The drivers of squirrelpox virus dynamics in its grey squirrel reservoir host

Manypathogensofconservationconcerncirculateendemicallywithinnaturalwildlifereservoirhostsanditisimperativetounderstandtheindividualandecologicaldriversofnaturaltransmissiondynamics,ifanythreattoarelatedendangeredspeciesistobeassessed.Ourstudyhighlightsthekeydriversofinfectionandsheddingdynamicsofsquirrelpoxvirus(SQPV)initsreservoirgreysquirrel(Sciurus carolinensis)population.ToclarifySQPV dynamics in this population, longitudinal data from a 16-month mark-recapture study were analysed,combining serology with real-time quantitative PCR to identify periods of acute viraemia and chronic viralshedding. At the population level, we found SQPV infection prevalence, viral load and shedding varied sea-sonally,peakinginautumnandearlyspring.Individually,SQPVwasshowntobeachronicinfectionin>80%ofgreysquirrels,withviralloadspersistingovertimeandboutsofpotentialrecrudescenceorreinfectionoc-curring.AkeyrecurringfactorsignificantlyassociatedwithSQPVinfectionriskwasthepresenceofco-infectingsquirrel adenovirus (ADV). In dual infected squirrels, longitudinal analysis showed that prior ADV viraemiaincreasedthesubsequentSQPVloadintheblood.However,therewasastrong,negativeassociationbetweenpriorADVviraemiaandsubsequentSQPVsheddingfromtheforearm,probablycausedbyADVprolongingtheSQPVacuteviraemicphase,sodelayingonsetofthechronicsheddingphase,andtherebyalteringviralsheddingpatternsoverthetimescalesexaminedhere.Hence,co-circulatingADVinfectionmaybeinvolvedinmediatingboththequantitativelevelsofSQPVinfectionandthetiminganddegreeofsubsequentinfectiousnessofgreysquirrels

Tailoring the electrochemical properties of 2D-hBN via physical linear defects: physicochemical, computational and electrochemical characterisation

Monolayer hexagonal-boron nitride films (2D-hBN) are typically reported within the literature to be electrochemically inactive due to their considerable band gap (ca. 5.2–5.8 eV). It is demonstrated herein that introducing physical linear defects (PLDs) upon the basal plane surface of 2D-hBN gives rise to electrochemically useful signatures. The reason for this transformation from insulator to semiconductor (inferred from physicochemical and computational characterisation) is likely due to full hydrogenation and oxygen passivation of the boron and/or nitrogen at edge sites. This results in a decrease in the band gap (from ca. 6.11 to 2.36/2.84 eV; theoretical calculated values, for the fully hydrogenated oxygen passivation at the N or B respectively). The 2D-hBN films are shown to be tailored through the introduction of PLDs, with the electrochemical behaviour dependent upon the surface coverage of edge plane-sites/defects, which is correlated with electrochemical performance towards redox probes (hexaammineruthenium(III) chloride and Fe2+/3+) and the hydrogen evolution reaction. This manuscript de-convolutes, for the first time, the fundamental electron transfer properties of 2D-hBN, demonstrating that through implementation of PLDs, one can beneficially tailor the electrochemical properties of this nanomateria

Automatic Tissue Segmentation with Deep Learning in Patients with Congenital or Acquired Distortion of Brain Anatomy

Brains with complex distortion of cerebral anatomy present several challenges to automatic tissue segmentation methods of T1-weighted MR images. First, the very high variability in the morphology of the tissues can be incompatible with the prior knowledge embedded within the algorithms. Second, the availability of MR images of distorted brains is very scarce, so the methods in the literature have not addressed such cases so far. In this work, we present the first evaluation of state-of-the-art automatic tissue segmentation pipelines on T1-weighted images of brains with different severity of congenital or acquired brain distortion. We compare traditional pipelines and a deep learning model, i.e. a 3D U-Net trained on normal-appearing brains. Unsurprisingly, traditional pipelines completely fail to segment the tissues with strong anatomical distortion. Surprisingly, the 3D U-Net provides useful segmentations that can be a valuable starting point for manual refinement by experts/neuroradiologists

Drifter observations in the summer time Bay of Biscay slope current

During the summer of 2012, 20 surface drifters drogued at 50 m depth were deployed on the continental slope to the north of the Bay of Biscay. Initially after release the drifters all crossed the slope, with 14 continuing equatorward, parallel to the slope following an absolute dynamic topography feature and 6 returning to the slope, in an eddy, visible in chlorophyll-a maps. Lagrangian statistics show an anisotropic flow field that becomes less tied to the absolute dynamic topography and increasingly dominated by diffusion and eddy processes. A weaker tie to the absolute dynamic topography allowed for total of 8 of the drifters crossed from the deep water onto the shelf, showing pathways for flow across the slope. A combination of drifter trajectories, absolute dynamic topography and chlorophyll-a concentration maps have been used to show that small anticyclonic eddies, tied to the complex slope topography provide a mechanism for on shelf transport. During the summer, the presence of these eddies can be seen in surface chlorophyll-a maps

Graphene Oxide Bulk-Modified Screen-Printed Electrodes Provide Beneficial Electroanalytical Sensing Capabilities

