Project sanitarium:playing tuberculosis to its end game

Interdisciplinary and collaborative projects between industry and academia provide exceptional opportunities for learning. Project Sanitarium is a serious game for Windows PC and Tablet which aims to embed learning about tuberculosis (TB) through the player taking on the role of a doctor and solving cases across the globe. The project developed as a collaboration between staff and undergraduate students at the School of Arts, Media and Computer Games at Abertay University working with academics and researchers from the Infection Group at the University of St Andrews. The project also engaged industry partners Microsoft and DeltaDNA. The project aimed to educate students through a workplace simulation pedagogical model, encourage public engagement at events and through news coverage and lastly to prototype whether games could be used to simulate a virtual clinical trial. The project was embedded in the Abertay undergraduate programme where students are presented with real world problems to solve through design and technology. The result was a serious game prototype that utilized game design techniques and technology to demystify and educate players about the diagnosis and treatment of one of the world’s oldest and deadliest diseases, TB. Project Sanitarium aims to not only educate the player, but allows the player to become a part of a simulated drug trial that could potentially help create new treatments in the fight against TB. The game incorporates a mathematical model that is based on data from real-world drug trials. The interdisciplinary pedagogical model provides undergraduates with workplace simulation, wider industry collaboration and access to academic expertise to solve challenging and complex problems

The phenotype of circulating follicular-helper T cells in patients with rheumatoid arthritis defines CD200 as a potential therapeutic target

Rheumatoid arthritis (RA) is a systemic autoimmune disease primarily affecting synovial joints in which the development of autoantibodies represents a failure of normal tolerance mechanisms, suggesting a role for follicular helper T cells (TFH) in the genesis of autoimmunity. To determine whether quantitative or qualitative abnormalities in the circulating TFH cell population exist, we analysed by flow cytometry the number and profile of these cells in 35 patients with RA and 15 matched controls. Results were correlated with patient characteristics, including the presence of autoantibodies, disease activity, and treatment with biologic agents. Circulating TFH cells from patients with RA show significantly increased expression of the immunoglobulin superfamily receptor CD200, with highest levels seen in seropositive patients (P=0.0045) and patients treated with anti-TNFα agents (P=0.0008). This occurs in the absence of any change in TFH numbers or overt bias towards Th1, Th2, or Th17 phenotypes. CD200 levels did not correlate with DAS28 scores (P=0.887). Although the number of circulating TFH cells is not altered in the blood of patients with RA, the TFH cells have a distinct phenotype. These differences associate TFH cells with the pathogenesis of RA and support the relevance of the CD200/CD200R signalling pathway as a potential therapeutic target

Waveguide-integrated silicon T centres

The performance of modular, networked quantum technologies will be strongly dependent upon the quality of their quantum light-matter interconnects. Solid-state colour centres, and in particular T centres in silicon, offer competitive technological and commercial advantages as the basis for quantum networking technologies and distributed quantum computing. These newly rediscovered silicon defects offer direct telecommunications-band photonic emission, long-lived electron and nuclear spin qubits, and proven native integration into industry-standard, CMOS-compatible, silicon-on-insulator (SOI) photonic chips at scale. Here we demonstrate further levels of integration by characterizing T centre spin ensembles in single-mode waveguides in SOI. In addition to measuring long spin T_1 times, we report on the integrated centres' optical properties. We find that the narrow homogeneous linewidth of these waveguide-integrated emitters is already sufficiently low to predict the future success of remote spin-entangling protocols with only modest cavity Purcell enhancements. We show that further improvements may still be possible by measuring nearly lifetime-limited homogeneous linewidths in isotopically pure bulk crystals. In each case the measured linewidths are more than an order of magnitude lower than previously reported and further support the view that high-performance, large-scale distributed quantum technologies based upon T centres in silicon may be attainable in the near term

Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis.

Psoriatic arthritis (PsA) is a debilitating immune-mediated inflammatory arthritis of unknown pathogenesis commonly affecting patients with skin psoriasis. Here we use complementary single-cell approaches to study leukocytes from PsA joints. Mass cytometry demonstrates a 3-fold expansion of memory CD8 T cells in the joints of PsA patients compared to peripheral blood. Meanwhile, droplet-based and plate-based single-cell RNA sequencing of paired T cell receptor alpha and beta chain sequences show pronounced CD8 T cell clonal expansions within the joints. Transcriptome analyses find these expanded synovial CD8 T cells to express cycling, activation, tissue-homing and tissue residency markers. T cell receptor sequence comparison between patients identifies clonal convergence. Finally, chemokine receptor CXCR3 is upregulated in the expanded synovial CD8 T cells, while two CXCR3 ligands, CXCL9 and CXCL10, are elevated in PsA synovial fluid. Our data thus provide a quantitative molecular insight into the cellular immune landscape of psoriatic arthritis

Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis

Psoriatic arthritis (PsA) is a debilitating immune-mediated inflammatory arthritis of unknown pathogenesis commonly affecting patients with skin psoriasis. Here we use complementary single-cell approaches to study leukocytes from PsA joints. Mass cytometry demonstrates a 3-fold expansion of memory CD8 T cells in the joints of PsA patients compared to peripheral blood. Meanwhile, droplet-based and plate-based single-cell RNA sequencing of paired T cell receptor alpha and beta chain sequences show pronounced CD8 T cell clonal expansions within the joints. Transcriptome analyses find these expanded synovial CD8 T cells to express cycling, activation, tissue-homing and tissue residency markers. T cell receptor sequence comparison between patients identifies clonal convergence. Finally, chemokine receptor CXCR3 is upregulated in the expanded synovial CD8 T cells, while two CXCR3 ligands, CXCL9 and CXCL10, are elevated in PsA synovial fluid. Our data thus provide a quantitative molecular insight into the cellular immune landscape of psoriatic arthritis

Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes

Musculoskeletal diseases affect up to 20% of adults worldwide. The gut microbiome has been implicated in inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity in the gut affects inflammatory arthritis. To characterize the community structure and associated functional processes driving gut microbial involvement in arthritis, the Inflammatory Arthritis Microbiome Consortium investigated 440 stool shotgun metagenomes comprising 221 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and 219 healthy controls and individuals with joint pain without an underlying inflammatory cause. Diagnosis explained about 2% of gut taxonomic variability, which is comparable in magnitude to inflammatory bowel disease. We identified several candidate microbes with differential carriage patterns in patients with elevated blood markers for inflammation. Our results confirm and extend previous findings of increased carriage of typically oral and inflammatory taxa and decreased abundance and prevalence of typical gut clades, indicating that distal inflammatory conditions, as well as local conditions, correspond to alterations to the gut microbial composition. We identified several differentially encoded pathways in the gut microbiome of patients with inflammatory arthritis, including changes in vitamin B salvage and biosynthesis and enrichment of iron sequestration. Although several of these changes characteristic of inflammation could have causal roles, we hypothesize that they are mainly positive feedback responses to changes in host physiology and immune homeostasis. By connecting taxonomic alternations to functional alterations, this work expands our understanding of the shifts in the gut ecosystem that occur in response to systemic inflammation during arthritis

Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes

Musculoskeletal diseases affect up to 20% of adults worldwide. The gut microbiome has been implicated in inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity in the gut affects inflammatory arthritis. To characterize the community structure and associated functional processes driving gut microbial involvement in arthritis, the Inflammatory Arthritis Microbiome Consortium investigated 440 stool shotgun metagenomes comprising 221 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and 219 healthy controls and individuals with joint pain without an underlying inflammatory cause. Diagnosis explained about 2% of gut taxonomic variability, which is comparable in magnitude to inflammatory bowel disease. We identified several candidate microbes with differential carriage patterns in patients with elevated blood markers for inflammation. Our results confirm and extend previous findings of increased carriage of typically oral and inflammatory taxa and decreased abundance and prevalence of typical gut clades, indicating that distal inflammatory conditions, as well as local conditions, correspond to alterations to the gut microbial composition. We identified several differentially encoded pathways in the gut microbiome of patients with inflammatory arthritis, including changes in vitamin B salvage and biosynthesis and enrichment of iron sequestration. Although several of these changes characteristic of inflammation could have causal roles, we hypothesize that they are mainly positive feedback responses to changes in host physiology and immune homeostasis. By connecting taxonomic alternations to functional alterations, this work expands our understanding of the shifts in the gut ecosystem that occur in response to systemic inflammation during arthritis

Advancing research paradigms and pathophysiological pathways in psoriatic arthritis and ankylosing spondylitis: Proceedings of the 2017 Platform for the Exchange of Expertise and Research (PEER) Meeting

The seronegative spondyloarthropathies, including psoriatic arthritis (PsA) and ankylosing spondylitis (AS), are characterized by varied clinical symptoms, severity, and disease course [1], [2]. Diagnosis and monitoring can be challenging because there is no definitive laboratory biomarker for reliably measuring inflammation or other disease processes associated with spondyloarthropathies. Over time, many patients with PsA and AS eventually experience significant disability and impaired quality of life [1], [2]. This may be partially accounted for by delays in diagnosis and subsequent treatment [3], as well as the presence of comorbidities. In recent years, research efforts aimed at identifying risk factors for PsA, including clinical, imaging, genetic, and laboratory assessments, have yielded major advances. The Platform for the Exchange of Expertise and Research (PEER) was formed to facilitate the exchange of research insights, sharing of expertise, and discussion of unmet needs in rheumatology research. The objective of the current report is to provide an overview of the 2017 PEER meeting, which was held on May 19–20, 2017, in London, UK, and highlighted the most up-to-date research findings regarding PsA and AS pathophysiology, early detection, comorbidities, and treatment