The Irish paradigm on the natural progression of hepatitis C virus infection: an investigation in a homogeneous patient population infected with HCV 1b (Review)

The aetiological agent of chronic hepatitis C is the hepatitis C virus. The hepatitis C virus is spread by parenteral transmission of body fluids, primarily blood or blood products. In 1989, after more than a decade of research, HCV was isolated and characterised. The hepatitis C viral genome is a positive-sense, single-stranded RNA molecule approximately 9.4 kb in length, which encodes a polyprotein of about 3100 amino acids. There are 6 main genotypes of HCV, each further stratified by subtype. In 1994, a cohort of women was identified in Ireland as having been iatrogenically exposed to the hepatitis C virus. The women were all young and exposed as a consequence of the receipt of HCV 1b contaminated anti-D immunoglobulin. The source of the infection was identified as an acutely infected female. As part of a voluntary serological screening programme involving 62,667 people, 704 individuals were identified as seropositive for exposure to the hepatitis C virus; 55.4% were found to be positive for the viral genome 17 years after exposure. Of these women 98% had evidence of inflammation, but suprisingly, a remarkable 49% showed no evidence of fibrosis. Clinicopathology and virological analysis has identified associations between viral load and the histological activity index for inflammation, and, between inflammation and levels of the liver enzyme alanine aminotransferase. Infection at a younger age appears to protect individuals from progression to advanced liver disease. Molecular analyses of host immunogenetic elements shows that particular class II human leukocyte associated antigen alleles are associated with clearance of the hepatitis C virus. Additional class II alleles have been identified that are associated with stable viraemia over an extended period of patient follow-up. Although, investigation of large untreated homogeneous cohorts is likely to become more difficult, as the efficacy of anti-viral therapy improves, further investigation of host and viral factors that influence disease progression will help provide an evidence based approach were realistic expectations regarding patient prognosis can be ascertained.

Carbon, nitrogen and lipid content and egg and pellet production of female C. hyperboreus in situ and during incubation experiments

The effects of temperature and food availability on feeding and egg production of the Arctic copepod Calanus hyperboreus were investigated in Disko Bay, western Greenland, from winter to spring 2009. The abundance of females in the near bottom layer and the egg production of C. hyperboreus prior to the spring bloom document that reproduction relies on lipid stores. The maximum in situ egg production (± SE) of 54 ± 8 eggs female/d was recorded in mid-February at chlorophyll a concentrations below 0.1 µg/l, whereas no egg production was observed in mid-April when the spring bloom developed. After reproduction, the females migrated to the surface layer to exploit the bloom and refill their lipid stores. In 2 laboratory experiments, initiated before and during the spring bloom, mature females were kept with and without food at 5 different temperatures ranging from 0 to 10°C and the fecal pellet and egg production were monitored. Food had a clear effect on fecal pellet production but no effect on egg production, while temperature did not have an effect on egg or fecal pellet production in any of the experiments. Analyses of carbon and lipid content of the females before and after the experiments did not reflect any effect of food or temperature in the pre-bloom experiment, whereas in the bloom experiment a clear positive effect of food was detected in female biochemical profiles. The lack of a temperature response suggests a future warmer ocean could be unfavorable for C. hyperboreus compared to smaller Calanus spp. which are reported to exploit minor temperature elevations for increased egg production.

