Regional coastal flood risk assessment for a tidally dominant, natural coastal setting: North Norfolk, southern North Sea

A Coastal Risk Assessment Framework (CRAF) provides two levels of coastal risk and vulnerability assessment, by combining information on the spatially variable hazard and exposure. In Phase 1, areas of greatest risk or `hotspots' are identified. In Phase 2, these hotspots are then analysed in greater detail to identify both direct and indirect extreme event impacts. This approach was applied to the barrier coastline of North Norfolk, eastern England. The CRAF identified high risk coastal hotspots on the basis of both hazard impacts (swash regime (tide + surge + wave runup) and overwash/terrestrial inundation regimes) from a 1 in 115 year return period storm and a range of land use, infrastructure, economic and social vulnerability indicators. Hazard extents and hazard severity, in some locations modified by the presence of intertidal saltmarsh, were calculated for 45, 1-2 km wide sections along the topographically complex coast. When combined with five exposure indicators, eight hotspots were identified along the 45 km long frontage. In a 2nd phase, two of these hotspots, one a chain of small villages (Brancaster/Brancaster Staithe/Burnham Deepdale) and one a small town (Wells-next-the-Sea), were compared in more detail using a suite of coastal inundation and impact assessment models to determine both direct and indirect impacts. Hazards at this higher resolution were calculated using the 1D process-based XBeach model and the 2D LISFLOOD inundation model. Vulnerability to the hazards was calculated using the INDRA (Integrated Disruption Assessment) model with comparison of the two hotspots through the use of a Multi Criteria Analysis (MCA). The selection of hazard hotspots and comparison of hotspots using these techniques allows areas at greatest risk to be identified, of vital importance for coastal management and resource allocation.This work was supported by the European Community’s 7th Framework Programme through the grant to RISC-KIT (“Resilience-increasing Strategies for Coasts Toolkit”), contract no. 603458, and by contributions by the partner institutes and a grant from The Isaac Newton Trust, Trinity College, Cambridge

Coastal ecosystems: A critical element of risk reduction

The conservation of coastal ecosystems can provide considerable coastal protection benefits, but this role has not been sufficiently accounted for in coastal planning and engineering. Substantial evidence now exists showing how, and under what conditions, ecosystems can play a valuable function in wave and storm surge attenuation, erosion reduction, and in the longer term maintenance of the coastal profile. Both through their capacity for self repair and recovery, and through the often considerable cobenefits they provide, ecosystems can offer notable advantages over traditional engineering approaches in some settings. They can also be combined in "hybrid" engineering designs. We make 10 recommendations to encourage the utilization of existing knowledge and to improve the incorporation of ecosystems into policy, planning and funding for coastal hazard risk reduction

Effect of roflumilast on inflammatory cells in the lungs of cigarette smoke-exposed mice

<p>Abstract</p> <p>Background</p> <p>We reported that roflumilast, a phosphodiesterase 4 inhibitor, given orally at 5 mg/kg to mice prevented the development of emphysema in a chronic model of cigarette smoke exposure, while at 1 mg/kg was ineffective. Here we investigated the effects of roflumilast on the volume density (V_V) of the inflammatory cells present in the lungs after chronic cigarette smoke exposure.</p> <p>Methods</p> <p>Slides were obtained from blocks of the previous study and V_Vwas assessed immunohistochemically and by point counting using a grid with 48 points, a 20× objective and a computer screen for a final magnification of 580×. Neutrophils were marked with myeloperoxidase antibody, macrophages with Mac-3, dendritic cells with fascin, B-lymphocytes with B220, CD4+ T-cells with CD4+ antibody, and CD8+T-cells with CD8-α. The significance of the differences was calculated using one-way analysis of variance.</p> <p>Results</p> <p>Chronic smoke exposure increased neutrophil V_Vby 97%, macrophage by 107%, dendritic cell by 217%, B-lymphocyte by 436%, CD4+ by 524%, and CD8+ by 417%. The higher dose of roflumilast prevented the increase in neutrophil V_Vby 78%, macrophage by 82%, dendritic cell by 48%, B-lymphocyte by 100%, CD4+ by 98% and CD8+ V_Vby 88%. The lower dose of roflumilast did not prevent the increase in neutrophil, macrophage and B-cell V_Vbut prevented dendritic cells by 42%, CD4+ by 55%, and CD8+ by 91%.</p> <p>Conclusion</p> <p>These results indicate (<it>i</it>) chronic exposure to cigarette smoke in mice results in a significant recruitment into the lung of inflammatory cells of both the innate and adaptive immune system; (<it>ii</it>) roflumilast at the higher dose exerts a protective effect against the recruitment of all these cells and at the lower dose against the recruitment of dendritic cells and T-lymphocytes; (<it>iii</it>) these findings underline the role of innate immunity in the development of pulmonary emphysema and (<it>iiii</it>) support previous results indicating that the inflammatory cells of the adaptive immune system do not play a central role in the development of cigarette smoke induced emphysema in mice.</p

Global value chain configuration: A review and research agenda

This paper reviews the literature on global value chain configuration, providing an overview of this topic. Specifically, we review the literature focusing on the concept of the global value chain and its activities, the decisions involved in its configuration, such as location, the governance modes chosen and the different ways of coordinating them. We also examine the outcomes of a global value chain configuration in terms of performance and upgrading. Our aim is to review the state of the art of these issues, identify research gaps and suggest new lines for future research that would advance our understanding of how firms are implementing new ways of organizing and managing activities on a global scale

Perceptions of clinicians and staff about the use of digital technology in primary care: qualitative interviews prior to implementation of a computer-facilitated 5As intervention

BACKGROUND: Digital health interventions using hybrid delivery models may offer efficient alternatives to traditional behavioral counseling by addressing obstacles of time, resources, and knowledge. Using a computer-facilitated 5As (ask, advise, assess, assist, arrange) model as an example (CF5As), we aimed to identify factors from the perspectives of primary care providers and clinical staff that were likely to influence introduction of digital technology and a CF5As smoking cessation counseling intervention. In the CF5As model, patients self-administer a tablet intervention that provides 5As smoking cessation counseling, produces patient and provider handouts recommending next steps, and is followed by a patient-provider encounter to reinforce key cessation messages, provide assistance, and arrange follow-up. METHODS: Semi-structured in-person interviews of administrative and clinical staff and primary care providers from three primary care clinics. RESULTS: Thirty-five interviews were completed (12 administrative staff, ten clinical staff, and 13 primary care providers). Twelve were from an academic internal medicine practice, 12 from a public hospital academic general medicine clinic, and 11 from a public hospital HIV clinic. Most were women (91 %); mean age (SD) was 42 years (11.1). Perceived usefulness of the CF5As focused on its relevance for various health behavior counseling purposes, potential gains in counseling efficiency, confidentiality of data collection, occupying patients while waiting, and serving as a cue to action. Perceived ease of use was viewed to depend on the ability to accommodate: clinic workflow; heavy patient volumes; and patient characterisitics, e.g., low literacy. Social norms potentially affecting implementation included beliefs in the promise/burden of technology, priority of smoking cessation counseling relative to other patient needs, and perception of CF5As as just “one more thing to do” in an overburdened system. The most frequently cited facilitating conditions were staffing levels and smoking cessation resources and training; the most cited hindering factors were visit time constraints and patients’ complex health care needs. CONCLUSIONS: Integrating CF5As and other technology-enhanced behavioral counseling interventions in primary care requires flexibility to accommodate work flow and perceptions of overload in dynamic environments. Identifying factors that promote and hinder CF5As adoption could inform implementation of other CF behavioral health interventions in primary care

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation