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

(Re)conceptualising physical activity participation as career

Physical activity is increasingly positioned as playing an important role in preventing and mitigating many of the decrements associated with biological ageing. As a result, public health messages encourage older people to remain active in later life. Despite this, physical activity participation rates among older adults are low. This may be in part related to the conventional approach to understanding physical activity participation as a product of motivation. We contend that this approach does not allow for a deeper exploration of the wider structural, historical and discursive contexts in which physical activity participation occurs. Therefore, we propose that physical activity can be reconceptualised as a career. Through a synthesis of findings from four studies exploring physical activity experiences in later life, we demonstrate that beginning and maintaining a physical activity career requires a disposition towards physical activity, the legitimation of physically active practices and dealing with contingencies. In addition, we demonstrate that maintaining a physical activity career requires investment and deliberation to adapt physical activity practices continually within an individual's own personal biography. As such, we conclude that current strategies to promote physical activity to older adults are unlikely to result in increased levels of participation. To promote physical activity to older adults an understanding of how structural, cultural and historical contexts influence participation is needed

A hybrid individual-based mathematical model to study bladder infections

RB was supported by a fellowship funded by the Medical Research Council, MR/P014704/1, and also acknowledges funding from the Academy of Medical Sciences (London), the Wellcome Trust (London), the UK Government Department of Business, Energy and Industrial Strategy (London), the British Heart Foundation (London), and the Global Challenges Research Fund (Swindon, UK; grant number SBF003\1052). TL gratefully acknowledges support from the Italian Ministry of University and Research (MUR) through the grant Dipartimenti di Eccellenza 2018-2022 (Project no. E11G18000350001) and the PRIN 2020 project (No. 2020JLWP23) Integrated Mathematical Approaches to Socio-Epidemiological Dynamics (CUP: E15F21005420006).Introduction: Bladder infections are common, affecting millions each year, and are often recurrent problems. Methods: We have developed a spatial mathematical framework consisting of a hybrid individual-based model to simulate these infections in order to understand more about the bacterial mechanisms and immune dynamics. We integrate a varying bacterial replication rate and model bacterial shedding as an immune mechanism. Results: We investigate the effect that varying the initial bacterial load has on infection outcome, where we find that higher bacterial burden leads to poorer outcomes, but also find that only a single bacterium is needed to establish infection in some cases. We also simulate an immunocompromised environment, confirming the intuitive result that bacterial spread typically progresses at a higher rate. Conclusions: With future model developments, this framework is capable of providing new clinical insight into bladder infections.Publisher PDFPeer reviewe

Exploring the utility of assistive artificial intelligence for ultrasound scanning in regional anesthesia

This work was funded by Intelligent Ultrasound Limited (Cardiff, UK). Data from this study were included in medical device regulatory approval submissions in the USA.Introduction: Ultrasound-guided regional anesthesia (UGRA) involves the acquisition and interpretation of ultrasound images to delineate sonoanatomy. This study explores the utility of a novel artificial intelligence (AI) device designed to assist in this task (ScanNav Anatomy Peripheral Nerve Block; ScanNav), which applies a color overlay on real-time ultrasound to highlight key anatomical structures. Methods: Thirty anesthesiologists, 15 non-experts and 15 experts in UGRA, performed 240 ultrasound scans across nine peripheral nerve block regions. Half were performed with ScanNav. After scanning each block region, participants completed a questionnaire on the utility of the device in relation to training, teaching, and clinical practice in ultrasound scanning for UGRA. Ultrasound and color overlay output were recorded from scans performed with ScanNav. Experts present during the scans (real-time experts) were asked to assess potential for increased risk associated with use of the device (eg, needle trauma to safety structures). This was compared with experts who viewed the AI scans remotely. Results: Non-experts were more likely to provide positive and less likely to provide negative feedback than experts (p=0.001). Positive feedback was provided most frequently by non-experts on the potential role for training (37/60, 61.7%); for experts, it was for its utility in teaching (30/60, 50%). Real-time and remote experts reported a potentially increased risk in 12/254 (4.7%) vs 8/254 (3.1%, p=0.362) scans, respectively. Discussion: ScanNav shows potential to support non-experts in training and clinical practice, and experts in teaching UGRA. Such technology may aid the uptake and generalizability of UGRA. TRIAL REGISTRATION NUMBER: NCT04918693.Publisher PDFPeer reviewe

