane, McCrohon, David M, Higgins, Gerry, Carr-White, Manuel, Mayr, Eike, Nagel, and Valentina O, Puntmann
- Subjects
Myocarditis ,Virus Diseases ,Myocardium ,Humans ,Prospective Studies ,Magnetic Resonance Imaging ,Algorithms - Abstract
This study investigated whether T1 mapping by cardiac magnetic resonance (CMR) reflects the clinical evolution of disease in myocarditis and supports its diagnosis independently of the disease stages.Acute viral myocarditis is characterized by a range of intracellular changes due to viral replication and extracellular spill of debris within days of viral infection. Convalescence may be characterized by a chronic low-grade inflammation leading to ventricular remodelling, but also a complete resolution of myocardial changes.Patients with clinical diagnosis of viral myocarditis (N = 165) underwent routine clinical CMR protocol (1.5- and 3.0-T) for assessment of cardiac function and structure, and tissue characterization with T2-weighted imaging and late gadolinium enhancement. T1 mapping was obtained in a mid-ventricular short-axis slice before and20 min after administration of 0.2 mmol/kg of gadobutrol.Compared with control subjects (n = 40), T1 indexes were increased in patients with myocarditis. Patients with acute symptoms (n = 61) had higher values of T1 indexes compared with patients in clinical convalescence (n = 67). Native T1 is an independent discriminator between health and disease, as well as a discriminator between acute and convalescent stage of the disease. Native T1- was superior to T2-weighted imaging and late gadolinium enhancement with high diagnostic accuracy and positive and negative predictive values. Using pre-defined cutoff values for normal ranges, we demonstrated that acute myocarditis can be independently identified by native T1 of5 SD above the mean of normal range, whereas convalescence is best defined by either abnormal native T1 (2 SD) or presence of late gadolinium enhancement. We prospectively tested a new diagnostic algorithm in an independent dataset of patients with clinical diagnosis of myocarditis and achieved similar diagnostic performance.The new diagnostic algorithm using native T1 can reliably discriminate between health and disease and determine the clinical disease stage in patients with a clinical diagnosis of myocarditis.
- Published
- 2014
85. Review of T1 Mapping Methods: Comparative Effectiveness Including Reproducibility Issues
- Author
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David M. Higgins and James C. Moon
- Subjects
Reproducibility ,medicine.medical_specialty ,Histology ,medicine.diagnostic_test ,business.industry ,Fat content ,Magnetic resonance imaging ,Cell Biology ,Applied Microbiology and Biotechnology ,Biomarker (cell) ,T1 measurement ,Diffuse fibrosis ,Internal medicine ,Iron content ,medicine ,Cardiology ,Myocardial disease ,business - Abstract
Myocardial T1 mapping by cardiovascular magnetic resonance (CMR) is a key emerging biomarker for quantification of myocardial disease. Native myocardial T1 changes with fat content, iron content, and increased myocardial extracellular water (oedema, focal or diffuse fibrosis, amyloidosis). With the addition of a contrast agent, the extracellular volume (ECV) can be estimated, a robust measure of interstitial space expansion. A number of cardiac T1 mapping methods are currently being used; a selection of these is described. Factors affecting the accuracy, precision and reproducibility of these methods are discussed, including the impact these will have in certain clinical circumstances. Challenges for delivery of T1 mapping to healthcare are examined, including validation, quality control, and protocol transfer between MR systems. As the technique becomes established, key methodology considerations for early adopters are highlighted.