We demonstrate a facile methodology for the mass production of graphene oxide (GO) bulk-modified screen-printed electrodes (GO-SPEs) that are economical, highly reproducible and provide analytically useful outputs. Through fabricating GO-SPEs with varying percentage mass incorporations (2.5%, 5%, 7.5% and 10%) of GO, an electrocatalytic effect towards the chosen electroanalytical probes is observed, which increases with greater GO incorporated compared to bare/graphite SPEs. The optimum mass ratio of 10% GO to 90% carbon ink produces an electroanalytical signal towards dopamine (DA) and uric acid (UA) which is ca. ×10 greater in magnitude than that achievable at a bare/unmodified graphite SPE. Furthermore, 10% GO-SPEs exhibit a competitively low limit of detection (3σ) towards DA at ca. 81 nM, which is superior to that of a bare/unmodified graphite SPE at ca. 780 nM. The improved analytical response is attributed to the large number of oxygenated species inhabiting the edge and defect sites of the GO nanosheets, which are able to exhibit electrocatalytic responses towards inner-sphere electrochemical analytes. Our reported methodology is simple, scalable, and cost effective for the fabrication of GO-SPEs that display highly competitive LODs and are of significant interest for use in commercial and medicinal applications

Safety of streptococcus pyogenes vaccines: anticipating and overcoming challenges for clinical trials and post marketing monitoring

Streptococcus. pyogenes (Strep A) infections result in a vastly underestimated burden of acute and chronic disease globally. The Strep A Vaccine Global Consortium (SAVAC) mission is to accelerate the development of safe, effective and affordable S. pyogenes vaccines. The safety of vaccine recipients is of paramount importance. A single S. pyogenes vaccine clinical trial conducted in the 1960s raised important safety concerns. A SAVAC Safety Working Group was established to review the safety assessment methodology and results of more recent early phase clinical trials and to consider future challenges for vaccine safety assessments across all phases of vaccine development. No clinical or biological safety signals were detected in any of these early phase trials in the modern era. Improvements in vaccine safety assessments need further consideration, particularly for pediatric clinical trials, large-scale efficacy trials, and preparation for post-marketing pharmacovigilance

Electrochemical properties of vertically aligned graphenes: tailoring heterogeneous electron transfer through manipulation of the carbon microstructure

The structure of vertically aligned graphene electrodes is shown to directly affect heterogeneous electron transfer kinetics in terms of the density of active edge plane sites of the microstructure, where greater edge content results in favourable electrochemical behaviour

SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation

Macrophages exhibit a spectrum of activation states ranging from classical to alternative activation1. Alternatively, activated macrophages are involved in diverse pathophysiological processes such as confining tissue parasites2, improving insulin sensitivity3 or promoting an immune tolerant microenvironment that facilitates tumour growth and metastasis4. Recently, the role of metabolism regulating macrophage function has come into focus as both the classical and alternative activation programmes require specific regulated metabolic reprogramming5. While most of the studies regarding immunometabolism have focussed on the catabolic pathways activated to provide energy, little is known about the anabolic pathways mediating macrophage alternative activation. In this study, we show that the anabolic transcription factor sterol regulatory element binding protein 1 (SREBP1) is activated in response to the canonical Th2 cytokine interleukin 4 (IL-4) to trigger the de novo lipogenesis (DNL) programme, as a necessary step for macrophage alternative activation. Mechanistically, DNL consumes NADPH, partitioning it away from cellular antioxidant defences and raising ROS levels. ROS serves as a second messenger, signalling sufficient DNL, and promoting macrophage alternative activation. The pathophysiological relevance of this mechanism is validated by showing that SREBP1/DNL is essential for macrophage alternative activation in vivo in a helminth infection model.This work was supported by the British Heart Foundation (RG/18/7/33636), the MRC (MC_UU_00014/2) and the FP7 MITIN (223450). K.P. was a recipient of a fellowship from the Wellcome Trust. A.N.J.M. and E.J. are supported by the Wellcome Trust (100963/Z/13/Z) and the MRC (U105178805). J.L. is a recipient fellowship of the British Heart Foundation. A.D. was a Marie-Curie Early-Stage Researcher supported by the European Union’s Horizon 2020 research and innovation programme (675585 Marie-Curie ITN ‘SymBioSys’) to J.S.-R. A.K. is supported by the Wellcome Trust (106260/Z/14/Z) and an ERC award (648889). P.F. is supported by the Science Foundation Ireland (10/IN.1/B3004). The IMS Genomics and Transcriptomics and Histology cores (B.M.-A., B.Y.H.L. and M.K.M.) are funded by the UK MRC Metabolic Disease Unit (MRC_MC_UU_12012/5) and a Wellcome Trust Strategic Award (100574/Z/12/Z). The Disease Model Core is part of the MRC Metabolic Diseases Unit (MRC_MC_UU_12012/5) and Wellcome Trust Strategic Award (100574/Z/12/Z)

Systematic review of communication technologies to promote access and engagement of young people with diabetes into healthcare

Background: Research has investigated whether communication technologies (e.g. mobile telephony, forums, email) can be used to transfer digital information between healthcare professionals and young people who live with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on communication. Methods: Nine electronic databases were searched. Technologies were described and a narrative synthesis of all studies was undertaken. Results: Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony (n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n = 10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication technologies increased the frequency of contact between patient and healthcare professional. Findings were inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was available concerning behavioural and care coordination outcomes, although improvement in quality of life, patientcaregiver interaction, self-care and metabolic transmission were reported for some communication technologies. Conclusions: The breadth of study design and types of technologies reported make the magnitude of benefit and their effects on health difficult to determine. While communication technologies may increase the frequency of contact between patient and health care professional, it remains unclear whether this results in improved outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness and cost effectiveness of increasing the use of communication technologies between young people and healthcare professionals