Why are we here? A study of patient actions prior to emergency hospital admission

Introduction: Emergency department (ED) attendances and subsequent hospital admissions are rising in the United Kingdom. The reasons for this are unclear but may relate to recent changes in primary care and public perception. The actions taken by patients or their relatives before emergency hospital admission, the reasons for these actions and their outcome were determined. Methods: Adult patients admitted to an inner city teaching hospital with a medical or surgical illness were interviewed using a semistructured questionnaire. Data were collected and analyzed regarding the actions taken before arrival at hospital, the reasons for taking these actions, their outcome and future intentions. 200 patients were interviewed. Results: Direct attendance at the ED was more common when help was sought by bystanders or persons known only slightly to the patient (p = 0.03). 57 patients (28.5%) attended the ED directly, 45 of whom dialled 999 for an emergency ambulance. Most patients who attended the ED directly did so as a result of the perceived severity or urgency of their condition and there was incomplete awareness of the out-of-hours GP service. Conclusion: The majority of adult patients who are admitted to hospital with an acute illness seek professional help from primary care in the first instance. Those who attend the ED generally perceive their problem as more urgent or severe, or have an ambulance called on their behalf. The shift towards ED care appears partly driven by changes in general practice and unfamiliarity with the new arrangements for out-of-hours primary care provision

Global inequities and political borders challenge nature conservation under climate change

Underlying sociopolitical factors have emerged as important determinants of wildlife population trends and the effectiveness of conservation action. Despite mounting research into the impacts of climate change on nature, there has been little consideration of the human context in which these impacts occur, particularly at the global scale. We investigate this in two ways. First, by modeling the climatic niches of terrestrial mammals and birds globally, we show that projected species loss under climate change is greatest in countries with weaker governance and lower Gross Domestic Product, with loss of mammal species projected to be greater in countries with lower CO2 emissions. Therefore, climate change impacts on species may be disproportionately significant in countries with lower capacity for effective conservation and lower greenhouse gas emissions, raising important questions of international justice. Second, we consider the redistribution of species in the context of political boundaries since the global importance of transboundary conservation under climate change is poorly understood. Under a high-emissions scenario, we find that 35% of mammals and 29% of birds are projected to have over half of their 2070 climatic niche in countries in which they are not currently found. We map these transboundary range shifts globally, identifying borders across which international coordination might most benefit conservation and where physical border barriers, such as walls and fences, may be an overlooked obstacle to climate adaptation. Our work highlights the importance of sociopolitical context and the utility of a supranational perspective for 21st century nature conservation

Inhibition of vascular smooth muscle cell calcification by ATP analogues

Arterial medial calcification (AMC) has been associated with phenotypic changes in vascular smooth muscle cells (VSMCs) that reportedly makes them more osteoblast-like. Previous work has shown that ATP/UTP can inhibit AMC directly via P2 receptors and indirectly by NPP1-mediated hydrolysis to produce the mineralisation inhibitor, pyrophosphate (PPi). This study investigated the role of P2X receptors in the inhibitory effects of extracellular nucleotides on VSMC calcification. We found that Bz-ATP, α,β-meATP and β,γ-meATP, inhibited calcification by up to 100%. Culture in a high phosphate medium (2mM) was associated with increased VSMC death and apoptosis; treatment with Bz-ATP, α,β-meATP and β,γ-meATP reduced apoptosis to levels seen in non-calcifying cells. Calcification was also associated with alterations in the protein levels of VSMC (e.g. SM22α, SMA) and osteoblast-associated (e.g. Runx2, osteopontin) markers; Bz-ATP, α,β-meATP and β,γ-meATP attenuated these changes in protein expression. Long-term culture with Bz-ATP, α,β-meATP and β,γ-meATP resulted in lower extracellular ATP levels and an increased rate of ATP breakdown. P2X receptor antagonists failed to prevent the inhibitory effects of these analogues suggesting that they act via P2X receptor-independent mechanisms. In agreement, the breakdown products of α,β-meATP and β,γ-meATP (α,β-meADP and methylene diphosphonate, respectively) also dose dependently inhibited VSMC calcification. Furthermore, the actions of Bz-ATP, α,β-meATP and β,γ-meATP were unchanged in VSMCs isolated from NPP1 knockout mice, suggesting that the functional effects of these compounds do not involve NPP1-mediated generation of PPi. Together, these results indicate that the inhibitory effects of ATP analogues on VSMC calcification and apoptosis in vitro may be mediated, at least in part, by mechanisms that are independent of purinergic signalling and PPi

