The application of metabolomic biomarker screening tools for improved Bovine Respiratory Disease diagnosis and management

Bovine Respiratory Disease (BRD) is considered to be one of the most significant causes of economic loss in cattle worldwide. The disease has multifactorial aetiology, where viral induced respiratory damage can predispose animals to developing secondary bacterial infections. Accurate identification of viral infected animals prior to the onset of bacterial infection is necessary to reduce the overuse of antimicrobial treatments and minimize further economic losses from reduced production capacity and death. This research focuses on Bovine Parainfluenza Virus Type 3 (BPIV-3), one of the viruses involved in generating BRD. Vaccination measures for BPIV-3 can induce a level of immunity preventing disease progression, however, not all animals respond equally and immunization can complicate disease diagnosis. Alternative diagnostic approaches are required to identify animals which fail to respond to vaccination during infection outbreaks and are therefore likely to be more susceptible to secondary bacterial infections. Mass spectrometry based metabolomics was employed to identify plasma markers capable of differentiating between vaccinated and non-vaccinated calves after challenge with BPIV-3. Differentiation of vaccinated and non-vaccinated study groups (n=6) was possible as early as day 2 post-BPIV-3 challenge up until day 20 using a panel of potential metabolite markers. This study illustrates the potential for metabolomics to provide more detailed information on animal vaccination status that could be used to develop tools for improved herd health management, reduce economic loss through rapid identification and isolation of animals without immune protection (improving herd level immunity) and help reduce the usage of antimicrobial therapeutic treatments in animals.

England, Neo-Latin, and the Continental Journey: Linguistic and Textual Itineraries

This chapter examines the ramifications of continental travel and associated epistolary communication for English poets of the period. It argues that recourse to neo-Latin, the universal language of diplomacy, served not only to establish a sense of shared space—linguistic, cultural, generic—between England and the continent, but also to signal self-conscious differences (climatic, geographical, historical, political) between England and her continental peers. Through an investigation of a range of ‘performances’ on stages that were ‘academic’, poetic, autobiographical, and epistolographic, it assesses the central role of neo-Latin as a language that underwent a series of textual itineraries. These ‘itineraries’ manifest themselves in a number of ways. Neo-Latin as a shared linguistic medium can facilitate, and quite uniquely so, intertextual engagement with the classics, but now ancient Rome, its language, its mythology, its hierarchy of genres, are viewed through a seventeenth-century lens and appropriated by poets in both England and Italy to describe contemporary events, whether personal, or political. Close examination of the neo-Latin poetry of Milton and Marvell reveals, it is argued, a self-fashioning coloured by such textual itineraries and interchanges. The absorption and replication of continental literary and linguistic methodologies (the academic debate; the etymological play of Marinism; the hybridity of neo-Latin and Italian voices) reveal in short a linguistic and textual reciprocity that gave birth to something very new.

Lung Clearance Index in cystic fibrosis subjects treated for Pulmonary Exacerbations

Pulmonary exacerbations are important clinical events for cystic fibrosis (CF) patients. Studies assessing the ability of the lung clearance index (LCI) to detect treatment response for pulmonary exacerbations have yielded heterogeneous results. Here, we conduct a retrospective analysis of pooled LCI data to assess treatment with intravenous antibiotics for pulmonary exacerbations and to understand factors explaining the heterogeneous response.

A systematic literature search was performed to identify prospective observational studies. Factors predicting the relative change in LCI and spirometry were evaluated while adjusting for within-study clustering.

Six previously reported studies and one unpublished study, which included 176 pulmonary exacerbations in both paediatric and adult patients, were included. Overall, LCI significantly decreased by 0.40 units (95% CI -0.60 -0.19, p=0.004) or 2.5% following treatment. The relative change in LCI was significantly correlated with the relative change in forced expiratory volume in 1 s (FEV1), but results were discordant in 42.5% of subjects (80 out of 188). Higher (worse) baseline LCI was associated with a greater improvement in LCI (slope: -0.9%, 95% CI -1.0- -0.4%).

LCI response to therapy for pulmonary exacerbations is heterogeneous in CF patients; the overall effect size is small and results are often discordant with FEV1.

Michael Allen: Close Readings: Essays on Irish Poetry

The late Michael Allen was a member of the famous Belfast Group, and one of the most authoritative critical voices on poetry from Northern Ireland, intimately part of the North’s poetic movement since the early 1960s. He taught at Queen’s University, where he was a colleague of Seamus Heaney and tutor to poets such as Paul Muldoon and Medbh McGuckian. Seamus Heaney called him ‘the reader over my shoulder’. Close Readings brings together interlinked critical writings which have crucially influenced approaches to Irish poetry during the last forty years. The book ends with an extended essay, hitherto unpublished: ‘Doubles, Twins and the Feminine: Development in the Poetry of Michael Longley’.