- Published
- 2014
86. 3.0T, time-resolved, 3D flow-sensitive MR in the thoracic aorta: Impact of k-t BLAST acceleration using 8- versus 32-channel coil arrays
- Author
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Arshad, Zaman, Manish, Motwani, James J, Oliver, Gerard, Crelier, Laura E, Dobson, David M, Higgins, Sven, Plein, and John P, Greenwood
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Adult ,Male ,Transducers ,Reproducibility of Results ,Aorta, Thoracic ,Signal Processing, Computer-Assisted ,Equipment Design ,Middle Aged ,Image Enhancement ,Sensitivity and Specificity ,Equipment Failure Analysis ,Young Adult ,Imaging, Three-Dimensional ,Reference Values ,Humans ,Female ,Blood Flow Velocity ,Magnetic Resonance Angiography - Abstract
To evaluate the performance of 4D flow MR in the thoracic aorta with 8- and 32-channel coil arrays using k-t BLAST and SENSE acceleration techniques and compare this to a conventional 2D SENSE approach.Fifteen healthy subjects and eight patients underwent magnetic resonance imaging (MRI) at 3.0T using: 1) 2D SENSE phase contrast velocity mapping as the reference standard and 2) 4D-flow pulse sequences accelerated with SENSE and k-t BLAST, using both 8- and 32-channel coil arrays. Data processing was performed using GT Flow. Image quality of the magnitude images and pathline visualization were graded and mean scan times, flow, peak velocity, stroke volume, and image quality were compared between techniques.Mean scan times were significantly lower for 4D-flow sequences accelerated with k-t BLAST compared to SENSE (5.5 vs. 25.2 min; P0.01). 4D k-t BLAST acquisition had greater magnitude and pathline image quality than 4D SENSE acquisition for both 32-channel and 8-channel data (P0.001); both 4D SENSE and 4D k-t BLAST acquisitions had significantly greater image quality when 32 channels were utilized compared to 8 (P0.05). On Bland-Altman analysis, all 4D flow pulse sequences showed significant agreement with the 2D SENSE reference for peak velocity measurement (P0.05); the lowest bias being observed with the 4D 32 channel k-t BLAST sequence. There were no significant differences in measured flow, peak velocity, or stroke volume with any of the four investigated 4D acquisition techniques compared to reference technique values (P0.05). In patients, there were no significant differences in flow, peak velocity, or stroke volume measurements between 32-channel 4D k-t BLAST and the reference acquisition.4D flow MR using k-t BLAST and 32 channel coils allows a reduction in total scan time while improving overall image quality compared to a standard 2D SENSE and 4D SENSE acquisitions. The use of 32 channels rather than 8 channels with the 4D k-t BLAST was also preferable in terms of image quality.
- Published
- 2013
87. Zoster related multiple cranial nerve palsies: an unusual complication following percutaneous balloon compression for trigeminal neuralgia
- Author
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David M. Higgins, Andrew C Kam, Julia Maclean, and Noel G Dan
- Subjects
Trigeminal nerve ,medicine.medical_specialty ,Accessory nerve ,business.industry ,viruses ,Cranial nerves ,virus diseases ,General Medicine ,medicine.disease ,Surgery ,Trigeminal ganglion ,Neurology ,Trigeminal neuralgia ,Physiology (medical) ,medicine ,Paralysis ,Neuralgia ,Cranial nerve disease ,Neurology (clinical) ,medicine.symptom ,business - Abstract
A patient demonstrating multiple cranial nerve palsies involving the IXth, Xth, XIth and XIIth cranial nerves following percutaneous balloon compression of the trigeminal ganglion for post-herpetic trigeminal neuralgia is presented. This collection of lower cranial nerve palsies, including the accessory nerve, has not been previously described as a complication of this procedure. This unusual group of cranial nerve palsies resulted from reactivation of the varicella-zoster virus (VZV) secondary to the procedure.
- Published
- 1999
88. Picturing the Death of Osama bin Laden: Political Iconoclasm in the Digital Age
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Marion G. Müller and David M. Higgins
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Politics ,History ,Iconoclasm ,Religious studies ,Bin - Published
- 2013
89. Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis
- Author
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Kelly Queensland, Zung Vu Tran, Joel E. Wilson, David M. Higgins, Lindsay Weitzel, Haley G. Hutting, Christine Baird, Paul E. Wischmeyer, Ludmila Khailova, and Natalie J. Serkova
- Subjects
