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There is a significant overlap between HIV infection and substance use disorders. Dopamine (DA) is the most abundantly upregulated neurotransmitter in Methamphetamine abuse, with receptors (DRD1-5) that are expressed by neurons as well as by a large diversity of cell types, including innate immune cells that are targets of HIV infection, making them responsive to the hyperdopaminergic environment that is characteristic of stimulant drugs. Therefore, the presence of high levels of dopamine may affect the pathogenesis of HIV, particularly in the brain. The stimulation of HIV-latently infected U1promonocyteswith DA significantly increased viral p24 levels in the supernatant at 24 hrs, suggesting effects on activation and replication.Using selective agonists to different DRDs, we found that DRD1 played a major role in activating viral transcription, followed by DRD4, which increased p24 with a slower kinetic. Transcriptome and systems biology analyses led to the identification of a cluster of genes responsive to DA, where S100A8 and S100A9 were most significantly correlated with the early increase of p24 levels following DA stimulation. Conversely, DA increased the expression of these genes’ transcripts at the protein level, respectively MRP8 and MRP14, which form a complex also known as Calprotectin. Interestingly, MRP8/14 was able to stimulate HIV transcription in latent U1 cells, and this occurred via binding to the receptor for advanced glycosylation end-product (RAGE). Using selective agonists, both DRD1 and DRD4 increased MRP8/14 on the surface and in the cytoplasm, as well as secreted in the supernatants. On the other hand, while DRD1/5 did not affect the expression of RAGE, DRD4 stimulation caused its downregulation, offering a mechanistic for the delayed effect via DRD4 on p24 increase. To cross-validate MRP8/14 as a DA signature with biomarker value, we tested its expression in HIV+ Meth users’ brains and peripheral cells. MRP8/14+ cells were more frequently identified in mesolimbic areas such as basal ganglia of HIV+ Meth+ cases compared to HIV+ non-Meth users or to controls. Likewise, MRP8/14+ CD11b+ monocytes were more frequent in HIV+ Meth users, particularly in participants with detectable viral load in the CSF. Overall, our results suggest that the MRP8 and MRP14 complex may serve as a signature to distinguish subjects using addictive substances in the context of HIV, and that this may playa role in aggravating HIV pathology by promoting viral replication in people with HIV who use Meth.&nbsp

Objectives: As the population ages and implantation criteria are relaxed, more patients with complex comorbidities are becoming eligible for cochlear implantation (CI). These patients have higher risks associated with general anesthesia. This systematic review assesses outcomes and complications following CI under local anesthetic to examine utility for patients deemed not suitable or at high risk for general anesthesia. Methods: A systematic review and meta-analysis performed according to the 2020 PRISMA guidelines. Databases searched were MEDLINE, PubMed, EMBASE, CINAHL, Web of Science Core Collection, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. There were no limitations on year of publication or language. Results: Then, 132 unique were identified. After screening abstracts and full texts for eligibility criteria a total of 18 articles were included. In the nine studies where audiological data were reported, all patients demonstrated improvement in audiological outcomes following implantation under local anesthetic (LA). Only minor complications of transient vertigo, wound infection, facial nerve paralysis, confusion, and tinnitus were reported but all were transient. Meta-analysis showed surgical time was significantly shorter under LA. Conclusions: CI under LA is safe for patients with comorbidities which preclude them from general anesthesia, with minimal complications and an improved cost-effectiveness profile. However, larger scale, robust trials are required to assess this further.

OBJECTIVES: To report changes in practice brought about by COVID-19 and the implementation of new guidelines, and to explore factors relating to unscheduled re-presentations for patients discharged from the emergency department (ED). DESIGN: Prospective multicentre national audit over 12 weeks from 6th April 2020. SETTING: UK secondary care ENT departments. PARTICIPANTS: Adult patients with acute epistaxis. MAIN OUTCOME MEASURES: Re-presentation within 10 days for patients discharged from the ED. RESULTS: Eighty three centres from all four UK nations submitted 2631 valid cases. The majority of cases were ED referrals (89.7%, n = 2358/2631). 54.6% were discharged from the ED following ENT review (n = 1267/2322), of whom 19.5% re-presented within 10 days (n = 245/1259) and 6.8% were ultimately admitted (n = 86/1259). 46.7% of patients had a non-dissolvable pack inserted by ED prior to referral to ENT (n = 1099/2355). The discharge rates for ED patients and their subsequent re-presentation rates were as follows: non-dissolvable packs, 29.5% discharged (n = 332/1125), 18.2% re-presented (n = 60/330); dissolvable products, 71.1% discharged (n = 488/686), 21.8% re-presented (n = 106/486); cautery only, 89.2% discharged (n = 247/277), 20.0% re-presented (n = 49/245); and no intranasal intervention, 85.5% discharged (n = 200/234), 15.2% re-presented (n = 30/198). Univariable logistic regression showed that not being packed by ED, antiplatelet medications, failed cautery and recent epistaxis treatment were significant predictors of re-presentation within 10 days. CONCLUSIONS: Management of acute epistaxis was notably affected during the initial peak of the pandemic, with a shift towards reduced admissions. This national audit highlights that many patients who may previously have been admitted to hospital may be safely discharged from the ED following acute epistaxis.

