The Importance Of Taper In Luminal Arterial Geometry: An In Vitro And In Vivo Analysis

Arterial diseases such as atherosclerosis and aneurysms occur in human arteries, and may be induced by local differences in hemodynamic or elastic forces. Both of these forces are tied to the geometry of the lumen. The goal of this study was to measure luminal cross-sectional area variation (area taper) in Y-bifurcations of muscular arteries (porcine renals) and elastic arteries (human aorto-iliac), and compare these bifurcations with data obtained previously on muscular human cerebral bifurcations. Flow accelerates as the arteries taper and decelerates as they flare. Separation zones develop with flaring.;The arteries were pressure-fixed, frozen and sliced at 10-40{dollar}\mu{dollar}m. Luminal area was measured digitally from the block face (this removed histological artifacts). Area taper, defined as the change in luminal area per unit length of artery, was calculated and found to be {dollar}-{dollar}1.4mm ({dollar}\pm{dollar} 0.2 mm S.E.M.) (n = 13) in the parent branch of the renal arterial bifurcations and {dollar}-{dollar}1.5mm {dollar}\pm{dollar} 0.3mm (n = 6) in the parent branch of human cerebral bifurcations. Negative area taper corresponded to an expansion. The maximum cross-sectional area was at the flow divider in both renal and cerebral bifurcations but not in the aorto-iliac bifurcation. The human aorto-iliac had three area tapers: {dollar}-{dollar}0.7 {dollar}\pm{dollar} 0.1mm in the pre-apical region, +2.4 {dollar}\pm{dollar} 0.7mm in the apical region and {dollar}-{dollar}1.1 {dollar}\pm{dollar} 0.3 post-apically.;In vivo geometry of the human abdominal aorta was measured from aortograms and computed topographic (CT) scans from patients with and without aneurysms. CT scans (n = 25) showed the aortic lumen to be circular. Aortograms of normal aortas (n = 8) showed diameter tapers of +0.07 {dollar}\pm{dollar} 0.02 proximal to the throat and {dollar}-{dollar}0.63 {dollar}\pm{dollar} 0.06 proximal to the flow divider. Abdominal aortic aneurysms had three diameter tapers: {dollar}-{dollar}0.6 {dollar}\pm{dollar} 0.2 proximal to the maximum aneurysm area (apex), +0.4 {dollar}\pm{dollar} 0.1 distal to the apex and {dollar}-{dollar}0.6 {dollar}\pm{dollar} 0.1 proximal to the flow divider.;The large tapers make measurements of area ratio reported previously prone to error. Since tapers were not significantly different in porcine renal and human cerebral bifurcations, hemodynamic factors seem less likely than structural factors to explain why aneurysms develop at the apex of cerebral bifurcations

Dexfenfluramine and the oestrogen-metabolizing enzyme CYP1B1 in the development of pulmonary arterial hypertension

<p>Aims: Pulmonary arterial hypertension (PAH) occurs more frequently in women than men. Oestrogen and the oestrogen-metabolising enzyme cytochrome P450 1B1 (CYP1B1) play a role in the development of PAH. Anorectic drugs such as dexfenfluramine (Dfen) have been associated with the development of PAH. Dfen mediates PAH via a serotonergic mechanism and we have shown serotonin to up-regulate expression of CYP1B1 in human pulmonary artery smooth muscle cells (PASMCs). Thus here we assess the role of CYP1B1 in the development of Dfen-induced PAH.</p> <p>Methods and results: Dfen (5 mg kg−1 day−1 PO for 28 days) increased right ventricular pressure and pulmonary vascular remodelling in female mice only. Mice dosed with Dfen showed increased whole lung expression of CYP1B1 and Dfen-induced PAH was ablated in CYP1B1−/− mice. In line with this, Dfen up-regulated expression of CYP1B1 in PASMCs from PAH patients (PAH-PASMCs) and Dfen-mediated proliferation of PAH-PASMCs was ablated by pharmacological inhibition of CYP1B1. Dfen increased expression of tryptophan hydroxylase 1 (Tph1; the rate-limiting enzyme in the synthesis of serotonin) in PAH-PASMCs and both Dfen-induced proliferation and Dfen-induced up-regulation of CYP1B1 were ablated by inhibition of Tph1. 17β-Oestradiol increased expression of both Tph1 and CYP1B1 in PAH-PASMCs, and Dfen and 17β-oestradiol had synergistic effects on proliferation of PAH-PASMCs. Finally, ovariectomy protected against Dfen-induced PAH in female mice.</p> <p>Conclusion: CYP1B1 is critical in the development of Dfen-induced PAH in mice in vivo and proliferation of PAH-PASMCs in vitro. CYP1B1 may provide a novel therapeutic target for PAH.</p&gt