Male ,medicine.medical_treatment ,Adrenergic beta-Antagonists ,Hemodynamics ,Propranolol ,030204 cardiovascular system & hematology ,Pharmacology ,Critical Care and Intensive Care Medicine ,Drug Administration Schedule ,Sepsis ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Metabolic Diseases ,Heat shock protein ,medicine ,Animals ,Lung ,Septic shock ,business.industry ,Research ,030208 emergency & critical care medicine ,medicine.disease ,3. Good health ,Rats ,Survival Rate ,Cytokine ,medicine.anatomical_structure ,Treatment Outcome ,Anesthesia ,Enzyme Induction ,Heme Oxygenase (Decyclizing) ,Tumor necrosis factor alpha ,business ,medicine.drug - Abstract
Introduction Pharmacological agents that block beta-adrenergic receptors have been associated with improved outcome in burn injury. It has been hypothesized that injuries leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade; however, outcome data in experimental models have been contradictory. Thus, we investigated the effect of beta-blockade with propranolol on survival, hemodynamics, lung heat shock protein (HSP) expression, metabolism and inflammatory markers in a rat cecal ligation and puncture (CLP) model of sepsis. Methods Sprague-Dawley rats receiving either repeated doses (30 minutes pre-CLP and every 8 hours for 24 hours postoperatively) of propranolol or control (normal saline), underwent CLP and were monitored for survival. Additionally, lung and blood samples were collected at 6 and 24 hours for analysis. Animals also underwent monitoring to evaluate global hemodynamics. Results Seven days following CLP, propranolol improved survival versus control (P < 0.01). Heart rates in the propranolol-treated rats were approximately 23% lower than control rats (P < 0.05) over the first 24 hours, but the mean arterial blood pressure was not different between groups. Metabolic analysis of lung tissue demonstrated an increase in lung ATP/ADP ratio and NAD+ content and a decreased ratio of polyunsaturated fatty acids to monounsaturated fatty acids (PUFA/MUFA). Cytokine analysis of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) demonstrated decreased expression of TNF-alpha in both lung and plasma at 24 hours post CLP induced sepsis. Finally, propranolol led to a significant increase in lung hemeoxygenase-1 expression, a key cellular protective heat shock protein (HSP) in the lung. Other lung HSP expression was unchanged. Conclusions These results suggest that propranolol treatment may decrease mortality during sepsis potentially via a combination of improving metabolism, suppressing aspects of the inflammatory response and enhancing tissue protection.
- Published
- 2012
90. D Impact of High-Flow Oxygen on Perfusion, Microvascular and Capilliary Function in Normal Volunteers and Patients with Coronary Artery Disease: A Cardiovascular Magnetic Resonance and Invasive Coronary Physiology Study
- Author
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Foley Jrj, John P Greenwood, Sven Plein, David Corcoran, Ripley Dp, David M. Higgins, David P Ripley, Colin Berry, and David A. Broadbent
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,chemistry.chemical_element ,Perfusion scanning ,Magnetic resonance imaging ,Fractional flow reserve ,Blood flow ,medicine.disease ,Oxygen ,Surgery ,Coronary artery disease ,chemistry ,Blood Volume Fraction ,Internal medicine ,medicine ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Perfusion - Abstract
Introduction Supplemental oxygen has long been used as a therapeutic agent in the management of ischaemic chest pain, but without a sound scientific basis. We proposed to investigate the effect of high-flow oxygen on coronary physiology, invasively and non-invasively, in those with severe coronary artery disease (CAD). Methods 30 volunteers and 30 patients with severe CAD were allocated to receive high-flow air and oxygen in a random blinded order. They underwent cardiovascular magnetic resonance (CMR) T2* blood-oxygen level dependent (BOLD) and dynamic contrast-enhanced perfusion imaging. Myocardial blood flow (MBF), perfusion reserve (MPR), first-pass extraction fraction (E), blood volume fraction (v b ) and capillary permeability-surface area product (PS) were quantified using bookend T 1 based non-linearity correction and distributed parameter model constrained deconvolution. Invasive coronary physiology measurements were performed in severe CAD patients (Fractional Flow Reserve Results In volunteers the change in BOLD Air-T2* was 6.1 ± 7.5 ms vs. O 2 -T2* 7.8 ± 8.1, P = 0.575. Rest Air-MBF was 0.88 ± 0.40 ml/min/g vs. O 2 -MBF 0.95 ± 0.45, P = 0.168 and hyperaemic Air-MBF 3.46 ± 1.67 vs. O 2 -MBF 3.35 ± 2.05, P = 0.821. In patients, ischaemic region change in BOLD Air-T2* was 1.1 ± 6.6 ms vs. O 2 -T2* 2.7 ± 8.2ms, P = 0.583 