This project explores and tests how the cultural heritage values of buildings and structures can be incorporated into an ecosystem services framework, through considering them as both an integral part of their associated historic spaces and of their wider landscape settings. The project applies a methodology that identifies the ecosystem service outcomes from buildings, expressed in terms of flows of benefits over time, and attributes monetary values that are compatible with the ecosystem services approach. The method focuses on identifying and measuring the flow of ecosystem services over time arising from the current level of ‘natural capital’ (the stock), in a site or a defined area. The project team have developed and applied an environmental value accounting model that identifies the benefits and attributes the values associated with historic buildings and structures. The model is based on a ‘return-on-investment’ accounting framework that integrates historic function, character and significance of buildings (or other structures) with a range of agricultural, environmental, economic, and social functions to analyse the range of values generated. The cultural heritage (historic) value of buildings in the case study areas is assessed through the integration of three scored characteristics (time depth, inter-relationships, legibility). This desk-based identification of the extent to which the historic buildings and structures in an area contribute ecosystem services is aimed at enhancing understanding of the value of the annual flow of benefits generated by cultural heritage.

This project is one of a series of pilot projects that seek to address the need for the heritage sector to better engage with the ecosystem services approach to assess the benefits that cultural heritage can provide to people’s health, wellbeing and prosperity. Understanding and capturing variability in the landscape context of historic linear features is the focus of this project. The key objectives for the project are: Develop a research methodology for recording the public and environmental benefits (goods and services) arising from the historic environment, and specifically flowing from linear features in the Lower Severn Vale. Identify those benefits in a way that is compatible with ‘ecosystem services’ and ‘natural capital’ approaches. Attribute value (economic and non-economic) to those benefits (services). Identify other values that fall outside the ecosystem services framework that can be ascribed to heritage assets. Provide the heritage and natural environment sectors with case study examples, tested at different scales of application, of how this might work for different environmental contexts. The project builds on existing techniques for valuing the benefits of market and non-market goods and services and has tested the scope for integrating a range of digital and GIS mapping data into the accounting methodology. The project was carried out in the Lower Severn Vale (LSV), which is situated within the Severn and Avon Vales National Character Area (NCA) and flanked by the Cotswolds and the Forest of Dean NCAs, offering a range of settings to explore the variability of historic linear features and the benefits they offer. Linear features comprise field boundaries, routeways, and other forms of physical structure such as flood protection barriers and drainage features around the River Severn (dykes, embankments, ditches, channels, etc.). The three case studies, which were chosen in consultation with Historic England, were selected in order to explore variations within areas marked by similar characteristics bordering both sides of the Severn.

This project explores and tests how the cultural heritage values of buildings and structures can be incorporated into an ecosystem services framework, through considering them as both an integral part of their associated historic spaces and of their wider landscape settings. The project applies a methodology that identifies the ecosystem service outcomes from buildings, expressed in terms of flows of benefits over time, and attributes monetary values that are compatible with the ecosystem services approach. The method focuses on identifying and measuring the flow of ecosystem services over time arising from the current level of 'natural capital' (the stock), in a site or a defined area. The project team have developed and applied an environmental value accounting model that identifies the benefits and attributes the values associated with historic buildings and structures. The model is based on a 'return-on-investment' accounting framework that integrates historic function, character and significance of buildings (or other structures) with a range of agricultural, environmental, economic, and social functions to analyse the range of values generated. The cultural heritage (historic) value of buildings in the case study areas is assessed through the integration of three scored characteristics (time depth, inter-relationships, legibility). This desk-based identification of the extent to which the historic buildings and structures in an area contribute ecosystem services is aimed at enhancing understanding of the value of the annual flow of benefits generated by cultural heritage. This project explores and tests how the cultural heritage values of buildings and structures can be incorporated into an ecosystem services framework, through considering them as both an integral part of their associated historic spaces and of their wider landscape settings. The project applies a methodology that identifies the ecosystem service outcomes from buildings, expressed in terms of flows of benefits over time, and attributes monetary values that are compatible with the ecosystem services approach. The method focuses on identifying and measuring the flow of ecosystem services over time arising from the current level of 'natural capital' (the stock), in a site or a defined area.