Close Readings contains a Foreword by Fran Brearton, which relates Michael Allen’s essays to continuing critical and cultural debates. Edna Longley’s Afterword offers a personal view of Allen’s involvement with poetry in Belfast.

Death and Consumer Culture

Among the most veiled and emotionally charged of life’s experiences are those related to death. Given that poetry has long been recognized as an unparalleled means of expressing and understanding the most complex and emotional aspects of life (Sherry and Schouten, 2002), it is of little surprise that few poets regarded as the finest of all wordsmiths have not, since time immemorial, grappled with death.

Recently, within marketing and consumer research, poetry has slowly but progressively come to be recognized as a means by which to understand, express, celebrate, and/or confront that which defies scientific or other more “scholarly” explanation (Canniford, 2012; Wijland, 2011; Sherry and Schouten, 2002). This “poetic turn” has manifest itself most notably within the nascent realm of Consumer Culture Theory (CCT); mainly in poetry reading sessions held—with published chapbooks in hand—in concurrence with the annual CCT symposium. Death-related poetry penned by marketing and consumer researchers has there entered—albeit randomly—the CCT circuit (see, for example: Arnould, 2014; Steinfield, 2014; Gabel, 2013, 2010; Downey, 2011, 2010a, 2010b, 2010c).

This chapter represents the first formal, organized attempt to better understand death-related consumption experience and meaning via the creation and dissemination of original works of poetry. The chapter’s title reflects the broad, eclectic perspective of death and consumption herein pursued. We consider funerary and other—good, service, and ideological—product consumption activities and experiences transpiring in the context of death. We also embrace the notion that death often brutally consumes those dealing with it; a sort of “consumption of consumers by death.” In turn, as vividly expressed in several of the poems in this chapter, consumption acts or experiences and/or memories thereof may be instrumental in coping with “being consumed by death.”

IRS2 and PTEN are key molecules in controlling insulin sensitivity in podocytes

Insulin signaling to the glomerular podocyte is important for normal kidney function and is implicated in the pathogenesis of diabetic nephropathy (DN). This study determined the role of the insulin receptor substrate 2 (IRS2) in this system. Conditionally immortalized murine podocytes were generated from wild-type (WT) and insulin receptor substrate 2-deficient mice (Irs2−/−). Insulin signaling, glucose transport, cellular motility and cytoskeleton rearrangement were then analyzed. Within the glomerulus IRS2 is enriched in the podocyte and is preferentially phosphorylated by insulin in comparison to IRS1. Irs2−/− podocytes are significantly insulin resistant in respect to AKT signaling, insulin-stimulated GLUT4-mediated glucose uptake, filamentous actin (F-actin) cytoskeleton remodeling and cell motility. Mechanistically, we discovered that Irs2 deficiency causes insulin resistance through up-regulation of the phosphatase and tensin homolog (PTEN). Importantly, suppressing PTEN in Irs2−/− podocytes rescued insulin sensitivity. In conclusion, this study has identified for the first time IRS2 as a critical molecule for sensitizing the podocyte to insulin actions through its ability to modulate PTEN expression. This finding reveals two potential molecular targets in the podocyte for modulating insulin sensitivity and treating DN.

Predictive Value of Depressive Symptoms for All-Cause Mortality: Findings From the PRIME Belfast Study Examining the Role of Inflammation and Cardiovascular Risk Markers

OBJECTIVES: To improve understanding about the potential underlying biological mechanisms in the link between depression and all-cause mortality and to investigate the role that inflammatory and other cardiovascular risk factors may play in the relationship between depressive symptoms and mortality.

METHODS: Depression and blood-based biological markers were assessed in the Belfast PRIME prospective cohort study (N = 2389 men, aged 50-59 years) in which participants were followed up for 18 years. Depression was measured using the 10-item Welsh Pure Depression Inventory. Inflammation markers (C-reactive protein [CRP], neopterin, interleukin [IL]-1 receptor antagonist [IL-1Ra], and IL-18) and cardiovascular-specific risk factors (N-terminal pro-b-type natriuretic peptide, midregion pro-atrial natriuretic peptide, midregion pro-adrenomedullin, C-terminal pro-endothelin-1 [CT-proET]) were obtained at baseline. We used Cox proportional hazards modeling to examine the association between depression and biological measures in relation to all-cause mortality and explore the mediating effects.