compared to Air-T2* 11.2 ± 8.7 vs. O 2 -T2* 2.9 ± 2.5, P = 0.004 in remote myocardium. Remote Air-MBF was 0.81 ± 0.19 vs. O 2 -MBF 0.76 ± 0.15, P = 0.087 and hyperaemic Air-MBF 1.31 ± 0.047 vs. O 2 -MBF 1.50 ± 0.53, P = 0.249; whilst ischaemic region Air-MBF was 0.83 ± 0.20 vs. O 2 -MBF 0.85 ± 0.28, P = 0.725 and hyperaemic Air-MBF 1.26 ± 0.055 vs. O 2 -MBF 1.35 ± 0.59, P = 0.407. Rest ischaemic Air-E was 0.69 ± 0.14 vs. O 2 -E 0.66 ± 0.17, P = 0.408 and remote Air-E was 0.73 ± 0.13 vs. O 2 -E 0.64 ± 0.15, P = 0.044. Ischaemic region Air-PS was 0.67 ± 0.38 ml/min/g vs. O 2 -PS 0.58 ± 0.32, P = 0.227; whilst remote region Air-PS was 0.72 ± 0.38 vs. O 2 -PS 0.53 ± 0.32, P = 0.024. Invasively there was an increase in rest transit time 0.69 ± 0.35 vs. 0.97 ± 0.50, P = 0.001, resistance index 51.0 ± 26.6 vs. 75.0 ± 38.0, P Conclusion Supplemental high-flow oxygen (and hence hyperoxaemia) results in increased microvascular resistance in patients with severe CAD, demonstrated during invasive coronary physiology studies. We have also shown with novel CMR techniques that, in patients with severe CAD, whilst there is no difference in absolute myocardial blood flow, high-flow supplemental oxygen results in a reduction in first-pass extraction fraction and capillary permeability-surface area product. This results in a reduction in myocardial oxygenation in the remote, non-ischaemic, myocardium. Supplemental high-flow oxygen should therefore be avoided in patients who are not hypoxic.
- Published
- 2016
91. Dreams of Accumulation: The Economics of SF Video Games
- Author
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David M. Higgins
- Subjects
Literature and Literary Theory ,Multimedia ,05 social sciences ,050602 political science & public administration ,0507 social and economic geography ,Sociology ,computer.software_genre ,050701 cultural studies ,computer ,0506 political science - Published
- 2016
92. Coming to Terms with SF
- Author
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David M. Higgins
- Subjects
Literature and Literary Theory - Published
- 2016
93. Relationship of vitamin D deficiency to clinical outcomes in critically ill patients
- Author
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Paul E. Wischmeyer, Daren K. Heyland, Kelly Queensland, David M. Higgins, Stefan Sillau, and Alexandra Sufit
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Critical Illness ,Population ,Medicine (miscellaneous) ,Disease ,vitamin D deficiency ,law.invention ,Patient Admission ,law ,Cause of Death ,Confidence Intervals ,Prevalence ,Medicine ,Humans ,Prospective Studies ,Vitamin D ,Prospective cohort study ,education ,Cause of death ,Aged ,Proportional Hazards Models ,education.field_of_study ,Cross Infection ,Nutrition and Dietetics ,Proportional hazards model ,business.industry ,Length of Stay ,Middle Aged ,medicine.disease ,Vitamin D Deficiency ,Intensive care unit ,Confidence interval ,Patient Discharge ,Intensive Care Units ,Treatment Outcome ,Female ,business - Abstract
Despite the numerous disease conditions associated with vitamin D deficiency in the general population, the relationship of this deficiency to outcome in critically ill patients remains unclear. The objective of this study is to determine the burden of vitamin D deficiency in intensive care unit (ICU) patients and determine if it is associated with poor patient outcomes.The authors conducted an analysis of samples collected from a prospective study of 196 patients admitted to a medical/surgical ICU in a tertiary care hospital. They measured serum 25-hydroxyvitamin D at admission and up to 10 days following admission and followed patients prospectively for 28-day outcomes.Of analyzable patients, 50 (26%) were deficient (≤30 nmol/L) and 109 (56%) were insufficient (30 and ≤60 nmol/L). Baseline 25(OH)D levels decreased significantly in all patients after 3 days in the ICU and remained significantly lower through 10 days (P.001). 25(OH)D status was not significantly associated with 28-day all-cause mortality (hazard ratio [HR], 0.89; 95% confidence interval, [CI] 0.37-2.24). Higher levels of 25(OH)D were associated with a shorter time-to-alive ICU discharge (HR, 2.11; 95% CI, 1.27-3.51). 25(OH)D-deficient patients showed a nonstatistically significant trend toward a higher infection rate (odds ratio [OR], 3.20; 95% CI, 0.784-13.07; P = .11) compared with patients with sufficient levels of 25(OH)D.This study demonstrates significant decreases in vitamin D status over the duration of the patient's ICU stay. Low levels of vitamin D are associated with longer time to ICU discharge alive and a trend toward increased risk of ICU-acquired infection.
