Low level of virological failure and drug resistance among patients receiving antiretroviral treatment under programme conditions in Maputo, Mozambique

Mexico AIDS Conference 200

Organisational activity with land managers in relation to biodiversity renewal in four case study areas. A scoping study

This is the final version. Available from the Centre for Rural Policy Research, University of Exeter via the link in this recordIntroduction: This scoping study forms part of a wider examination of land manager engagement with biodiversity renewal, contributing to the Theme 3 objectives of RENEW. The purpose of this study was to identify how organisations are currently engaging with land managers in relation to biodiversity renewal across the four case study areas identified by the wider team, through the identification of existing (or recent) biodiversity renewal initiatives and biodiversity renewal-related networks of farmers in those areas. It also aimed to investigate stakeholder perceptions around levels of engagement, and the potential impacts upon land managers of the agricultural transition, as well as to monitor initial responses of organisational stakeholders to the ENABLR (Engagement in Nature and Biodiversity Land Renewal) decision-support tool currently being developed within Theme 3. These findings allow the research team to ‘map’ key areas of activity (and non-activity) in the four case study areas, while at the same time providing an extensive knowledge base around which to develop future research methods (such as interviews) and be able to interact with participants from an informed position. Findings may also assist and influence the development of the decision-support tool.Natural Environment Research Council (NERC

Bio-Inspired Multi-Layer Spiking Neural Network Extracts Discriminative Features from Speech Signals

Spiking neural networks (SNNs) enable power-efficient implementations due to their sparse, spike-based coding scheme. This paper develops a bio-inspired SNN that uses unsupervised learning to extract discriminative features from speech signals, which can subsequently be used in a classifier. The architecture consists of a spiking convolutional/pooling layer followed by a fully connected spiking layer for feature discovery. The convolutional layer of leaky, integrate-and-fire (LIF) neurons represents primary acoustic features. The fully connected layer is equipped with a probabilistic spike-timing-dependent plasticity learning rule. This layer represents the discriminative features through probabilistic, LIF neurons. To assess the discriminative power of the learned features, they are used in a hidden Markov model (HMM) for spoken digit recognition. The experimental results show performance above 96% that compares favorably with popular statistical feature extraction methods. Our results provide a novel demonstration of unsupervised feature acquisition in an SNN

Mechanochemical synthesis and ion transport properties of Na₃OX (X = Cl, Br, I and BH₄) antiperovskite solid electrolytes

The push towards the development of next-generation solid-state batteries has motivated the search for novel solid electrolyte materials. Sodium antiperovskites represent a structural family of ion conductors that has emerged as a result, with expected advantages in terms of composition tuning, electrochemical stability, mechanical softness and high ionic conductivity. Here, we report the mechanochemical synthesis of several materials in this structural family, including novel mixed-halide compositions such as Na3OCl0.5(BH4)0.5, Na3OBr0.5(BH4)0.5 Na3OI0.5(BH4)0.5 and Na3OCl0.33Br0.33(BH4)0.33. We rationalize the effect of halide substitution on the structure and ion transport properties of these materials through diffraction, impedance spectroscopy and molecular dynamics. We conclude with a discussion on Na3OBH4, which has recently been reported to be a fast ion conductor, owing to the rotational disorder of the complex superhalide anion BH4−. We are unable to reproduce the reported high ionic conductivity of Na3OBH4 neither by experiment nor ab initio simulation.</p

The Future Mortality of High Mortality Countries: A Model Incorporating Expert Arguments

This paper examines the future of mortality in the 65 countries still experiencing high mortality in 2010, as defined by a cutoff of 40 deaths before age five per thousand live births. Mortality declines in several countries stagnated or reversed in the last two decades of the twentieth century due mainly to HIV/AIDS. The forces underlying past mortality trends and affecting the future course of mortality are examined by reviewing the existing literature and reporting the results of the global survey and invited meeting, both involving mortality experts. The experts assessed the likelihood and weight of forces hypothesized to influence mortality. A statistical model is combined with these expert assessments to produce a set of mortality assumptions that are incorporated into the projections reported in this paper. This paper also addresses the limited availability of reliable data on age-specific mortality rates

