207 resultados para Analysis of the discourse
Resumo:
Although a substantial corpus of digital materials is now available to scholarship across the disciplines, objective evidence of their use, impact, and value, based on a robust assessment, is sparse. Traditional methods of assessment of impact in the humanities, notably citation in scholarly publications, are not an effective way of assessing impact of digital content. These issues are problematic in the field of Digital Humanities where there is a need to effectively assess impact to justify its continued funding and existence. A number of qualitative and quantitative methods exist that can be used to monitor the use of digital resources in various contexts although they have yet to be applied widely. These have been made available to the creators, managers, and funders of digital content in an accessible form through the TIDSR (Toolkit for the Impact of Digital Scholarly Resources) developed by the Oxford Internet Institute. In 2011, the authors of this article developed the SPHERE project (Stormont Parliamentary Hansards: Embedded in Research and Education) specifically to use TIDSR to evaluate the use and impact of The Stormont Papers, a digital collection of the Hansards of the Stormont Northern Irish Parliament from 1921 to 1972. This article presents the methodology, findings, and analysis of the project. The authors argue that TIDSR is a useful and, critically, transferrable method to understand and increase the impact of digital resources. The findings of the project are modified into a series of wider recommendations on protecting the investment in digital resources by increasing their use, value, and impact. It is reasonable to suggest that effectively showing the impact of Digital Humanities is critical to its survival.
Resumo:
To investigate the association between polymorphisms of the aldose reductase gene and diabetic nephropathy in both Type 1 and Type 2 diabetes mellitus, and to carry out a meta-analysis of published results.
Resumo:
BACKGROUND: Obesity has emerged as a risk factor for the development of asthma and it may also influence asthma control and airways inflammation. However, the role of obesity in severe asthma remains unclear. OBJECTIVE: To explore the association between obesity (defined by BMI) and severe asthma. METHODS: Data from the National Registry for dedicated UK Difficult Asthma Services were used to compare patient demographics, disease characteristics and healthcare utilisation between three body mass index (BMI) categories (normal weight: 18.5 -24.99, overweight: 25 -29.99, obese: =30) in a well characterised group of severe asthmatic adults. RESULTS: The study population consisted of 666 severe asthmatics with a median BMI of 29.8 (interquartile range 22.5 -34.0). The obese group exhibited greater asthma medication requirements in terms of maintenance corticosteroid therapy (48.9% versus 40.4% and 34.5% in the overweight and normal weight groups, respectively), steroid burst therapy and short-acting ß2-agonist (SABA) use per day. Significant differences were seen with gastro-oesophageal reflux disease (GORD) (53.9% versus 48.1% and 39.7% in the overweight and normal weight groups, respectively) and proton pump inhibitor (PPI) use. Bone density scores were higher in the obese group, whilst pulmonary function testing revealed a reduced FVC and raised Kco. Serum IgE levels decreased with increasing BMI and the obese group were more likely to report eczema, but less likely to have a history of nasal polyps. CONCLUSIONS: Severe asthmatics display particular characteristics according to BMI that support the view that obesity associated severe asthma may represent a distinct clinical phenotype.1Royal Brompton Hospital, London, UK;2Department of Computing, Imperial College, UK3Airways Disease, National Heart & Lung Institute, Imperial College, UK;4Centre for infection and immunity, Queen's University of Belfast, UK;5University of Leicester, UK;6The University of Manchester and University Hospital of South Manchester, UK;7Birmingham Heartlands Hospital, University of Birmingham, UK;8Gartnavel General Hospital, University of Glasgow, UK;9Glasgow Royal Infirmary, Glasgow, UKCorrespondence: Dr Andrew N. Menzies-Gow, Royal Brompton Hospital, Fulham Road, London SW3 6HP.
Resumo:
This article examines the Council of Europe’s recent Convention on Preventing and Combating Violence against Women. The focus of this paper is on the specific issue of domestic violence. The article seeks to place the Convention in the context of other developments as regards the analysis of domestic violence as a human rights issue.