- Published
- 2012
94. Robust myocardial T2 and T2* mapping at 3T
- Author
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Marc Kouwenhoven, Ananth Kidambi, Arshad Zaman, John P Greenwood, Sven Plein, and David M. Higgins
- Subjects
Medicine(all) ,lcsh:Diseases of the circulatory (Cardiovascular) system ,medicine.medical_specialty ,Radiological and Ultrasound Technology ,Image quality ,business.industry ,Myocardial hemorrhage ,T2 mapping ,Shim (magnetism) ,lcsh:RC666-701 ,Poster Presentation ,Healthy volunteers ,Medicine ,Radiology, Nuclear Medicine and imaging ,B0 shimming ,Cardiology and Cardiovascular Medicine ,business ,Nuclear medicine ,Image based ,Angiology - Abstract
Summary Myocardial hemorrhage can be assessed implementing T2 and T2* mapping techniques, however robust myocardial T2 and T2* mapping is challenging at 3T. The goal of this study was to test T2 and T2* myocardial mapping techniques at 3T, with potential improvement in image quality on a system employing B1 shimming, with two methods of for B0 shimming. Background Hemorrhage in the core of acute myocardial infarction (AMI) and area at risk appear to be markers of prognosis, enabling targeted therapy and potentially changing outcome. Myocardial T2 and T2* mapping have been used to detect such tissue changes at 1.5T. Such investigation at 3T is challenging due to additional susceptibility variation (e.g. inferolateral artefact at the heart-lungliver interface). We studied T2 and T2* myocardial mapping techniques at 3T on a system employing B1 shimming, with two methods of B0 shimming. Methods Fifteen volunteers and three STEMI patients were scanned on a 3T Philips Achieva TX system with a 32channel cardiac coil. Triggered, single breath-hold, multi-echo sequences were employed from which T2* and T2 maps were calculated. For the T2 map, the shot of 24 refocused spin echoes was subdivided into six groups, with a linear k-space order within each group contributing to a separate k-space. This strategy allows data acquisition within a breath hold. The echoes used for the centre of k-space for each image/group had consistent parity. Conventional first-order volume B0 shimming (over a cuboid encompassing the whole heart and descending aorta, from which the on-resonance signal is maximised) was compared with image based (IB) B0 shimming, for which first- and second-order field adjustments are calculated from B0 maps, to maximise B0 map homogeneity over an arbitrarily-shaped volume prescribed by the user which can be drawn around the heart (ShimTool; Schar et al MRM 2010). In all cases, septal, anterior and posterior ROIs were manually drawn to obtain average T2 or T2* values. Results Figure 1 shows typical T2 and T2* maps obtained in healthy volunteers. T2 and T2* values are reported in Table 1. In 9 of the total of 15 volunteers, IB shimming reduced T2* map heterogeneity, particularly in the inferolateral wall. In the remaining 6 volunteers, conventional volume shim and IB shimming performed equally. For the T2 mapping, no difference in artefact power between conventional volume shim and IB B0 shimming was detected, although homogeneity improved away from susceptibility artefact. The patient data reflected a similar pattern with additional increase in T2 and T2* values in the affected MI territory.