Analysis of the C-SOSI Instrument in a 9-1-1 Telecommunicator Population

Thesis (Master's)--University of Washington, 2016-08

Warfare in the West Highlands and Isles of Scotland, c. 1544-1615

Warfare has long been associated with Scottish Highlanders and Islanders, especially in the period known in Gaelic tradition as ‘Linn nan Creach’ (the ‘Age of Forays’), which followed the forfeiture of the Lordship of the Isles in 1493. The sixteenth century in general is remembered as a particularly tumultuous time within the West Highlands and Isles, characterised by armed conflict on a seemingly unprecedented scale. Relatively little research has been conducted into the nature of warfare however, a gap filled by this thesis through its focus on a series of interconnected themes and in-depth case studies spanning the period c. 1544-1615. It challenges the idea that the sixteenth century and early seventeenth century was a time of endless bloodshed, and explores the rationale behind the distinctive mode of warfare practised in the West Highlands and Isles. The first part of the thesis traces the overall ‘Process of War’. Chapter 1 focuses on the mentality of the social elite in the West Highlands and Isles and demonstrates that warfare was not their raison d'être, but was tied inextricably to chiefs’ prime responsibility of protecting their lands and tenants. Chapter 2 assesses the causation of warfare and reveals that a recurrent catalyst for armed conflict was the assertion of rights to land and inheritance. There were other important causes however, including clan expectation, honour culture, punitive government policies, and the use of proxy warfare by prominent magnates. Chapter 3 takes a fresh approach to the military capacity of the region through analysis of armies and soldiers, and the final thematic chapter tackles the conduct of warfare in the West Highlands and Isles, with analysis of the tactics and strategy of militarised personnel. The second part of this thesis comprises five case studies: the Clanranald, 1544-77; the Colquhouns of Luss and the Lennox, 1592-1603; the MacLeods of Harris and MacDonalds of Sleat, 1594-1601; the Camerons, 1569-1614; and the ‘Islay Rising’, 1614-15. This thesis adopts a unique approach by contextualising the political background of warfare in order to instil a deeper understanding of why early modern Gaelic Scots resorted to bloodshed. Overall, this period was defined by a sharp rise in military activity, followed by an even sharper decline, a trajectory that will be evidenced vividly in the final case study on the ‘Islay Rising’. Although warfare was widespread, it was not unrestrained or continuous, and the traditional image of a region riven by perpetual bloodshed has been greatly exaggerated.

Eighty years 'Owre the Sea': Robert Burns and the early United States of America, c. 1786-1866.

This thesis represents the first extensive critical study of the relationship between Robert Burns and the early United States of America. Spanning literature, history and memory studies, the following chapters take an interdisciplinary approach towards investigating the methods by which Burns and his works rose to prominence and came to be of cultural and literary significance in America. Theoretically, these converging disciplines intersect through a transnational, Atlantic Studies perspective that shifts emphasis from Burns as the 'national poet of Scotland' onto the various socio-cultural connections that facilitated the spread of his work and reputation. In addition to Scottish literary studies, the thesis contributes to the broader fields of Transatlantic, Transnational and American Studies. Previous studies have suggested that Burns's popularity in the early United States might be attributed to his kinship with 'national' American ideals of freedom, egalitarianism and individual liberty. While some of the evidence supports this claim, this thesis argues that it also wrongly assumes a spatiotemporal unity for the nineteenth-century American nation. It concludes by suggesting that future critical studies of the poet must heed the multifarious complexities of 'national' paradigms, pointing the way to further work on the reception and influence of Burns in other 'global' or, indeed, transnational contexts.

Patterns of Play in the Fast attack of F. C. Barcelona, Manchester United and F. C. Internazionale Milano: a Mixed Method Approach

This study aimed to detect and analyse regular patterns of play in fast attack of football teams, through the combination of the sequential analysis technique and semi-structured interviews to experienced first League Portuguese coaches. The sample included 36 games (12 games of the respective national leagues per team) of the F.C. Barcelona, Inter Milan, and Manchester United teams that were coded with the observational instrument tool developed by Sarmento et al. (2010) and the data analysed through sequential analysis with the software SDIS-GSEQ 5.0. Based on the detected patterns, semi-structured interviews were carried out to 8 expert high-performance football coaches and data were analysed through the content analysis technique using the software NVivo 10. The detected patterns of play revealed specific characteristics of the teams under study. The combination of the results of sequential analysis with the qualitative interviews to the professional coaches proved to be very fruitful in this game the analysis of scope, allowing reconcile scientific knowledge with practical interpretation of coaches who develop their tasks in the field.