The changing climate of Wales is likely to have significant direct (e.g. changing land cover) and indirect (e.g. by influencing land use decisions) impacts on landscape character, quality and local distinctiveness. Flooding and drought events, more frequent extreme weather, coastal erosion, wildfires, diseases affecting tree cover and changing land cover, habitats and species ranges are examples of how the landscape may change to a greater or lesser degree, in the short or long term.\ud \ud Landscape character can provide an important communication tool to raise awareness and understanding of the risks and opportunities of climate change because people relate to landscapes as places to live, work and enjoy. It is therefore opportune to bring together information on the impacts from a changing climate and apply them to a landscape perspective.\ud \ud This project is the first step in starting to identify and communicate the direct and indirect impacts of projected climate changes for Wales in 2050 on landscape character and qualities and what that might look like in the landscape we recognise today. This project identifies the impacts of climate change on broad landscape types using the LANDMAP Visual & Sensory spatial dataset. It provides maps that identify the spatial distribution of the broad landscape types supported by key statistics, and offers a series of written narratives of potential change for each landscape type.

Dry stone walls are an integral part of the landscape and cultural heritage of the PDNP and other upland areas of England, marking routeways, territorial, occupancy and tenurial boundaries, separating rough grazing from meadows, pastures and arable land and enabling the management and movement of people and livestock. As the stilldominant form of enclosure in the PDNP dry stone walls are part of the 'scenery' appreciated by residents and visitors, and also providing wildlife habitats and corridors. A report on landscape change in the National Parks of England and Wales, published in 1991 by the Countryside Commission, estimated that in the PDNP there were 8,756 kilometres (km) of dry stone walls, 1,710 km of hedges and 472 km of fences. Although the PDNP has experienced greater loss of field boundaries than any other National Park, it still has the third highest density of dry stone walls in any of the National Parks - at an average of 7.6 km2. The approach to valuing the benefit streams flowing from dry stone walls is based on a simple ROI model using financial approximations ('proxy measures') to estimate values of the benefit flows. Within the model the functions of dry stone walls were allocated to the four main ecosystem services categories (provisioning, supporting, regulating, cultural). Annual costs of wall restoration and maintenance, and annual benefits produced were modelled over a 50-year time horizon. Annual costs and benefits were discounted back to present value (using a 3.5% discount rate) and summed to provide total present values for costs and benefits of dry stone walls over the period.

This report presents results from a return-on-investment (ROI) model developed to explore ways in which historic environment values can be incorporated into the four categories of ecosystem services. The model is based on identifying and monetising the\ud benefit flows from ecosystem services provided by dry stone walls in the Peak District National Park (PDNP). The overall project aims involved: development of a methodology for recording the public and environmental benefits (goods and services)flowing from dry stone walls in the PDNP; identification of those benefits in a way that is compatible with the language associated with ‘ecosystem services’ and ‘natural capital’; attribution of value (economic and non- economic) to those benefits (services); and, to recommend other heritage assets for which this approach would be suitable.

The PEGASUS project aimed to identify how to promote enhanced delivery of environmental and social benefits from farming and forestry, across the EU. After three years of investigation and analysis it has distilled a number of lessons for both policy and practice. Policy recommendations are focused upon national and European policy makers and in particular, consider ways to improve the environmental and social outcomes of the new CAP, beyond 2020. These are the subject of another deliverable from the project (D5.4). This deliverable, D5.3, provides a compendium of lessons for practitioners who are interested in seeking to enhance multiple benefits from farming and forestry, within a territory or along a supply chain. Learning from 34 case study examples around Europe (for a full list, see Table 4 in D5.1), and from validation of the case study findings with multiple stakeholders in national and EU-wide seminars and workshops, this report draws together a set of common principles and supporting methods to help local actors. It summarises the wide range of lessons from the project concerning transferable methods for the successful delivery of ‘Public and Ecosystem Goods And Services from farming and forestry; Unlocking Synergies’. It aims to provide a relatively comprehensive analysis of good practice for successful initiatives. Because it is derived from a very broad range of situations and contrasting types of experience, these lessons should be transferable to a wide variety of contexts in Europe.

This book presents an overview of CCRI's research activities during 2017.

The Countryside and Community Research Institute at the University of Gloucestershire was contracted by North Devon Plus in Autumn 2014 to undertake an update to the 2004 ‘State of Farming’ on Exmoor report. The study was to identify the state of farming in Exmoor - an upland National Park and distinctive, protected landscape - and consider prospects for the future, as well as making recommendations for policy. The study team was guided by a steering group drawn from Exmoor Hill Farming Network (EHFN), Exmoor National Park Authority (ENPA) and North Devon Plus. Study funding came from ENPA and the Rural Development Programme for England (Defra).