- Published
- 2012
95. 129 Automatic Maximal Resolution Heart Rate Adaptive Stress Perfusion Imaging: Cardiovascular Magnetic Resonance Study at 3.0T
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David P Ripley, Ananth Kidambi, John P Greenwood, Gavin Bainbridge, Adam K McDiarmid, Akhlaque Uddin, Sven Plein, and David M. Higgins
- Subjects
medicine.diagnostic_test ,business.industry ,Image quality ,Magnetic resonance imaging ,k-space ,Myocardial perfusion imaging ,Temporal resolution ,Heart rate ,medicine ,Cardiology and Cardiovascular Medicine ,business ,Nuclear medicine ,Perfusion ,Image resolution - Abstract
Introduction Myocardial perfusion cardiovascular magnetic resonance (CMR) with vasodilator stress has high diagnostic accuracy for the detection of coronary artery disease (CAD). Current CMR perfusion pulse sequences use fixed acquisition parameters designed to acquire at least three slices heart beat and optimised for the heart rates that occur during pharmacological stress.In patients with lower heart rates, there can therefore be a significant amount of unused imaging time ([Figure 1][1]). In patients with higher heart rates, acquisition with fixed parameters may not be possible at every heart beat. A more flexible acquisition scheme could optimise acquisition parameters specifically for each patient and heart rate with potential improvements in image quality or temporal resolution. The aim of this study was to assess the feasibility of a perfusion pulse sequence which adapts to the heart rate, maximising imaging time and acquired in-plane spatial resolution. ![Abstract 129 Figure 1][2] Abstract 129 Figure 1 A: Fixed resolution pulse sequence and B: Adaptive resolution pulse sequence with acquisition duration maximised for heart rate. Blue: Pre-pulse; PD – Preparation pulse Delay time; k: true centre of K space Methods A new perfusion method, which automatically adapts the acquisition duration to maximise spatial resolution whist maintaining 3 slice imaging at every heart beat was developed ([Figure 1][1]). Ten healthy volunteers (mean age 21.5 ± 1.3 years) and two patients (mean 70 years) underwent adenosine stress and rest perfusion CMR on two separate occasions using a 3.0 T whole body scanner and dedicated 32 channel cardiac coil. On one occasion, a conventional “fixed” resolution perfusion sequence was used (3 short axis slices, SENSE acceleration, acquired in-plane resolution of 2.42 × 2.4 mm). On a second occasion, the adaptive method was used. ![Abstract 129 Figure 2][2] Abstract 129 Figure 2 Example perfusion first pass perfusion mid-slice images A: standard optimised fixed resolution protocol with acquired resolution of 2.42 x 2.42 mm and B: adaptive resolution protocol maximising imaging time with acquired resolution of 1.74 x 1.74 mm revealing less dark rim artefact Images were evaluated blinded to the sequence and image quality graded (1 = high, 2 = adequate, 3 = poor, 4 = unusable) and DRA was measured with electronic callipers at standardised windows settings. Results Adaptive perfusion CMR was feasible in all subjects. Mean stress heart rate (HR) was 89 ± 11 in the fixed resolution group and 90 ± 18 in the adaptive resolution group. The standard perfusion sequence acquired in-plane resolution was 2.42 mm2 and the mean HR adaptive sequence resolution was 1.91 × 1.91 mm ± 0.41 (range 1.53–2.89)(p = 0.001). In two cases the stress HR was too high for alternate R-R interval imaging with the fixed resolution sequence resulting in alternate heart beat imaging. This did not occur with the adaptive sequence which adjusted the resolution was adapted (to 2.84 and 2.89 mm2 respectively). The mean DRA width was 3.0 ± 0.6 mm (95% CI: 2.57–3.51) with the standard perfusion sequence and 2.1 ± 0.6 mm (95% CI: 1.65–2.57) with the adaptive sequence (p < 0.001) ([Figure 2][3]). There was no statistical difference in median image quality score. Discussion Optimising the use of available imaging time during CMR myocardial perfusion imaging with heart rate adaptive shot acquisition duration is feasible and improves the acquired resolution and reduces dark rim artefact whilst maintaining image quality. The effect on diagnostic performance of perfusion CMR should be investigated. [1]: #F1 [2]: pending:yes [3]: #F2
- Published
- 2014
96. Local pulmonary immunotherapy with siRNA targeting TGFβ1 enhances antimicrobial capacity in Mycobacterium tuberculosis infected mice
- Author
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Joaquin Sanchez-Campillo, Mercedes Gonzalez-Juarrero, David M. Higgins, Ian M. Orme, Eric J. Lee, and Adrian G. Rosas-Taraco
- Subjects
Microbiology (medical) ,Tuberculosis ,medicine.medical_treatment ,Immunology ,Pharmacology ,Lymphocyte Activation ,Microbiology ,Article ,Mycobacterium tuberculosis ,Transforming Growth Factor beta1 ,Mice ,Immune system ,medicine ,Gene silencing ,Animals ,RNA, Small Interfering ,Lung ,Tuberculosis, Pulmonary ,Mice, Knockout ,biology ,Immunotherapy ,Th1 Cells ,medicine.disease ,biology.organism_classification ,Interleukin-10 ,Interleukin 10 ,Infectious Diseases ,medicine.anatomical_structure ,Knockout mouse ,Cytokines - Abstract
