Peripheral Innate Immune Activation Correlates With Disease Severity in GRN Haploinsufficiency.

Objective: To investigate associations between peripheral innate immune activation and frontotemporal lobar degeneration (FTLD) in progranulin gene (GRN) haploinsufficiency. Methods: In this cross-sectional study, ELISA was used to measure six markers of innate immunity (sCD163, CCL18, LBP, sCD14, IL-18, and CRP) in plasma from 30 GRN mutation carriers (17 asymptomatic, 13 symptomatic) and 29 controls. Voxel based morphometry was used to model associations between marker levels and brain atrophy in mutation carriers relative to controls. Linear regression was used to model relationships between plasma marker levels with mean frontal white matter integrity [fractional anisotropy (FA)] and the FTLD modified Clinical Dementia Rating Scale sum of boxes score (FTLD-CDR SB). Results: Plasma sCD163 was higher in symptomatic GRN carriers [mean 321 ng/ml (SD 125)] compared to controls [mean 248 ng/ml (SD 58); p < 0.05]. Plasma CCL18 was higher in symptomatic GRN carriers [mean 56.9 pg/ml (SD 19)] compared to controls [mean 40.5 pg/ml (SD 14); p < 0.05]. Elevation of plasma LBP was associated with white matter atrophy in the right frontal pole and left inferior frontal gyrus (p FWE corrected <0.05) in all mutation carriers relative to controls. Plasma LBP levels inversely correlated with bilateral frontal white matter FA (R2 = 0.59, p = 0.009) in mutation carriers. Elevation in plasma was positively correlated with CDR-FTLD SB (b = 2.27 CDR units/μg LBP/ml plasma, R2 = 0.76, p = 0.003) in symptomatic carriers. Conclusion: FTLD-GRN is associated with elevations in peripheral biomarkers of macrophage-mediated innate immunity, including sCD163 and CCL18. Clinical disease severity and white matter integrity are correlated with blood LBP, suggesting a role for peripheral immune activation in FTLD-GRN

Combinatorial realizations of crystals via torus actions on quiver varieties

Consider Kashiwara's crystal associated to a highest weight representation of a symmetric Kac-Moody algebra. There is a geometric realization of this object using Nakajima's quiver varieties, but in many particular cases it can also be realized by elementary combinatorial methods. Here we propose a framework for extracting combinatorial realizations from the geometric picture: We construct certain torus actions on the quiver varieties and use Morse theory to index the irreducible components by connected components of the subvariety of torus fixed points. We then discuss the case of affine sl(n). There the fixed point components are just points, and are naturally indexed by multi-partitions. There is some choice in our construction, leading to a family of combinatorial models for each highest weight crystal. Applying this construction to the crystal of the fundamental representation recovers a family of combinatorial realizations recently constructed by Fayers. This gives a more conceptual proof of Fayers' result as well as a generalization to higher level. We also discuss a relationship with Nakajima's monomial crystal.Comment: 23 pages, v2: added Section 8 on monomial crystals and some references; v3: many small correction

Remarkable resilience of forest structure and biodiversity following fire in the peri-urban bushland of Sydney, Australia

In rapidly urbanizing areas, natural vegetation becomes fragmented, making conservation planning challenging, particularly as climate change accelerates fire risk. We studied urban forest fragments in two threatened eucalypt‐dominated (scribbly gum woodland, SGW, and ironbark forest, IF) communities across ~2000 ha near Sydney, Australia, to evaluate effects of fire frequency (0– 4 in last 25 years) and time since fire (0.5 to >25 years) on canopy structure, habitat quality and biodiversity (e.g., species richness). Airborne lidar was used to assess canopy height and density, and ground‐based surveys of 148 (400 m2) plots measured leaf area index (LAI), plant species com‐ position and habitat metrics such as litter cover and hollow‐bearing trees. LAI, canopy density, litter, and microbiotic soil crust increased with time since fire in both communities, while tree and mistletoe cover increased in IF. Unexpectedly, plant species richness increased with fire frequency, owing to increased shrub richness which offset decreased tree richness in both communities. These findings indicate biodiversity and canopy structure are generally resilient to a range of times since fire and fire frequencies across this study area. Nevertheless, reduced arboreal habitat quality and subtle shifts in community composition of resprouters and obligate seeders signal early concern for a scenario of increasing fire frequency under climate change. Ongoing assessment of fire responses is needed to ensure that biodiversity, canopy structure and ecosystem function are maintained in the remaining fragments of urban forests under future climate change which will likely drive hotter and more frequent fires