Resumo:
To infect their mammalian hosts, Fasciola hepatica larvae must penetrate and traverse the intestinal wall of the duodenum, move through the peritoneum, and penetrate the liver. After migrating through and feeding on the liver, causing extensive tissue damage, the parasites move to their final niche in the bile ducts where they mature and produce eggs. Here we integrated a transcriptomics and proteomics approach to profile Fasciola secretory proteins that are involved in host-pathogen interactions and to correlate changes in their expression with the migration of the parasite. Prediction of F. hepatica secretory proteins from 14,031 expressed sequence tags (ESTs) available from the Wellcome Trust Sanger Centre using the semiautomated EST2Secretome pipeline showed that the major components of adult parasite secretions are proteolytic enzymes including cathepsin L, cathepsin B, and asparaginyl endopeptidase cysteine proteases as well as novel trypsin-like serine proteases and carboxypeptidases. Proteomics analysis of proteins secreted by infective larvae, immature flukes, and adult F. hepatica showed that these proteases are developmentally regulated and correlate with the passage of the parasite through host tissues and its encounters with different host macromolecules. Proteases such as FhCL3 and cathepsin B have specific functions in larvae activation and intestinal wall penetration, whereas FhCL1, FhCL2, and FhCL5 are required for liver penetration and tissue and blood feeding. Besides proteases, the parasites secrete an array of antioxidants that are also highly regulated according to their migration through host tissues. However, whereas the proteases of F. hepatica are secreted into the parasite gut via a classical endoplasmic reticulum/Golgi pathway, we speculate that the antioxidants, which all lack a signal sequence, are released via a non-classical trans-tegumental pathway.
Resumo:
Cathepsin L proteases secreted by the helminth pathogen Fasciola hepatica have functions in parasite virulence including tissue invasion and suppression of host immune responses. Using proteomics methods alongside phylogenetic studies we characterized the profile of cathepsin L proteases secreted by adult F. hepatica and hence identified those involved in host-pathogen interaction. Phylogenetic analyses showed that the Fasciola cathepsin L gene family expanded by a series of gene duplications followed by divergence that gave rise to three clades associated with mature adult worms (Clades 1, 2, and 5) and two clades specific to infective juvenile stages (Clades 3 and 4). Consistent with these observations our proteomics studies identified representatives from Clades 1, 2, and 5 but not from Clades 3 and 4 in adult F. hepatica secretory products. Clades 1 and 2 account for 67.39 and 27.63% of total secreted cathepsin Ls, respectively, suggesting that their expansion was positively driven and that these proteases are most critical for parasite survival and adaptation. Sequence comparison studies revealed that the expansion of cathepsin Ls by gene duplication was followed by residue changes in the S2 pocket of the active site. Our biochemical studies showed that these changes result in alterations in substrate binding and suggested that the divergence of the cathepsin L family produced a repertoire of enzymes with overlapping and complementary substrate specificities that could cleave host macromolecules more efficiently. Although the cathepsin Ls are produced as zymogens containing a prosegment and mature domain, all secreted enzymes identified by MS were processed to mature active enzymes. The prosegment region was highly conserved between the clades except at the boundary of prosegment and mature enzyme. Despite the lack of conservation at this section, sites for exogenous cleavage by asparaginyl endopeptidases and a Leu-Ser[downward arrow]His motif for autocatalytic cleavage by cathepsin Ls were preserved.