In this study we demonstrate that it is possible to shift the immune system during a chronic infection with Mycobacterium tuberculosis. TGFβ and IL10 cytokines inhibit the Th1 response during chronic pulmonary infection with Mycobacterium tuberculosis. We show that intrapulmonary delivery of siRNA targeting TGFβ1 is able to reduce the pulmonary bacillary load in mice chronically infected with Mycobacterium tuberculosis: an effect that appears to be partly dependent on IL10 expression. To demonstrate this, we induced gene silencing of tgfβ1 in the lungs of wild type and IL10 knockout mice using a non-invasive aerosolized intrapulmonary delivery of siRNA targeting TGFβ1 Five days after the last treatment with siRNA, the levels of tgfb1 transcripts and TGFβ1 protein were reduced when compared with control groups treated with RNase free water or non-targeting siRNA. Mice treated with siRNA also had increased expression of the antimicrobial mediators (NO and iNOS) which effectively reduced the bacterial load by 0.17 and 0.47 log(10) in C57BL/6 and IL10 KO mice respectively when compared with their respective control mice. More importantly, the bacterial load in siRNA treated IL10 KO mice four weeks after the last treatment remained 0.32 log(10) lower than in control mice.
- Published
- 2010
97. 'Trick or treat' the misrepresentation of American beef exports in Britain during the late nineteenth century
- Author
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David M. Higgins and Dev Gangjee
- Subjects
History ,Business, Management and Accounting (miscellaneous) - Abstract
This article examines the misrepresentation of American beef in the British market between c. 1890 and c. 1913. We examine the complaints voiced by British consumers, producers, and retailers and we discuss the response of the British government and the United States Department of Agriculture. A new dataset is employed to calculate the price premiums that could be earned from the misrepresentation of beef according to geographic origin. While considerable premiums could be earned by "passing-off" American beef as British in the 1890s, these premiums declined during the 1900s. Particular emphasis is placed on the inability of the British government to act unilaterally on meat marking. This article also considers origin as a means of distinguishing between categories of nonbranded goods. Yet "origin" has many dimensions. Not only does it indicate provenance, it sometimes signals quality associated with provenance while also serving as the basis for protectionist responses. This article therefore contributes to the broader debates surrounding origin marking as a commercial and legal phenomenon. © The Author 2010.
- Published
- 2010
98. Non-invasive diagnosis of early pulmonary disease in PECAM-deficient mice using infrared pulse oximetry
- Author
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John Gilchrist, Alan R. Schenkel, William A. Muller, Mercedes Gonzalez-Juarerro, David M. Higgins, Marta Lishnevsky, Ian M. Orme, and Merideth A. Early
- Subjects
Pathology ,medicine.medical_specialty ,Infrared Rays ,Clinical Biochemistry ,Article ,Pathology and Forensic Medicine ,Pulmonary function testing ,Mice ,Fibrosis ,medicine ,Animals ,Oximetry ,Diffuse alveolar damage ,Molecular Biology ,Oxygen saturation (medicine) ,Lung ,medicine.diagnostic_test ,business.industry ,Respiratory disease ,Interstitial lung disease ,medicine.disease ,Immunohistochemistry ,Mice, Mutant Strains ,Oxygen ,Platelet Endothelial Cell Adhesion Molecule-1 ,Pulse oximetry ,Disease Models, Animal ,medicine.anatomical_structure ,Early Diagnosis ,business ,Lung Diseases, Interstitial - Abstract
Pulse oximetry is a common tool for detecting reduced pulmonary function in human interstitial lung diseases. It has not previously been used in a mouse model of interstitial lung disease. Further, platelet endothelial cell adhesion molecule deficient mice rarely show symptoms until disease is advanced. Using blood oxygen saturation, different stages of disease could be identified in a non-invasive manner. These stages could be correlated to pathology. Collagen deposition, using Picrosirius Red, did correlate with blood oxygen saturation. These studies are the first to show the use of an infrared pulse oximetry system to analyze the progression of a fibrotic interstitial lung disease in a mouse model of the human diseases. Further, these studies show that an early alveolar damage/enlargement event precedes the fibrosis in this mouse model, a stage that represents the best targets for disease analysis and prevention. This stage does not have extensive collagen deposition. Most importantly, targeting this earliest stage of disease for therapeutic intervention may lead to novel treatment for human disease.
