1,605 research outputs found
A.D. COUSINS Y PETER HOWARTH (Editores): The Cambridge Companion to the Sonnet. Cambridge: Cambridge University Press, 2011.
No full textA.D. COUSINS Y PETER HOWARTH (Editores): The CambridgeCompanion to the Sonnet. Cambridge: Cambridge UniversityPress, 2011
Pine Marten [film]
No full text‘Pine Marten’ is a short 6 minute documentary by Peter Howarth, filmed as Peter's final major project while a BA Wildlife Media student at the University of Cumbria, UK. The film explores the reintroduction of one of Britain’s rarest mammals, the pine marten, into South Cumbria. Peter's film won the regional (North East and the Borders) ‘Saving the Planet’ category of the Royal Television Society Student Television Awards 2024. You can watch the film here: https://www.youtube.com/watch?v=2ik4A24Y9Y
Pharmacological regulation of mast cell mediator release in asthma
No full textThis thesis presents the investigation into the pharmacological regulation of mast cell mediator release in asthma, in vivo. The immediate airway response to inhaled allergen has been used as an in vivo model of mast cell activation in atopic asthma and changes in the circulating levels of histamine in plasma and high molecular weight neutrophil chemotactic activity (NCA) in serum as markers of mast cell activation. Both allergenic reactivity and non-specific bronchial reactivity were found to be determinants of the immediate airway response to allergen, the level of non-specific bronchial reactivity determining the pattern of circulating mediator changes following allergen inhalation challenge. In this respect, changes in serum NCA were more sensitive a marker for mast cell activation than changes in plasma histamine. Changes in plasma histamine were only detectable in patients with relatively unreactive airways to non-specific stimuli, indicative of the greater degree of intrapulmonary mast cell degranulation required in these subjects to produce bronchoconstriction. Plasma histamine changes, when they occurred, were, however, significantly greater outside the variance of the baseline measurements than those changes identified with serum NCA, identifying that plasma histamine changes are a more precise marker of intrapulmonary mast cell activation. These changes in plasma histamine were repeatable both within and between subjects. Although basophil derived histamine was found to be an important determinant of resting plasma histamine levels, basophils were not found to contribute to the immediate increments in histamine following allergen inhalation. Using this model, astemizole, a potent and specific oral H1-receptor antagonist, attenuated the immediate airway response to allergen, without influencing mast cell degranulation. Both inhaled salbutamol and sodium cromoglycate were found to inhibit mast cell degranulation in vivo and inhaled ipratropium bromide, which produced equivalent bronchodilatation to salbutamol, had no significant effect on either the airway or mediator responses to allergen inhalation. Salbutamol was found to be more active, as an inhibitor of immunologically stimulated mast cell mediator release, but the inhaled rather than the oral route, despite dose equivalents producing comparable effects on non-specific bronchial reactivity, illustrating the importance of the mucosal mast cell in the immediate interaction with allergen. Although dose equivalents were not calculated, by inhalation, salbutamol was at least 100 times more potent than sodium cromoglycate in inhibiting immunologically stimulated mast cell degranulation. The relevance of these findings to the model of allergic asthma are discussed and question the role of the mast cell in the genesis of allergen induced airway inflammation and bronchial hyperreactivity in asthma.</p
Repeated high-dose inhalation allergen challenge in asthma
No full textIntroduction:? Inhalation allergen challenge in humans is used to investigate lung pathophysiology and responses to novel therapies. However, the single high-dose allergen challenges that are commonly performed do not mimic repeated symptomatic environmental allergen exposure.Objectives:? To develop and evaluate the safety of a repeated high-dose symptomatic inhalation allergen challenge model.Methods:? Sixteen subjects with atopic asthma were recruited. Each underwent three inhalation allergen challenges using house dust mite (Dermatophagoides pteronyssinus) antigen at 48-h intervals with a target of symptom induction and an early asthmatic reaction fall in forced expiratory volume in 1 s (FEV1) of 15% from baseline.Results:? All of the subjects completed the three-challenge protocol and the target immediate airway bronchoconstrictor response was achieved in all the subjects at all challenges. There were no adverse events recorded. The early asthmatic reaction was similar for the three challenges whether measured as mean maximal fall in FEV1 or mean area under the curve. The late asthmatic reaction was also similar over the three challenges with no evidence of priming or desensitisation. Symptom scores and reliever medication use significantly increased over the time of the challenges. Baseline lung function and reversibility was unchanged 4 days after the last challenge.Conclusion:? We demonstrate that repeated high-dose inhaled house dust mite allergen challenge in human volunteers with mild asthma is safe, repeatable and acceptable. This allows the use of this model in further studies focused on understanding the pathophysiology of allergen induced asthma and the impact of therapeutic interventions.<br/