Successful Treatment Using Simeprevir, Sofosbuvir and Rituximab of a Severe Form of Hepatitis C Virus-related Mixed Cryoglobulinemia with Cardiac Involvement

Numerous extrahepatic manifestations have been reported in hepatitis C virus (HCV) infection, particularly mixed cryoglobulinemia (MC). MC generally responds to clearance of HCV under pegylated-interferon plus ribavirin treatment. New direct-acting antiviral agents have been licensed for HCV under different combinations but have not been studied in severe forms of MC. Here, we present a case report describing a life-threatening form of MC with multivisceral involvement, which was successfully treated with concomitant rituximab, sofosbuvir and simeprevir. In light of the rapid clinical remission associated with sustained virological response and the excellent side-effect profile, this treatment should be considered as a first-line therapy in severe forms of MC.

Graphic satire and the rise and fall of the First British Empire: political prints from the Seven Years' War to the Treaty of Paris, c. 1756-1783

This thesis examines the early stages of the transformation of emblematic political prints into political caricature from the beginning of the Seven Years' War (1756) to the Treaty of Paris, which ended the American Revolutionary War (1783). Both contextual and iconographical issues are investigated in relation to the debates occasioned by Britain's imperial project, which marked a period of dramatic expansion during the Seven Years' War, and ended with the loss of the American colonies, consequently framing this thesis as a study of political prints during the rise and fall of the so-called 'First British Empire'. Previous studies of eighteenth-century political prints have largely ignored the complex and lengthy evolutionary process by which the emblematic mode amalgamated with caricatural representation, and have consequently concluded that political prints excluded emblems entirely by the end of the 1770s. However, this study emphasizes the significance of the Wilkite movement for the promotion and preservation of emblems, and investigates how pictorial political argument was perceived and received in eighteenth-century British society, arguing that wider tastes and opinions regarding the utilization of political prints gradually shifted to accept both modes of representation. Moreover, the marketplace, legal status, topicality, and manufacturing methods of political prints are analyzed in terms of understanding the precarious nature of their consumption and those that endeavoured to engage in political printmaking. The evolution, establishment, and subsequent appropriation of pictorial tropes is discussed from the early modern period to the beginning of the so-called Golden Age of caricature, while tracing the adaptation of representational models in American colonial prints that employed emblems already entrenched in British pictorial political debate. Political prints from the two largest print collections, the British Museum and the Lewis Walpole Library at Yale are consulted, along with a number of eighteenth-century newspapers and periodicals, to develop the earlier research by M. Dorothy George, Charles Press, Herbert Atherton, Diana Donald, Amelia Rauser, and Eirwen Nicholson.

Temporal variation of delta C-13 in particulate organic matter and oyster Crassostrea gigas in Marennes-Oleron Bay (France): Effect of freshwater inflow

The temporal variability of delta(13)C in suspended particulate organic matter (POM) and oyster Crassostrea gigas along a salinity gradient was investigated from May 1992 to September 1993 within the estuarine bay of Marennes-Oleron (France). During this period the mean daily discharge of the Charente River exhibited large seasonal variation, with a high discharge from November 1992 to January 1993. Contrary to that at the river mouth and the marine littoral, delta(13)C in POM and in oysters at mid-estuary was affected by the high flood period. The delta(13)C values of POM decreased in mid-estuary and remained at low levels during the high discharge period, indicating an increasing contribution of terrestrial inputs to the estuarine POM pool. At the same site, a remarkable decrease of delta(13)C in oysters occurred between December 1992 and March 1993 (after a time lag compared to the ambient POM), indicating incorporation of terrestrial organic matter in oyster tissues during the high flood discharge. The lag between the delta(13)C decrease in POM and oysters is attributed to the time needed for oyster tissues to incorporate enough newly terrestrial light carbon to be recognized by the delta(13)C measure (about 1 to 2 mo). This time interval depends on tissue turnover time. The delta(13)C POM decrease (i.e. 1.3 parts per thousand) cannot explain entirely the decrease observed in oysters (i.e. 2.3 parts per thousand). In fact, the pattern exhibited by mid-estuarine oysters can be explained by the increasing contribution of terrestrial organic matter to their feeding, and the inability to preferentially utilize specific components of the estuarine POM that are C-13-enriched.

Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin

International audience

A Staggered Decameric Assembly of Human C-Reactive Protein Stabilized by Zinc Ions Revealed by X-ray Crystallography

International audience