- Published
- 2009
99. Intrapulmonary delivery of XCL1-targeting small interfering RNA in mice chronically infected with Mycobacterium tuberculosis
- Author
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Adrian G. Rosas-Taraco, Ian M. Orme, David M. Higgins, Joaquin Sanchez-Campillo, Mercedes Gonzalez-Juarrero, and Eric J. Lee
- Subjects
Pulmonary and Respiratory Medicine ,Small interfering RNA ,Chemokine ,T-Lymphocytes ,Clinical Biochemistry ,Microbiology ,Mycobacterium tuberculosis ,Interferon-gamma ,Mice ,Fibrosis ,Administration, Inhalation ,medicine ,Gene silencing ,Animals ,Humans ,Interferon gamma ,Tissue Distribution ,Gene Silencing ,RNA, Small Interfering ,Molecular Biology ,Lung ,Tuberculosis, Pulmonary ,Aerosols ,biology ,Cell Biology ,Articles ,medicine.disease ,biology.organism_classification ,Chemokines, C ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Immunology ,biology.protein ,Female ,medicine.drug ,XCL1 - Abstract
Mice infected for 60 days with Mycobacterium tuberculosis were treated with aerosolized XCL1-targeting small interfering RNA (siRNA) to induce local and transient suppression of XCL1/lymphotactin (an important chemokine in tuberculoid granuloma formation). The local pulmonary siRNA therapy resulted in a 50% decrease in the total amount of xcl1 gene transcripts at 3 days, and 40 to 50% protein suppression 3 and 5 days after treatment. Reduced XCL1 expression in the lungs was associated with decreased numbers of T lymphocytes, reduction in the IFN-gamma response, disorganized granulomatous lesions, and higher fibrosis when compared with control mice treated with either PBS or nontargeting siRNA. This indicates that a transient but strong modulation of the production of XCL1 in the lungs has a significant effect on the influx of IFN-gamma-secreting T cells, as well as local pathology, but without significantly altering containment of the infection.
- Published
- 2008
100. Lack of IL-10 alters inflammatory and immune responses during pulmonary Mycobacterium tuberculosis infection
- Author
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Adrian G. Rosas-Taraco, David M. Higgins, Ian M. Orme, Mercedes Gonzalez-Juarrero, Joaquin Sanchez-Campillo, and Eric J. Lee
- Subjects
Microbiology (medical) ,Tuberculosis ,medicine.medical_treatment ,Immunology ,Inflammation ,Biology ,Lymphocyte Activation ,Microbiology ,Mycobacterium tuberculosis ,Mice ,Immune system ,Immunity ,Transforming Growth Factor beta ,medicine ,Immune Tolerance ,Animals ,Lung ,Tuberculosis, Pulmonary ,Mice, Knockout ,Th1 Cells ,medicine.disease ,biology.organism_classification ,Flow Cytometry ,Lymphocyte Subsets ,Interleukin-10 ,Interleukin 10 ,Infectious Diseases ,Cytokine ,Disease Progression ,Cytokines ,Tumor necrosis factor alpha ,Female ,medicine.symptom - Abstract
Summary Failure of mice to produce IL-10 has no effect on the bacterial burden of Mycobacterium tuberculosis infection in the lungs over the first 4–5 months of the disease. We show here that after 185 days of the infection, IL-10 gene disrupted (IL-10 KO) mice showed evidence of bacterial regrowth, began to show signs of wasting, and were moribund. We assessed the status of the acquired immune response and compared the lung lymphocyte cell populations, as well as the expression of Th1 (IL-12 and IFNγ) and immunosuppressive (TGFβ) cytokines, between IL-10 KO and wild type mice. The results demonstrated that at 60 days of the infection in the absence of IL-10 there was an increased expression of Th1 type immunity and an overall lack of control of the inflammatory responses. After 185 days of the infection, in the absence of IL-10 there was excessive pulmonary inflammation and increased expression of inflammatory cytokine TNFα. These results imply therefore that IL-10 plays a central role in dampening of the Th1 response and protection against chronic lung inflammation in the M. tuberculosis infected lung, and the complete removal of this regulatory component eventually leads to disease progression.
- Published
- 2008
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