δ Orionis: Further temporal variability and evidence for small-scale structure in the interstellar medium
No full textWe report here the detection of both spatial and temporal variations in interstellar absorption in the line of sight to δ Orionis. First, we present new high-resolution (R≈110 000) observations of the interstellar D lines of Na i towards both δ Ori A and C. Comparison of these spectra highlights variations in absorption between the two stars, indicative of small-scale spatial structure in the interstellar medium in this direction over distances of less than ≈15 000 au (the projected separation of the two stars). Components with the largest Na i column densities and lowest velocity dispersions are, in general, found to be subject to the greatest differences; in fact the narrowest component detected is only observed in one of the sightlines. This effect has also been reported by Meyer & Blades. Secondly, we present new ultra-high-resolution (R≈900 000) Na i D1 observations and high-resolution (R≈110 000) Ca ii H & K observations of δ Ori A which, through ultra-high-resolution work conducted between 1994 and 2000, has been shown to exhibit a time-variable interstellar Na i absorption component. These new observations, while revealing the further reduction in intensity of the time-variable Na i absorption, indicate constant Ca ii absorption over the same period. This results in a dramatic reduction in the Na°/Ca+ abundance ratio, perhaps indicating the line of sight to be gradually probing a less-dense outer region of an absorbing filament
A new look at the pathogenesis of asthma
No full textAsthma is an inflammatory disorder of the conducting airways that has strong association with allergic sensitization. The disease is characterized by a polarized Th-2 (T-helper-2)-type T-cell response, but in general targeting this component of the disease with selective therapies has been disappointing and most therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms. With the disappointing outcomes of targeting individual Th-2 cytokines or manipulating T-cells, the time has come to re-evaluate the direction of research in this disease. A case is made that asthma has its origins in the airways themselves involving defective structural and functional behaviour of the epithelium in relation to environmental insults. Specifically, a defect in barrier function and an impaired innate immune response to viral infection may provide the substrate upon which allergic sensitization takes place. Once sensitized, the repeated allergen exposure will lead to disease persistence. These mechanisms could also be used to explain airway wall remodelling and the susceptibility of the asthmatic lung to exacerbations provoked by respiratory viruses, air pollution episodes and exposure to biologically active allergens. Variable activation of this epithelial-mesenchymal trophic unit could also lead to the emergence of different asthma phenotypes and a more targeted approach to the treatment of these. It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established.<br/
Supplemental material for The impact of digital health interventions on health-related outcomes in the workplace: A systematic review
No full textSupplemental material for The impact of digital health interventions on health-related outcomes in the workplace: A systematic review by Ana Howarth, Jose Quesada, Jessica Silva, Stephanie Judycki and Peter R Mills in Digital Health</p
MicroRNAs and respiratory diseases
No full textMicroRNAs (miRNA) are a family of endogenous, small, noncoding RNA molecules that modulate physiological and pathological processes by post-transcriptional inhibition of gene expression. They were first recognised as regulators of development in worms and fruitflies. In recent years extensive research has explored their pivotal role in the pathogenesis of human diseases. Over 1000 human miRNAs have been discovered to date, however the biological function and protein targets for the majority remain to be uncovered. Within the respiratory system, miRNAs are important in normal pulmonary development and maintaining lung homeostasis. Recent studies have also begun to reveal that altered miRNA expression profiles may be associated with pathological processes within the lung and lead to the development of various pulmonary diseases ranging from inflammatory diseases to lung cancers. Advancing our understanding of the role of miRNAs in the respiratory system will help provide new perspectives on disease mechanisms and reveal intriguing therapeutic targets and diagnostics for respiratory disorders