Engaging land managers for nature conservation and renewal: A Practical guide for environmental groups

Also available on Zenodo via the DOI in this recordThe UK is in a climate emergency and ecological crisis. Key to addressing environmental problems, such as improving water quality and renewing biodiversity, involves tackling the way land is managed. But effective environmental land management depends on much more than scientific knowledge. It rests on an appropriate translation of the science by environmental groups and its effective implementation by land managers themselves. To achieve the latter, land managers must also be given ample opportunities to communicate their knowledge and expertise of the land. As such, it is essential for environmental groups to understand how best to engage with those key actors. The guidance provided in this report aims to support those groups in their engagement with land managers in such a way as to empower them to move towards more sustainable and regenerative land management practices. It comprises clear and concise guidance on effective engagement. This guidance draws heavily from the wealth of experience of Cornwall Wildlife Trust staff involved in the Upstream Thinking catchment management scheme funded by South West Water. The aim of this scheme is to improve water quality, increase biodiversity, and maintain viable farm businesses. Staff working on this scheme have developed immensely valuable engagement skills as part of their work with farmers in catchment systems over the past ten years. The document is organized into two sections: ‘engagement principles’ and ‘engagement steps.’ The former lists some key behavioural qualities for effective engagement with land managers. The latter lists the different steps and actions involved in building an effective engagement over time. The guidance applies to all types of environmental management plans involving a land manager and land adviser, including but not limited to those designed as part of existing agri-environment schemes (AES).Natural Environment Research Council (NERC

Crystal Structures, Local Atomic Environments, and Ion Diffusion Mechanisms of Scandium-Substituted Sodium Superionic Conductor (NASICON) Solid Electrolytes

The importance of exploring new solid electrolytes for all-solid-state batteries has led to significant interest in NASICON-type materials. Here, the Sc3+-substituted NASICON compositions Na3ScxZr2-x(SiO4)2-x(PO4)1+x (termed N3) and Na2ScyZr2-y(SiO4)1-y(PO4)2+y (termed N2) (x, y = 0 – 1) are studied as model Na+-ion conducting electrolytes for solid-state batteries. The influence of Sc3+ substitution on the crystal structures and local atomic environments has been characterized by powder X-ray diffraction (XRD) and neutron powder diffraction (NPD), as well as solid-state 23Na, 31P, and 29Si nuclear magnetic resonance (NMR) spectroscopy. A phase transition between 295 and 473 K from monoclinic C2/c to rhombohedral R c is observed for the N3 compositions, while N2 compositions crystallize in a rhombohedral R c unit cell in this temperature range. Alternating current (AC) impedance spectroscopy, molecular dynamics (MD) and high temperature 23Na NMR are in good agreement, showing that with a higher Sc3+ concentration, the ionic conductivity (about 10-4 S/cm at 473 K) decreases and the activation energy for ion diffusion increases. 23Na NMR experiments indicate that the nature of the Na+-ion motion is two-dimensional on the local atomic scale of NMR though the long-range diffusion pathways are three-dimensional. In addition, a combination of MD, bond valence, maximum entropy/Rietveld and van Hove correlation methods has been used, to reveal that the Na+-ion diffusion in these NASICON materials is three-dimensional and that there is a continuous exchange of sodium between Na(1) and Na(2) sites

FHR4-based immunoconjugates direct complement-dependent cytotoxicity and phagocytosis towards HER2-positive cancer cells