Moduli in Exceptional SUSY Gauge Theories

The low energy structures of N=1 supersymmetric models with E_6, F_4 and E_7 gauge groups and fundamental irrep matter contents are studied herein. We identify sets of gauge invariant composites which label all flat directions in the confining/Higgs phases of these theories. The impossibility of mapping several of these primary operators rules out previously conjectured exceptional self duals reported in the literature.Comment: 20 pages, harvmac and tables macro

Global avian influenza surveillance in wild birds: A strategy to capture viral diversity

Wild birds play a major role in the evolution, maintenance, and spread of avian influenza viruses. However, surveillance for these viruses in wild birds is sporadic, geographically biased, and often limited to the last outbreak virus. To identify opportunities to optimize wild bird surveillance for understanding viral diversity, we reviewed responses to a World Organisation for Animal Health-administered survey, government reports to this organization, articles on Web of Knowledge, and the Influenza Research Database. At least 119 countries conducted avian influenza virus surveillance in wild birds during 2008-2013, but coordination and standardization was lacking among surveillance efforts, and most focused on limited subsets of influenza viruses. Given high financial and public health burdens of recent avian influenza outbreaks, we call for sustained, cost-effective investments in locations with high avian influenza diversity in wild birds and efforts to promote standardized sampling, testing, and reporting methods, including full-genome sequencing. (Résumé d'auteur

Digital Work Design

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)More and more academic studies and practitioner reports claim that human work is increasingly disrupted or even determined by information and communication technology (ICT) (Cascio and Montealegre 2016). This will make a considerable share of jobs currently performed by humans susceptible to automation (e.g., Frey and Osborne 2017; Manyika et al. 2017). These reports often sketch a picture of ‘machines taking over’ traditional domains like manufacturing, while ICT advances and capabilities seem to decide companies’ fate. Consequently, ICT is often put at the core of innovative efforts. While this applies to nearly all areas of workplace design, a recent popular example of increasing technology centricity is ‘Industry 4.0’, which is often delineated as ‘machines talking to computers’

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY) : a randomised, controlled, open-label, platform trial

Funding UK Research and Innovation (Medical Research Council) and National Institute for Health and Care Research (Grant ref: MC_PC_19056). Acknowledgements Above all, we would like to thank the patients who participated in this trial. We would also like to thank the many doctors, nurses, pharmacists, other allied health professionals, and research administrators at NHS hospital organisations across the whole of the UK, supported by staff at the National Institute of Health Research (NIHR) Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health & Social Care, the Intensive Care National Audit & Research Centre, Public Health Scotland, National Records Service of Scotland, the Secure Anonymised Information Linkage (SAIL) at University of Swansea, and the NHS in England, Scotland, Wales and Northern Ireland. The RECOVERY trial is supported by grants to the University of Oxford from UK Research and Innovation (UKRI) and NIHR (MC_PC_19056), the Wellcome Trust (Grant Ref: 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator, and by core funding provided by the NIHR Oxford Biomedical Research Centre, the Wellcome Trust, the Bill and Melinda Gates Foundation, the Foreign, Commonwealth and Development Office, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from UK Medical Research Council (MC_UU_0002/14). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. Tocilizumab was provided free of charge for this trial by Roche Products Limited. Regeneron Pharmaceuticals supported the trial through provision of casirivimab and imdevimab. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the UK Department of Health and Social Care. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The sponsor was not involved in study design, data collection and analysis or manuscript writing.Peer reviewe

Acromioclavicular joint reconstruction with coracoacromial ligament transfer using the docking technique

<p>Abstract</p> <p>Background</p> <p>Symptomatic Acromioclavicular (AC) dislocations have historically been surgically treated with Coracoclavicular (CC) ligament reconstruction with transfer of the Coracoacromial (CA) ligament. Tensioning the CA ligament is the key to success.</p> <p>Methods</p> <p>Seventeen patients with chronic, symptomatic Type III AC joint or acute Type IV and V injuries were treated surgically. The distal clavicle was resected and stabilized with CC ligament reconstruction using the CA ligament. The CA ligament was passed into the medullary canal and tensioned, using a modified 'docking' technique. Average follow-up was 29 months (range 12–57).</p> <p>Results</p> <p>Postoperative ASES and pain significantly improved in all patients (p = 0.001). Radiographically, 16 (94%) maintained reduction, and only 1 (6%) had a recurrent dislocation when he returned to karate 3 months postoperatively. His ultimate clinical outcome was excellent.</p> <p>Conclusion</p> <p>The docking procedure allows for tensioning of the transferred CA ligament and healing of the ligament in an intramedullary bone tunnel. Excellent clinical results were achieved, decreasing the risk of recurrent distal clavicle instability.</p