Review: David Howarth (2000). Discourse
No full textHOWARTH's book is an accessible, readable and concise overview of theories of and approaches to discourse in the human and social sciences, focusing upon LACLAU and MOUFFE's discourse theory approach. The roots of this approach are described in structuralist and post-structuralist theories including the work of SAUSSURE, LEVI-STRAUSS, DERRIDA and FOUCAULT, as well as the MARXism of ALTHUSSER, GRAMSCI and PECHEUX. The book is mostly even-handed and the author takes great care to make his material accessible. However, critical realist alternatives to poststructuralism receive little attention and issues of agency and subjectivity remain problematic. These issues are part of the wider debate between realism and relativism, the intransigence of which is somewhat downplayed in this book. Nevertheless, HOWARTH has produced a valuable resource which should be welcomed by teachers and students in this field.HOWARTH's book is an accessible, readable and concise overview of theories of and approaches to discourse in the human and social sciences, focusing upon LACLAU and MOUFFE's discourse theory approach. The roots of this approach are described in structuralist and post-structuralist theories including the work of SAUSSURE, LEVI-STRAUSS, DERRIDA and FOUCAULT, as well as the MARXism of ALTHUSSER, GRAMSCI and PECHEUX. The book is mostly even-handed and the author takes great care to make his material accessible. However, critical realist alternatives to poststructuralism receive little attention and issues of agency and subjectivity remain problematic. These issues are part of the wider debate between realism and relativism, the intransigence of which is somewhat downplayed in this book. Nevertheless, HOWARTH has produced a valuable resource which should be welcomed by teachers and students in this field.El libro de HOWARTH es una revisión general accesible, legible y concisa de las teorías y enfoques del discurso en las ciencias sociales y humanas, focalizándose en los enfoques de LACLAU y MOUFFE sobre la teoría del discurso. Las raíces de este enfoque son descritas en las teorías estructuralistas y post estructuralistas, incluyendo el trabajo de SAUSSURE, LEVI-STRAUSS, DERRIDA y FOUCAULT, así como el marxismo de ALTHUSSER, GRAMSCI y PECHEUX. El libro es en su mayor parte imparcial y el autor se esfuerza en hacer accesible el material. Sin embargo, las alternativas crítica realistas al post estructuralismo reciben poca atención y asuntos como la gestión humana y la subjetividad permanecen problemáticos. Estas cuestiones son parte del debate más amplio entre realismo y relativismo, intransigencia del cual es de alguna manera presentada en este libro. Sin embargo, HOWARTH ha producido un recurso valioso el cual debería ser bienvenido para maestros y estudiantes en este campo
Airway inflammation in atopic patients: a comparison of the upper and lower airways
No full textObjective. The purpose of this study was to understand and assess the inflammatory response within the upper and lower airways in patients suffering from both asthma and allergic rhinitis. Study Design. Cross-sectional study. Setting. A laboratory-based study of patients with allergic rhinitis and asthma. Subjects and Methods. Glycol methacrylate resin-embedded specimens from 10 patients with allergic rhinitis and asthma taken from the nose and bronchi were assessed by immunohistochemistry. Monoclonal antibodies directed against specific cell markers for mast cells (AA1), eosinophils (EG2), neutrophils (NOE), and lymphocytes (CD3(+), CD4(+), CD8(+)) were studied. Cells were counted blind (as cells/mm(2)) in the submucosal matrix. Mann-Whitney U test was used for analyses. P values of .05 or lower were considered statistically significant. Results. There was a significant increase in CD4(+) (P = .05) and CD8(+) cell counts (P = .001) in the lower airway compared to the upper airway. There were no differences between the 2 groups in the number of neutrophils, mast cells, eosinophils, and the CD3(+) cell counts. Conclusion. The upper and lower airways have parallel inflammation with possible bidirectional extension of inflammation in patients suffering from asthma and allergic rhinitis. There is increased lymphocytic infiltration in the lower airway, suggesting a possible preponderance for development and maintenance of allergic disease in the lower airway
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