Platelets retain inducible alpha granule secretion by P‐selectin expression but exhibit mechanical dysfunction during trauma‐induced coagulopathy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149281/1/jth14414.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149281/2/jth14414_am.pd

Reading the biomineralized book of life: expanding otolith biogeochemical research and applications for fisheries and ecosystem-based management

Chemical analysis of calcified structures continues to flourish, as analytical and technological advances enable researchers to tap into trace elements and isotopes taken up in otoliths and other archival tissues at ever greater resolution. Increasingly, these tracers are applied to refine age estimation and interpretation, and to chronicle responses to environmental stressors, linking these to ecological, physiological, and life-history processes. Here, we review emerging approaches and innovative research directions in otolith chemistry, as well as in the chemistry of other archival tissues, outlining their value for fisheries and ecosystem-based management, turning the spotlight on areas where such biomarkers can support decision making. We summarise recent milestones and the challenges that lie ahead to using otoliths and archival tissues as biomarkers, grouped into seven, rapidly expanding and application-oriented research areas that apply chemical analysis in a variety of contexts, namely: (1) supporting fish age estimation; (2) evaluating environmental stress, ecophysiology and individual performance; (3) confirming seafood provenance; (4) resolving connectivity and movement pathways; (5) characterising food webs and trophic interactions; (6) reconstructing reproductive life histories; and (7) tracing stock enhancement efforts. Emerging research directions that apply hard part chemistry to combat seafood fraud, quantify past food webs, as well as to reconcile growth, movement, thermal, metabolic, stress and reproductive life-histories provide opportunities to examine how harvesting and global change impact fish health and fisheries productivity. Ultimately, improved appreciation of the many practical benefits of archival tissue chemistry to fisheries and ecosystem-based management will support their increased implementation into routine monitoring.[GRAPHICS]

Reading the biomineralized book of life: expanding otolith biogeochemical research and applications for fisheries and ecosystem-based management

AbstractChemical analysis of calcified structures continues to flourish, as analytical and technological advances enable researchers to tap into trace elements and isotopes taken up in otoliths and other archival tissues at ever greater resolution. Increasingly, these tracers are applied to refine age estimation and interpretation, and to chronicle responses to environmental stressors, linking these to ecological, physiological, and life-history processes. Here, we review emerging approaches and innovative research directions in otolith chemistry, as well as in the chemistry of other archival tissues, outlining their value for fisheries and ecosystem-based management, turning the spotlight on areas where such biomarkers can support decision making. We summarise recent milestones and the challenges that lie ahead to using otoliths and archival tissues as biomarkers, grouped into seven, rapidly expanding and application-oriented research areas that apply chemical analysis in a variety of contexts, namely: (1) supporting fish age estimation; (2) evaluating environmental stress, ecophysiology and individual performance; (3) confirming seafood provenance; (4) resolving connectivity and movement pathways; (5) characterising food webs and trophic interactions; (6) reconstructing reproductive life histories; and (7) tracing stock enhancement efforts. Emerging research directions that apply hard part chemistry to combat seafood fraud, quantify past food webs, as well as to reconcile growth, movement, thermal, metabolic, stress and reproductive life-histories provide opportunities to examine how harvesting and global change impact fish health and fisheries productivity. Ultimately, improved appreciation of the many practical benefits of archival tissue chemistry to fisheries and ecosystem-based management will support their increased implementation into routine monitoring. Graphical abstract</jats:p

Subsequent Event Risk in Individuals with Established Coronary Heart Disease:Design and Rationale of the GENIUS-CHD Consortium

BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

: Reiterating the boundary: community discourse in light of proposed technological change on Vinalhaven Island, Maine, USA

This qualitative work is a case study of Vinalhaven, a small Maine island, and its negotiation of the intersection of technology use, space, place, and identity. Using a phenomenologically informed theoretical approach coupled with a version of Foucault’s archaeology of discourse (1972, 1994) as a method of analysis, the role of place and space is explored in the context of a bounded community’s public discussion about whether or not to build a cell phone tower on the island. In opposition to the oft-cited narrative of technology-as-connective-panacea, the discourse of the community surrounding the potential technology serves to complicate the community’s expression of its boundaries. If anything, the potential introduction of a new form of connectivity for the island community prompts a reaffirmation and re-articulation of the community’s boundaries, its sense of self, and its experience of isolation. The case study offers insight into approaches to the introduction of connective technologies and infrastructures in island communities, thus extending both place-based theories of technology and the depth of island studies

An Island Place: A Limited Archaeology of Technology Use Discourse

Vinalhaven, Maine is a bucolic island community, a jewel of Penobscot Bay in central Maine. Gleaming waters and bobbing fishing boats greet the many visitors that flock to the island during Maine’s summers. During the off season, Vinalhaven has 1,200 inhabitants, while its ranks swell to roughly 5,000 at the peak of the summer tourist season. For a few months during the summer, locals and visitors alike live side-by-side in the community, paradoxically creating both a place of heightened insularity and a place of continual boundary permeations. As such, its public discourse fashions a community that is both fixed and in flux. This dissertation explores the intersections of technology, space and place in Vinalhaven. It examines the utilization of technology and the ways that people talk (and do not talk) about technologies that shape experiences. The purpose of this exploration is to better understand the articulation of place in light of the tumultuous vicissitudes of technology. While one school of thought argues that as connectivity increases, the perceived differences between places begins to fade, other studies argue that increased connectivity results in the amplification of place specificity. And yet, still other scholars argue that the boundaries themselves are key elements of community identity (Douglas, 1966). This study explores a bounded community’s identity in relation to technologies given a population that is both fluid and fixed. To undertake this analysis I proceed in five chapters. Chapter one provides an introduction to community of Vinalhaven and provides the theoretical foundations of my work. Chapter two offers insights into the history of land use management in the state of Maine and on Vinalhaven, offering a context for further analysis. Chapter three explores discourse surrounding the potential construction of a cell phone tower. Chapter four offers examines the community’s relationship with transportation technologies and the parallel discursive patterns that indicate that whether the technology in question is physical or non-physical, the primary concern is the movement of bodies. Chapter five offers a few concluding thoughts on the nexus of place, technology, and identity, as well as identifying opportunities for additional scholarship