RESULTS: During follow-up, 418 participants died. Higher levels of depressive symptoms were associated with higher levels of CRP, IL-1Ra, and CT-proET. After adjustment for socioeconomic and life-style risk factors, depressive symptoms were significantly associated with all-cause mortality (hazard ratio = 1.10 per scale unit, 95% confidence interval = 1.04-1.16). This association was partly explained by CRP (7.3%) suggesting a minimal mediation effect. IL-1Ra, N-terminal pro-b-type natriuretic peptide, midregion pro-atrial natriuretic peptide, midregion pro-adrenomedullin, and CT-proET contributed marginally to the association between depression and subsequent mortality.

CONCLUSIONS: Inflammatory and cardiovascular risk markers are associated with depression and with increased mortality. However, depression and biological measures show additive effects rather than a pattern of meditation of biological factors in the association between depression and mortality.

Neolithic and Bronze age migration to Ireland and establishment of the insular Atlantic genome

The Neolithic and Bronze Age transitions were profound cultural shifts catalyzed in parts of Europe by migrations, first of early farmers from the Near East and then Bronze Age herders from the Pontic Steppe. However, a decades-long, unresolved controversy is whether population change or cultural adoption occurred at the Atlantic edge, within the British Isles. We address this issue by using the first whole genome data from prehistoric Irish individuals. A Neolithic woman (3343–3020 cal BC) from a megalithic burial (10.3× coverage) possessed a genome of predominantly Near Eastern origin. She had some hunter–gatherer ancestry but belonged to a population of large effective size, suggesting a substantial influx of early farmers to the island. Three Bronze Age individuals from Rathlin Island (2026–1534 cal BC), including one high coverage (10.5×) genome, showed substantial Steppe genetic heritage indicating that the European population upheavals of the third millennium manifested all of the way from southern Siberia to the western ocean. This turnover invites the possibility of accompanying introduction of Indo-European, perhaps early Celtic, language. Irish Bronze Age haplotypic similarity is strongest within modern Irish, Scottish, and Welsh populations, and several important genetic variants that today show maximal or very high frequencies in Ireland appear at this horizon. These include those coding for lactase persistence, blue eye color, Y chromosome R1b haplotypes, and the hemochromatosis C282Y allele; to our knowledge, the first detection of a known Mendelian disease variant in prehistory. These findings together suggest the establishment of central attributes of the Irish genome 4,000 y ago.

Experiencing Youth Justice and Penality

Much of the recent literature on youth justice has focused on administrative aspects of the system and the socio-political contexts that have led to the ‘production’ of the youthful offender as a subject and locus of intervention. This has largely been driven by the extent to which youth justice has been crafted as a distinct penal sphere, evident in its unyoking from universal children’s services (Muncie and Goldson, 2013) and the establishment of separate agencies to administer and govern this ‘system’ (Souhami, 2014). Driven by policy hyperactivity and a plethora of legislation expanding the reach of the system, for much of the 1990s and 2000s increasing numbers of young people were brought under its gaze.

Particular attention has been paid to the impact of neo-liberal governance on the discourses, rationales and philosophies underpinning contemporary youth justice policy and practice. Writing specifically in the English and Welsh context, several authors have identified that the resulting ‘system’ embodies multiple, contradictory and competing discourses (Muncie, 2006; Fergusson, 2007; Gray, 2013). Within this ‘melting pot’ Fergusson (2007) notes the disjuncture between policy rhetoric, implementation and lived experience and Phoenix (2015) argues that systems-based analyses, much in favour amongst academics, foreclose a wider consideration of questions of what ‘justice’ actually means.

Recent attention towards the perspectives of practitioners working in this sphere has pointed to greater nuances than broader penal narratives suggest (see: Field, 2007; Briggs, 2013; Gray, 2013; Kelly and Armitage, 2015). Yet similar attention has not been given to experiences of youth justice (for an exception see – Phoenix and Kelly, 2013). However, it is precisely young people’s experiences, which would add significantly to current knowledge and potentially bridge the gap between discussions about penal philosophies, how youth justice policies are framed, how they are enacted and how they are experienced.

This chapter provides an overview of recent developments in the field of youth justice and penality in the United Kingdom. The chapter argues that a theoretical focus on macro-level trends (Hannah-Moffat and Lynch, 2012), alongside a narrowly defined research agenda, have largely excluded young people’s experiences of justice and punishment from contemporary analysis. Drawing on young people experiences of different aspects of youth justice in Northern Ireland and beyond, the chapter illuminates what a close understanding of lived experience can add to knowledge. In particular it demonstrates that the effects of interventions can be different to their aims and intentions; and that re-instating the youth experience can add support to calls for greater attention to wider issues of social justice.