Directing selective complement activation towards tumour cells is an attractive strategy to promote their elimination. In the present work, we have generated heteromultimeric immunoconjugates that selectively activate the complement alternative pathway (AP) on tumour cells. We used the C4b-binding protein C-terminal-alpha-/beta-chain scaffold for multimerisation to generate heteromultimeric immunoconjugates displaying (a) a multivalent-positive regulator of the AP, the human factor H-related protein 4 (FHR4) with; (b) a multivalent targeting function directed against erbB2 (HER2); and (c) a monovalent enhanced GFP tracking function. Two distinct VHH targeting two different epitopes against HER2 and competing either with trastuzumab or with pertuzumab-recognising epitopes [VHH(T) or VHH(P)], respectively, were used as HER2 anchoring moieties. Optimised high-FHR4 valence heteromultimeric immunoconjugates [FHR4/VHH(T) or FHR4/VHH(P)] were selected by sequential cell cloning and a selective multistep His-Trap purification. Optimised FHR4-heteromultimeric immunoconjugates successfully overcame FH-mediated complement inhibition threshold, causing increased C3b deposition on SK-OV-3, BT474 and SK-BR3 tumour cells, and increased formation of lytic membrane attack complex densities and complement-dependent cytotoxicity (CDC). CDC varies according to the pattern expression and densities of membrane-anchored complement regulatory proteins on tumour cell surfaces. In addition, opsonised BT474 tumour cells were efficiently phagocytosed by macrophages through complement-dependent cell-mediated cytotoxicity. We showed that the degree of FHR4-multivalency within the multimeric immunoconjugates was the key element to efficiently compete and deregulate FH and FH-mediated convertase decay locally on tumour cell surface. FHR4 can thus represent a novel therapeutic molecule, when expressed as a multimeric entity and associated with an anchoring system, to locally shift the complement steady-state towards activation on tumour cell surface

Structural and Mechanistic Insights into Fast Lithium-Ion Conduction in Li4SiO4-Li3PO4 Solid Electrolytes.

Solid electrolytes that are chemically stable and have a high ionic conductivity would dramatically enhance the safety and operating lifespan of rechargeable lithium batteries. Here, we apply a multi-technique approach to the Li-ion conducting system (1-z)Li4SiO4-(z)Li3PO4 with the aim of developing a solid electrolyte with enhanced ionic conductivity. Previously unidentified superstructure and immiscibility features in high-purity samples are characterized by X-ray and neutron diffraction across a range of compositions (z = 0.0-1.0). Ionic conductivities from AC impedance measurements and large-scale molecular dynamics (MD) simulations are in good agreement, showing very low values in the parent phases (Li4SiO4 and Li3PO4) but orders of magnitude higher conductivities (10(-3) S/cm at 573 K) in the mixed compositions. The MD simulations reveal new mechanistic insights into the mixed Si/P compositions in which Li-ion conduction occurs through 3D pathways and a cooperative interstitial mechanism; such correlated motion is a key factor in promoting high ionic conductivity. Solid-state (6)Li, (7)Li, and (31)P NMR experiments reveal enhanced local Li-ion dynamics and atomic disorder in the solid solutions, which are correlated to the ionic diffusivity. These unique insights will be valuable in developing strategies to optimize the ionic conductivity in this system and to identify next-generation solid electrolytes.The ALISTORE ERI and CNRS are acknowledged for supporting Y.D. through a joint Ph.D. scholarship between Picardie (France) and Bath (UK). The authors thank D. Sheptyakov (PSI, Switzerland) and M. Bianchini (ILL-Grenoble, France) for assistance with neutron diffraction experiments, and M. T. Dunstan (Cambridge, UK) for assistance with NMR experiments. Financial support from the EPSRC Energy Materials Programme (Grant EP/K016288) is gratefully acknowledged. The HPC Materials Chemistry Consortium (EP/L000202) allowed use of the ARCHER facilities. O.P. and S.E. acknowledge support from a Marie Skłodowska-Curie Fellowship (H2020-MSCA-IF-2014-EF, no. 655444) and an ERASMUS+ scholarship, respectively.This is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/jacs.5b0444