Resumo:
The nematodes Trichinella spiralis and Trichinella pseudospiralis are both intracellular parasites of skeletal muscle cells and induce profound alterations in the host cell resulting in a re-alignment of muscle-specific gene expression. While T. spiralis induces the production of a collagen capsule surrounding the host-parasite complex, T. pseudospiralis exists in a non-encapsulated form and is also characterised by suppression of the host inflammatory response in the muscle. These observed differences between the two species are thought to be due to variation in the proteins excreted or secreted (ES proteins) by the muscle larva. In this study, we use a global proteomics approach to compare the ES protein profiles from both species and to identify individual T. pseudospiralis proteins that complement earlier studies with T. spiralis. Following two-dimensional gel electrophoresis, tandem mass spectrometry was used to identify the peptide spots. In many cases identification was aided by the determination of partial peptide sequence from selected mass ions. The T. pseudospiralis spots identified included the major secreted glycoproteins and the secreted 5'-nucleotidase. Furthermore, two major groups of T. spiralis-specific proteins and several T. pseudospiralis-specific proteins were identified. Our results demonstrate the value of proteomics as a tool for the identification of ES proteins that are differentially expressed between Trichinella species and as an aid to identifying key parasite proteins that are involved in the host-parasite interaction. The value of this approach will be further enhanced by data arising out the current T. spiralis genome sequencing project.
Resumo:
Trichinella spiralis is an intracellular nematode parasite of mammalian skeletal muscle. Infection of the muscle cell leads to the formation of a host-parasite complex that results in profound alterations to the host cell and a re-alignment of muscle-specific gene expression. The role of parasite excretory-secretory (ES) proteins in mediating these effects is currently unknown, largely due to the difficulty in identifying and assigning function to individual proteins. In this study, a global proteomics approach was used to analyse the ES proteins from T. spiralis muscle larvae. Following 2-DE of ES proteins,MALDI-TOF-MS and LC-MS/MS were used to identify the peptide spots. Specific Trichinella EST databases were assembled and used to analyse the data. Despite the current absence of a Trichinella genome-sequencing project, 43 out of 52 protein spots analysed were identified and included the major secreted glycoproteins. Other novel proteins were identified from matches with sequences in the T. spiralis database. Our results demonstrate the value of proteomics as a tool for the identification of Trichinella ES proteins and in the study of the molecular mechanism underpinning the formation of the host-parasite complex during Trichinella infections.
Jamestown Island: a Comprehensive Analysis of the the Jamestown Archaeological Assessment, 1992-1996
Resumo:
Rhizosphere microorganisms play an important role in soil carbon flow, through turnover of root exudates, but there is little information on which organisms are actively involved or on the influence of environmental conditions on active communities. In this study, a (CO2)-C-13 pulse labelling field experiment was performed in an upland grassland soil, followed by RNA-stable isotope probing (SIP) analysis, to determine the effect of liming on the structure of the rhizosphere microbial community metabolizing root exudates. The lower limit of detection for SIP was determined in soil samples inoculated with a range of concentrations of C-13-labelled Pseudomonas fluorescens and was found to lie between 10(5) and 10(6) cells per gram of soil. The technique was capable of detecting microbial communities actively assimilating root exudates derived from recent photo-assimilate in the field. Denaturing gradient gel electrophoresis (DGGE) profiles of bacteria, archaea and fungi derived from fractions obtained from caesium trifluoroacetate (CsTFA) density gradient ultracentrifugation indicated that active communities in limed soils were more complex than those in unlimed soils and were more active in utilization of recently exuded C-13 compounds. In limed soils, the majority of the community detected by standard RNA-DGGE analysis appeared to be utilizing root exudates. In unlimed soils, DGGE profiles from C-12 and C-13 RNA fractions differed, suggesting that a proportion of the active community was utilizing other sources of organic carbon. These differences may reflect differences in the amount of root exudation under the different conditions.