hapbin: An Efficient Program for performing Haplotype-Based Scans for Positive Selection in Large Genomic Datasets

Understanding how the genome is shaped by selective processes forms an integral part of modern biology. However, as genomic datasets continue to grow larger it is becoming increasingly difficult to apply traditional statistics for detecting signatures of selection to these cohorts. There is therefore a pressing need for the development of the next generation of computational and analytical tools for detecting signatures of selection in large genomic datasets. Here, we present hapbin, an efficient multithreaded implementation of extended haplotype homzygosity-based statistics for detecting selection, which is up to 3,400 times faster than the current fastest implementations of these algorithms

More or Less of Me and You : Self-Relevance Augments the Effects of Item Probability on Stimulus Prioritization

Open access via Springer agreementPeer reviewedPublisher PD

Biodiversity 2020: climate change evaluation report

In 2011, the government published Biodiversity 2020: A strategy for England’s wildlife and ecosystem services [1]. This strategy for England builds on the 2011 Natural Environment White Paper - NEWP [2] and provides a comprehensive picture of how we are implementing our international and EU commitments. It sets out the strategic direction for biodiversity policy between 2011-2020 on land (including rivers and lakes) and at sea, and forms part of the UK’s commitments under the ‘the Aichi targets’ agreed in 2010 under the United Nations Convention of Biological Diversity’s Strategic Plan for Biodiversity 2011-2020 [3]. Defra is committed to evaluating the Biodiversity 2020 strategy and has a public commitment to assess climate change adaptation measures. This document sets out the information on assessing how action under Biodiversity 2020 has helped our wildlife and ecosystems to adapt to climate change. Biodiversity 2020 aims to halt the loss of biodiversity and restore functioning ecosystems for wildlife and for people. The outcomes and actions in Biodiversity 2020, although wider in scope, aimed to increase resilience of our wildlife and ecosystems in the face of a changing climate. In order to inform the assessment, we have defined which of the measurable outputs under Biodiversity 2020 contribute to resilience. Biodiversity 2020 included plans to develop and publish a dedicated set of indicators to assess progress towards the delivery of the strategy. The latest list (at the time of writing), published in 2017, contains 24 biodiversity indicators [4] that would help inform progress towards achieving specific outcomes, they are also highly relevant to the outputs (detailed below) that form the basis for this evaluation. The Adaptation Sub-Committee’s 2017 UK Climate Change Risk Assessment Evidence Report [5] sets out the priority climate change risks and opportunities for the UK. The ASC also produced a review of progress in the National Adaptation Programme - “Progress in preparing for climate change” [6], which highlights adaptation priorities and progress being made towards achieving them. The UK Government’s response to the ASC [7] review includes a set of recommendations, of which Recommendation 6 states that “Action should be taken to enhance the condition of priority habitats and the abundance and range of priority species”. The recommendation further iterated that “This action should maintain or extend the level of ambition that was included in Biodiversity 2020” and that “An evaluation should be undertaken of Biodiversity 2020 including the extent to which goals have been met and of the implications for resilience to climate change.” To this, end an evaluation process has been put in place to define: a. What worked and why? Which actions or activities have had the greatest benefit in terms of delivering the desired outcomes? And, conversely, what prevented progress? b. Where are the opportunities? What are the financial, political, scientific and social opportunities for furthering the desired outcomes in the future? These objectives underpin the evaluation process for actions to date, and will also inform future actions and the iteration of a new nature strategy for England