A photonic platform for donor spin qubits in silicon

Donor spins in silicon are highly competitive qubits for upcoming quantum technologies, offering complementary metal-oxide semiconductor compatibility, coherence (T2) times of minutes to hours, and simultaneous initialization, manipulation, and readout fidelities near ~99.9%. This allows for many quantum error correction protocols, which will be essential for scale-up. However, a proven method of reliably coupling spatially separated donor qubits has yet to be identified. We present a scalable silicon-based platform using the unique optical properties of “deep” chalcogen donors. For the prototypical 77Se+ donor, we measure lower bounds on the transition dipole moment and excited-state lifetime, enabling access to the strong coupling limit of cavity quantum electrodynamics using known silicon photonic resonator technology and integrated silicon photonics. We also report relatively strong photon emission from this same transition. These results unlock clear pathways for silicon-based quantum computing, spin-to-photon conversion, photonic memories, integrated single-photon sources, and all-optical switches

Characterization of the Si:Se+ Spin-Photon Interface

Silicon is the most-developed electronic and photonic technological platform and hosts some of the highest-performance spin and photonic qubits developed to date. A hybrid quantum technology harnessing an efficient spin-photon interface in silicon would unlock considerable potential by enabling ultralong-lived photonic memories, distributed quantum networks, microwave-to-optical photon converters, and spin-based quantum processors, all linked with integrated silicon photonics. However, the indirect band gap of silicon makes identification of efficient spin-photon interfaces nontrivial. Here we build upon the recent identification of chalcogen donors as a promising spin-photon interface in silicon. We determine that the spin-dependent optical degree of freedom has a transition dipole moment stronger than previously thought [here 1.96(8) D], and the spin T1 lifetime in low magnetic fields is longer than previously thought [here longer than 4.6(1.5) h]. We furthermore determine the optical excited-state lifetime [7.7(4) ns], and therefore the natural radiative efficiency [0.80(9)%], and by measuring the phonon sideband determine the zero-phonon emission fraction [16(1)%]. Taken together, these parameters indicate that an integrated quantum optoelectronic platform based on chalcogen-donor qubits in silicon is well within reach of current capabilities

Pilot study exploring if an augmented reality NeedleTrainer device improves novice performance of a simulated central venous catheter insertion on a phantom

Introduction: Needle insertion and visualisation skills needed for ultrasound (US)-guided procedures can be challenging to acquire. The novel NeedleTrainer device superimposes a digital holographic needle on a real-time US image display without puncturing a surface. The aim of this randomised control study was to compare the success of trainees performing a simulated central venous catheter insertion on a phantom either with or without prior NeedleTrainer device practice. Methods: West of Scotland junior trainees who had not performed insertion of a central venous catheter were randomised into two groups (n=20). Participants undertook standardized online training through a pre-recorded video and training on how to handle a US probe. Group 1 had 10 minutes of supervised training with the NeedleTrainer device. Group 2 were a control group. Participants were assessed on needle insertion to a pre-defined target vein in a phantom. The outcome measures were the time taken for needle placement (secs), number of needle passes (n), operator confidence (0-10), assessor confidence (0-10), and NASA task load index score. Results: The mean mental demand score in the control group was 7.65 (SD 3.5) compared to 12.8 (SD 2.2, p=0.005) in the NeedleTrainer group. There was no statistical difference between the groups in any of the other outcome measures. Discussion: This was a small pilot study, and small participant numbers may have impacted the statistical significance. There is natural variation of skill within participants that could not have been controlled for. The difference in pressure needed using the NeedleTrainer compared to a real needle may impact the outcome measures

Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele.

IL-7 is a key factor in T cell immunity and common variants at IL7R, encoding its receptor, are associated with autoimmune disease susceptibility. IL7R mRNA is induced in stimulated monocytes, yet a function for IL7R in monocyte biology remains unexplored. Here we characterize genetic regulation of IL7R at the protein level in healthy individuals, and find that monocyte surface and soluble IL7R (sIL7R) are markedly induced by lipopolysaccharide. In monocytes, both surface IL7R and sIL7R expression strongly associate with allelic carriage of rs6897932, a disease-associated IL7R polymorphism. Monocytes produce more sIL7R than CD4 + T cells, and the amount is additionally correlated with the expression of DDX39A, encoding a splicing factor. Synovial fluid-derived monocytes from patients with spondyloarthritis are enriched for IL7R+ cells with a unique transcriptional profile that overlaps with IL-7-induced gene sets. Our data thus suggest a previously unappreciated function for monocytes in IL-7 biology and IL7R-associated diseases