Resumo:
A joint concern with multidimensionality and dynamics is a defining feature of the pervasive use of the terminology of social exclusion in the European Union. The notion of social exclusion focuses attention on economic vulnerability in the sense of exposure to risk and uncertainty. Sociological concern with these issues has been associated with the thesis that risk and uncertainty have become more pervasive and extend substantially beyond the working class. This paper combines features of recent approaches to statistical modelling of poverty dynamics and multidimensional deprivation in order to develop our understanding of the dynamics of economic vulnerability. An analysis involving nine countries and covering the first five waves of the European Community Household Panel shows that, across nations and time, it is possible to identify an economically vulnerable class. This class is characterized by heightened risk of falling below a critical resource level, exposure to material deprivation and experience of subjective economic stress. Cross-national differentials in persistence of vulnerability are wider than in the case of income poverty and less affected by measurement error. Economic vulnerability profiles vary across welfare regimes in a manner broadly consistent with our expectations. Variation in the impact of social class within and across countries provides no support for the argument that its role in structuring such risk has become much less important. Our findings suggest that it is possible to accept the importance of the emergence of new forms of social risk and acknowledge the significance of efforts to develop welfare states policies involving a shift of opportunities and decision making on to individuals without accepting the 'death of social class' thesis.
Resumo:
Poverty research has increasingly focused on persistent income poverty, both as a crucial social indicator and as a target for policy intervention. Such an approach can lead to an identification of a sub-set of poor individuals facing particularly adverse circumstances and/or distinctive problems in escaping from poverty. Here we seek to establish whether, in comparison with cross-sectional measures, persistent poverty measures also provide a better measure of exclusion from a minimally acceptable way of life and relate with other important variables in a logical fashion. Our analysis draws upon the first three waves of the ECHP and shows that a persistent poverty measure does constitute a significant improvement over its cross-sectional counterpart in the explanation of levels of deprivation. Persistent poverty is related to life-style deprivation in a manner that comes close to being uniform across countries. The measure of persistence also conforms to our expectations of how a poverty measure should behave in that, unlike relative income poverty lines, defining the threshold level more stringently enables us to identify progressively groups of increasingly deprived respondents. Overall the persistent poverty measure constitutes a significant advance on cross-sectional income measures. However, there is clearly a great deal relating to the process of accumulation and of erosion of resources, which is not fully captured in the persistent poverty measure. In the absence of such information, there is a great deal to be said for making use of both types of indictors in formulating and evaluating policies while we continue to improve our understanding of longer-term processes.
Resumo:
This paper is concerned with the relationship between household income and life-style deprivation, and their combined impact on households' perceptions of economic strain. It takes as a point of departure findings from a number of European countries showing that the relationship between income and deprivation is weaker than widely assumed and that relative income poverty lines may perform poorly in terms of identifying the most deprived households. It proceeds to examine how far these conclusions about income and deprivation can be generalized to the countries included in the first wave of the European Community Household Panel. Results show that five distinct dimensions of deprivation emerge from an overall European analysis and that these are consistent across individual countries. While a good deal of similarity is observed in the income-deprivation relationship, countries differ in the strength of relationship between income and what is termed 'current liferstyle deprivation' with the relationship being generally weakest in the richer countries. The implications of these findings for the use of relative income poverty lines are developed. Extending this analysis to an assessment of how income and deprivation combine to influence perceptions of economic strain, we show that within-nation reference group processes operating in a uniform manner across countries can account for the bulk of the variation in strain. Cross-national differences can be accounted for by corresponding variation in income and deprivation levels.
Resumo:
In this article, using Ireland where debt issues are of particular salience, as a test case, we seek to locate over-indebtedness and the severity of debt problems in the context of the broader economic circumstances of households. In doing so, we first identify an economically vulnerable segment of households and then explore the debt experience of vulnerable and non-vulnerable households. Our analysis reveals a striking contrast between the debt experiences of less than one in five households defined as economically vulnerable and all others. Financial exclusion, relating to access to a bank account and a credit card, was found to increase debt levels. However, such effects were modest. The impact of economic vulnerability seems to be largely a consequence of its relationship to a wide
range of socio-economic attributes and circumstances. The manner in which a potential debt crisis
unfolds will be shaped by the broader socio-economic structuring of life-chances. Any attempt to
respond to such problems by concentrating on financial exclusion or household behaviour or, indeed,
triggering factors without taking the wider social structuring of economic vulnerability is likely to be
both seriously misguided and largely ineffective.