A novel framework employing deep multi-attention channels network for the autonomous detection of metastasizing cells through fluorescence microscopy

We developed a transparent computational large-scale imaging-based framework that can distinguish between normal and metastasizing human cells. The method relies on fluorescence microscopy images showing the spatial organization of actin and vimentin filaments in normal and metastasizing single cells, using a combination of multi-attention channels network and global explainable techniques. We test a classification between normal cells (Bj primary fibroblast), and their isogenically matched, transformed and invasive counterpart (BjTertSV40TRasV12). Manual annotation is not trivial to automate due to the intricacy of the biologically relevant features. In this research, we utilized established deep learning networks and our new multi-attention channel architecture. To increase the interpretability of the network - crucial for this application area - we developed an interpretable global explainable approach correlating the weighted geometric mean of the total cell images and their local GradCam scores. The significant results from our analysis unprecedently allowed a more detailed, and biologically relevant understanding of the cytoskeletal changes that accompany oncogenic transformation of normal to invasive and metastasizing cells. We also paved the way for a possible spatial micrometre-level biomarker for future development of diagnostic tools against metastasis (spatial distribution of vimentin)

Case Study - Spiking Neural Network Hardware System for Structural Health Monitoring

This case study provides feasibility analysis of adapting Spiking Neural Networks (SNN) based Structural Health Monitoring (SHM) system to explore low-cost solution for inspection of structural health of damaged buildings which survived after natural disaster that is, earthquakes or similar activities. Various techniques are used to detect the structural health status of a building for performance benchmarking, including different feature extraction methods and classification techniques (e.g., SNN, K-means and artificial neural network etc.). The SNN is utilized to process the sensory data generated from full-scale seven-story reinforced concrete building to verify the classification performances. Results show that the proposed SNN hardware has high classification accuracy, reliability, longevity and low hardware area overhead

The Mouse Gastrointestinal Bacteria Catalogue enables translation between the mouse and human gut microbiotas via functional mapping.

Funder: Royal SocietyHuman health and disease have increasingly been shown to be impacted by the gut microbiota, and mouse models are essential for investigating these effects. However, the compositions of human and mouse gut microbiotas are distinct, limiting translation of microbiota research between these hosts. To address this, we constructed the Mouse Gastrointestinal Bacteria Catalogue (MGBC), a repository of 26,640 high-quality mouse microbiota-derived bacterial genomes. This catalog enables species-level analyses for mapping functions of interest and identifying functionally equivalent taxa between the microbiotas of humans and mice. We have complemented this with a publicly deposited collection of 223 bacterial isolates, including 62 previously uncultured species, to facilitate experimental investigation of individual commensal bacteria functions in vitro and in vivo. Together, these resources provide the ability to identify and test functionally equivalent members of the host-specific gut microbiotas of humans and mice and support the informed use of mouse models in human microbiota research.Sir Henry Dale Fellowship jointly funded by Wellcome Trust and Royal Society [206245/Z/17/Z]. Rosetrees Trust [A2194]. Wellcome Trust [098051]

Germinal center B cells govern their own fate via antibody feedback

Affinity maturation of B cells in germinal centers (GCs) is a process of evolution, involving random mutation of immunoglobulin genes followed by natural selection by T cells. Only B cells that have acquired antigen are able to interact with T cells. Antigen acquisition is dependent on the interaction of B cells with immune complexes inside GCs. It is not clear how efficient selection of B cells is maintained while their affinity matures. Here we show that the B cells’ own secreted products, antibodies, regulate GC selection by limiting antigen access. By manipulating the GC response with monoclonal antibodies of defined affinities, we show that antibodies in GCs are in affinity-dependent equilibrium with antibodies produced outside and that restriction of antigen access influences B cell selection, seen as variations in apoptosis, plasma cell output, T cell interaction, and antibody affinity. Feedback through antibodies produced by GC-derived plasma cells can explain how GCs maintain an adequate directional selection pressure over a large range of affinities throughout the course of an immune response, accelerating the emergence of B cells of highest affinities. Furthermore, this mechanism may explain how spatially separated GCs communicate and how the GC reaction terminates

Measurement of magnetic cavitation driven by heat flow in a plasma

We describe the direct measurement of the expulsion of a magnetic field from a plasma driven by heat flow. Using a laser to heat a column of gas within an applied magnetic field, we isolate Nernst advection and show how it changes the field over a nanosecond timescale. Reconstruction of the magnetic field map from proton radiographs demonstrates that the field is advected by heat flow in advance of the plasma expansion. This changes the dynamics of high energy density plasmas, in which heat flows and fields are strongly coupled, and may disrupt magnetised inertial confinement fusion schemes

The antiviral restriction factor IFN-induced transmembrane protein 3 prevents cytokine-driven CMV pathogenesis