Organic Matter Preservation and Incipient Mineralization of Microtubules in 120 Ma Basaltic Glass

Hollow tubular structures in subaqueously-emplaced basaltic glass may represent trace fossils caused by microbially-mediated glass dissolution. Mineralized structures of similar morphology and spatial distribution in ancient, metamorphosed basaltic rocks have widely been interpreted as ichnofossils, possibly dating to similar to 3.5 Ga or greater. Doubts have been raised, however, regarding the biogenicity of the original hollow tubules and granules in basaltic glass. In particular, although elevated levels of biologically-important elements such as C, S, N, and P as well as organic compounds have been detected in association with these structures, a direct detection of unambiguously biogenic organic molecules has not been accomplished. In this study, we describe the direct detection of proteins associated with tubular textures in basaltic glass using synchrotron X-ray spectromicroscopy. Protein-rich organic matter is shown to be associated with the margins of hollow and partly-mineralized tubules. Furthermore, a variety of tubule-infilling secondary minerals, including Ti-rich oxide phases, were observed filling and preserving the microtextures, demonstrating a mechanism whereby cellular materials may be preserved through geologic time

The archaeological potential of Wogan Cavern (Pembroke, UK):Results of the first fieldwork season

Funding Information: Acknowledgements Many thanks are due to numerous people for their help with our work on Wogan Cavern, including (but not limited to) Jon Williams and the staff at Pembroke Castle, Sian Williams, several colleagues at Dyfed Archaeological Trust, Mark Lewis and Eloise Chapman at Tenby Museum, and Louise Mees at Cadw. We are also grateful to the reviewers for a careful reading of this article and for providing some insightful comments, and to David Lowe, whose comments and advice benefitted the final version of the Paper. The work described here and that planned for the future is funded by the Natural History Museum’s Human Origins Research Fund, the BCRA’s CSTRF scheme, and the Prehistoric Society. ELJ acknowledges the Belspo-ICHIE project for funding her contribution to this research.Peer reviewedPublisher PD

Do proxies reflect patients' health concerns about urinary incontinence and gait problems?

BACKGROUND: While falls and urinary incontinence are prevalent among older patients, who sometimes rely on proxies to provide their health information, the validity of proxy reports of concern about falls and urinary incontinence remains unknown. METHODS: Telephone interviews with 43 consecutive patients with falls or fear of falling and/or bothersome urinary incontinence and their proxies chosen by patients as most knowledgeable about their health. The questionnaire included items derived from the Medical Outcomes Study Short Form 12 (SF-12), a scale assessing concerns about urinary incontinence (UI), and a measure of fear of falling, the Falls Efficacy Scale (FES). Scores were estimated using items asking the proxy perspective (6 items from the SF-12, 10 items from a UI scale, and all 10 FES items). Proxy and patient scores were compared using intraclass correlation coefficients (ICC, one-way model). Variables associated with absolute agreement between patients and proxies were explored. RESULTS: Patients had a mean age of 81 years (range 75–93) and 67% were female while proxies had a mean age of 70 (range 42–87) and 49% were female. ICCs were 0.63 for the SF-12, 0.52 for the UI scale, and 0.29 for the FES. Proxies tended to understate patients' general health and incontinence concern, but overstate patients' concern about falling. Proxies who lived with patients and those who more often see patients more closely reflected patient FES scores compared to those who lived apart or those who saw patients less often. Internal consistency reliability of proxy responses was 0.62 for the SF-12, 0.86 for the I-QOL, and 0.93 for the FES. In addition, construct validity of the proxy FES scale was supported by greater proxy-perceived fear of falling for patients who received medical care after a fall during the past 12 months (p < .05). CONCLUSION: Caution should be exercised when using proxies as a source of information about older patients' health perceptions. Questions asking about proxies' views yield suboptimal agreement with patient responses. However, proxy scales of UI and fall concern are internally consistent and may provide valid independent information