Evaluating the suitability of close-kin mark-recapture as a demographic modelling tool for a critically endangered elasmobranch population

Funding Information: We are grateful to the various stakeholders involved in the Celtic Sea blue skate monitoring programme, in particular to the crew aboard the FV Govenek of Ladram. We thank Martina Kopp for her assistance in the laboratory, Andrzej Kilian and the Diversity Arrays Technology team (DArT Pty. Ltd., Canberra, Australia) for performing the genotyping work, and Daniel Ruzzante, Eric Anderson, Mark Bravington, and Robin Waples for their inputs during the early stages of the project at a CKMR workshop at Dalhousie University, Halifax, Canada. MF and CSJ received funding from the MASTS (The Marine Alliance for Science and Technology for Scotland), and their support is gratefully acknowledged. MASTS is funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions. Our thanks also go to Professor Francis Neat for his expertise and advice on Scottish blue skates, and to Samuel Iglésias and Thomas Barreau for sharing valuable insights from their studies on Celtic Sea blue skate.Peer reviewe

A systematic review and meta-analysis of randomised controlled trials on surgical treatments for ingrown toenails part I : recurrence and relief of symptoms

Background Ingrown toenails are a common nail pathology. When conservative treatments are ineffective, a surgical approach is often utilised. Despite recent narrative reviews, there is a need for an up-to-date and rigorous systematic review of surgical methods for treating ingrown toenails. Methods Five databases (MEDLINE, Embase, CINAHL, Web of Science and CENTRAL) and two registers (Clinicaltrials.gov and ISRCTN) were searched to January 2022 for randomised trials evaluating the effects of a surgical intervention(s) for ingrown toenails with a follow-up of at least 1 month. Two independent reviewers screened records, extracted data, assessed risk of bias and certainty of evidence. Results Of 3,928 records identified, 36 (3,756 participants; 62.7% males) surgical interventions were included in the systematic review and 31 studies in the meta-analysis. There was very low quality evidence that using phenol with nail avulsion vs nail avulsion without phenol reduces the risk of recurrence (risk ratio [RR] 0.13 [95% CI 0.06 to 0.27], p < 0.001). No favourable effect was observed between chemical or surgical vs conservative management (0.55 [0.19 to 1.61], p = 0.280; 0.72 [0.33 to 1.56], p = 0.410), chemical or surgical vs other (e.g., CO2 laser, electrocautery) (1.61 [0.88 to 2.95], p = 0.120; 0.58 [0.25 to 1.37], p = 0.220), chemical vs surgical (0.75 [0.46 to 1.21], p = 0.230), surgical vs surgical (0.42 [0.21 to 0.85]), chemical vs chemical (0.19 [0.01 to 3.80], p = 0.280), surgical vs surgical + chemical (3.68 [0.20 to 67.35], p = 0.380), chemical vs surgical + chemical (1.92 [0.06 to 62.30], p = 0.710), local anaesthetic vs local anaesthetic + adrenaline (1.03 [0.22 to 4.86], p = 0.970), chemical timings 30 s vs 60 s (2.00 [0.19 to 21.41]) or antibiotics vs no antibiotics (0.54 [0.12 to 2.52], p = 0.430). Central toenail resection was the only procedure to significantly relieve symptoms (p = 0.001) but data were only available up to 8 weeks post-surgery. Conclusion Despite the high number of publications, the quality of research was poor and the conclusions that can be inferred from existing trials is limited. Phenolisation of the nail matrix appears to reduce the risk of recurrence following nail ablation, and with less certainty 1 min appears to be the optimum time for application. Despite this being a widely performed procedure there remains a lack of good quality evidence to guide practice

Carbon exchange between a shelf sea and the ocean: The Hebrides Shelf, west of Scotland

Global mass balance calculations indicate the majority of particulate organic carbon (POC) exported from shelf seas is transferred via downslope exchange processes. Here we demonstrate the downslope flux of POC from the Hebrides Shelf is approximately 3-to-5-fold larger per unit length/area than the global mean. To reach this conclusion we quantified the offshore transport of particulate and dissolved carbon fractions via the “Ekman Drain”, a strong downwelling feature of the NW European Shelf circulation, and subsequently compared these fluxes to simultaneous regional air-sea CO2 fluxes and on-shore wind-driven Ekman fluxes to constrain the carbon dynamics of this shelf. Along the shelf break we estimate a mean offshelf total carbon (dissolved + particulate) flux of 4.2 tonnes C m−1 d−1 compared to an onshelf flux of 4.5 tonnes C m−1 d−1. Organic carbon represented 3.3% of the onshelf carbon flux but 6.4% of the offshelf flux indicating net organic carbon export. Dissolved organic carbon represented 95% and POC 5% of the exported organic carbon pool. When scaled along the shelf break the total offshelf POC flux (0.007 Tg C d−1) was found to be three times larger than the regional air-sea CO2 ingassing flux (0.0021 Tg C d−1), an order of magnitude larger than the particulate inorganic carbon flux (0.0003 Tg C d−1) but far smaller than the DIC (2.03 Tg C d−1) or DOC (0.13 Tg C d−1) fluxes. Significant spatial heterogeneity in the Ekman drain transport confirms that offshelf carbon fluxes via this mechanism are also spatially heterogeneous. This article is protected by copyright. All rights reserved