The antiviral restriction factor IFN-induced transmembrane protein 3 (IFITM3) inhibits cell entry of a number of viruses, and genetic diversity within IFITM3 determines susceptibility to viral disease in humans. Here, we used the murine CMV (MCMV) model of infection to determine that IFITM3 limits herpesvirus-associated pathogenesis without directly preventing virus replication. Instead, IFITM3 promoted antiviral cellular immunity through the restriction of virus-induced lymphopenia, apoptosis-independent NK cell death, and loss of T cells. Viral disease in Ifitm3–/– mice was accompanied by elevated production of cytokines, most notably IL-6. IFITM3 inhibited IL-6 production by myeloid cells in response to replicating and nonreplicating virus as well as following stimulation with the TLR ligands Poly(I:C) and CpG. Although IL-6 promoted virus-specific T cell responses, uncontrolled IL-6 expression in Ifitm3–/– mice triggered the loss of NK cells and subsequently impaired control of MCMV replication. Thus, IFITM3 represents a checkpoint regulator of antiviral immunity that controls cytokine production to restrict viral pathogenesis. These data suggest the utility of cytokine-targeting strategies in the treatment of virus-infected individuals with impaired IFITM3 activity

Comparing Notes: Recording and Criticism

This chapter charts the ways in which recording has changed the nature of music criticism. It both provides an overview of the history of recording and music criticism, from the advent of Edison’s Phonograph to the present day, and examines the issues arising from this new technology and the consequent transformation of critical thought and practice

Electronic cigarettes for smoking cessation

Background Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e‐liquid. Some people who smoke use ECs to stop or reduce smoking, but some organizations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit and if they are safe to use for this purpose. This is an update of a review first published in 2014. Objectives To examine the effectiveness, tolerability, and safety of using electronic cigarettes (ECs) to help people who smoke achieve long‐term smoking abstinence. Search methods We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO to 1 February 2021, together with reference‐checking and contact with study authors. Selection criteria We included randomized controlled trials (RCTs) and randomized cross‐over trials in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. To be included, studies had to report abstinence from cigarettes at six months or longer and/or data on adverse events (AEs) or other markers of safety at one week or longer. Data collection and analysis We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow‐up, adverse events (AEs), and serious adverse events (SAEs). Secondary outcomes included changes in carbon monoxide, blood pressure, heart rate, blood oxygen saturation, lung function, and levels of known carcinogens/toxicants. We used a fixed‐effect Mantel‐Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data from these studies in meta‐analyses. Main results We included 56 completed studies, representing 12,804 participants, of which 29 were RCTs. Six of the 56 included studies were new to this review update. Of the included studies, we rated five (all contributing to our main comparisons) at low risk of bias overall, 41 at high risk overall (including the 25 non‐randomized studies), and the remainder at unclear risk. There was moderate‐certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.25 to 2.27; I2 = 0%; 3 studies, 1498 participants). In absolute terms, this might translate to an additional four successful quitters per 100 (95% CI 2 to 8). There was low‐certainty evidence (limited by very serious imprecision) that the rate of occurrence of AEs was similar) (RR 0.98, 95% CI 0.80 to 1.19; I2 = 0%; 2 studies, 485 participants). SAEs occurred rarely, with no evidence that their frequency differed between nicotine EC and NRT, but very serious imprecision led to low certainty in this finding (RR 1.37, 95% CI 0.77 to 2.41: I2 = n/a; 2 studies, 727 participants). There was moderate‐certainty evidence, again limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non‐nicotine EC (RR 1.70, 95% CI 1.03 to 2.81; I2 = 0%; 4 studies, 1057 participants). In absolute terms, this might again lead to an additional four successful quitters per 100 (95% CI 0 to 11). These trials mainly used older EC with relatively low nicotine delivery. There was moderate‐certainty evidence of no difference in the rate of AEs between these groups (RR 1.01, 95% CI 0.91 to 1.11; I2 = 0%; 3 studies, 601 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 0.60, 95% CI 0.15 to 2.44; I2 = n/a; 4 studies, 494 participants). Compared to behavioral support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.70, 95% CI 1.39 to 5.26; I2 = 0%; 5 studies, 2561 participants). In absolute terms this represents an increase of seven per 100 (95% CI 2 to 17). However, this finding was of very low certainty, due to issues with imprecision and risk of bias. There was no evidence that the rate of SAEs differed, but some evidence that non‐serious AEs were more common in people randomized to nicotine EC (AEs: RR 1.22, 95% CI 1.12 to 1.32; I2 = 41%, low certainty; 4 studies, 765 participants; SAEs: RR 1.17, 95% CI 0.33 to 4.09; I2 = 5%; 6 studies, 1011 participants, very low certainty). Data from non‐randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate with continued use. Very few studies reported data on other outcomes or comparisons and hence evidence for these is limited, with confidence intervals often encompassing clinically significant harm and benefit. Authors' conclusions There is moderate‐certainty evidence that ECs with nicotine increase quit rates compared to ECs without nicotine and compared to NRT. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the size of effect, particularly when using modern EC products. Confidence intervals were for the most part wide for data on AEs, SAEs and other safety markers, though evidence indicated no difference in AEs between nicotine and non‐nicotine ECs. Overall incidence of SAEs was low across all study arms. We did not detect any clear evidence of harm from nicotine EC, but longest follow‐up was two years and the overall number of studies was small. The evidence is limited mainly by imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway. To ensure the review continues to provide up‐to‐date information, this review is now a living systematic review. We run searches monthly, with the review updated when relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status

Wider Still and Wider: British Music Criticism since the Second World War

This chapter provides the first historical examination of music criticism in Britain since the Second World War. In the process, it also challenges the simplistic prevailing view of this being a period of decline from a golden age in music criticism