The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis

Summary: Expression of the initiator methionine tRNA (tRNAi Met) is deregulated in cancer. Despite this fact, it is not currently known how tRNAi Met expression levels influence tumor progression. We have found that tRNAi Met expression is increased in carcinoma-associated fibroblasts, implicating deregulated expression of tRNAi Met in the tumor stroma as a possible contributor to tumor progression. To investigate how elevated stromal tRNAi Met contributes to tumor progression, we generated a mouse expressing additional copies of the tRNAi Met gene (2+tRNAi Met mouse). Growth and vascularization of subcutaneous tumor allografts was enhanced in 2+tRNAi Met mice compared with wild-type littermate controls. Extracellular matrix (ECM) deposited by fibroblasts from 2+tRNAi Met mice supported enhanced endothelial cell and fibroblast migration. SILAC mass spectrometry indicated that elevated expression of tRNAi Met significantly increased synthesis and secretion of certain types of collagen, in particular type II collagen. Suppression of type II collagen opposed the ability of tRNAi Metoverexpressing fibroblasts to deposit pro-migratory ECM. We used the prolyl hydroxylase inhibitor ethyl- 3,4-dihydroxybenzoate (DHB) to determine whether collagen synthesis contributes to the tRNAi Met-driven pro-tumorigenic stroma in vivo. DHB had no effect on the growth of syngeneic allografts in wild-type mice but opposed the ability of 2+tRNAi Met mice to support increased angiogenesis and tumor growth. Finally, collagen II expression predicts poor prognosis in high-grade serous ovarian carcinoma. Taken together, these data indicate that increased tRNAi Met levels contribute to tumor progression by enhancing the ability of stromal fibroblasts to synthesize and secrete a type II collagen-rich ECM that supports endothelial cell migration and angiogenesis

IL-10 differentially controls the infiltration of inflammatory macrophages and antigen-presenting cells during inflammation

The inflammatory activation and recruitment of defined myeloid populations is essential for controlling the bridge between innate and adaptive immunity and shaping the immune response to microbial challenge. However, these cells exhibit significant functional heterogeneity and the inflammatory signals that differentially influence their effector characteristics are poorly characterized. In this study, we defined the phenotype of discrete subsets of effective antigen-presenting cells (APCs) in the peritoneal cavity during peritonitis. When the functional properties of these cells were compared to inflammatory monocyte-derived macrophages we noted differential responses to the immune-modulatory cytokine IL-10. In contrast to the suppressive actions of IL-10 on inflammatory macrophages, the recruitment of APCs was relatively refractory and we found no evidence for selective inhibition of APC differentiation. This differential response of myeloid cell subsets to IL-10 may thus have limited impact on development of potentially tissue-damaging adaptive immune responses, whilst restricting the magnitude of the inflammatory response. These findings may have clinical relevance in the context of peritoneal dialysis patients, where recurrent infections are associated with immune-mediated membrane dysfunction, treatment failure and increased morbidity

“We are still quite patchy about what we know” International migration and the challenges of definition, categorisation and measurement on local service provision

International migration has a consistently high profile within national and international politics with increased focus on measurement and quantification of migrant numbers, impact on services and contribution to local, regional and national economies. However, the absence of consistency within definitions, categorisations and measurement of international migration and migrant populations create challenges and barriers to both understanding the needs of migrant communities but also the provision of adequate services within specific geographical areas. This paper will present findings from a project designed to map the impact of migration on a settled community within a Local Authority (LA) in the North East of England. As the project encountered routine inconsistencies around definitions, categorisations and measurement of migration within the LA area, this paper demonstrates the complexity of trying to ‘measure’ migration on the ground and while consistency in measurement is key to accurate data, we conclude with an ethical question about the rationale for collecting data on migrant populations