Say A Little Prayer For Me / music by Horatio Nicholls; words by Joseph George Gilbert

Key of G. Cover: a drawing of a woman portrait and a Candle (two white discs); Publisher: M. Witmark and Sons (New York)https://egrove.olemiss.edu/sharris_e/1010/thumbnail.jp

Three red suns in the sky: A transiting, terrestrial planet in a triple M-dwarf system at 6.9 pc

We present the discovery from Transiting Exoplanet Survey Satellite (TESS) data of LTT 1445Ab. At a distance of 6.9 pc, it is the second nearest transiting exoplanet system found to date, and the closest one known for which the primary is an M dwarf. The host stellar system consists of three mid-to-late M dwarfs in a hierarchical configuration, which are blended in one TESS pixel. We use MEarth data and results from the Science Processing Operations Center data validation report to determine that the planet transits the primary star in the system. The planet has a radius of ${1.38}_{-0.12}^{+0.13}$ ${R}_{\oplus }$, an orbital period of ${5.35882}_{-0.00031}^{+0.00030}$ days, and an equilibrium temperature of ${433}_{-27}^{+28}$ K. With radial velocities from the High Accuracy Radial Velocity Planet Searcher, we place a 3σ upper mass limit of 8.4 ${M}_{\oplus }$ on the planet. LTT 1445Ab provides one of the best opportunities to date for the spectroscopic study of the atmosphere of a terrestrial world. We also present a detailed characterization of the host stellar system. We use high-resolution spectroscopy and imaging to rule out the presence of any other close stellar or brown dwarf companions. Nineteen years of photometric monitoring of A and BC indicate a moderate amount of variability, in agreement with that observed in the TESS light-curve data. We derive a preliminary astrometric orbit for the BC pair that reveals an edge-on and eccentric configuration. The presence of a transiting planet in this system hints that the entire system may be co-planar, implying that the system may have formed from the early fragmentation of an individual protostellar core.Accepted manuscrip

The role of cell death in the pathogenesis of autoimmune disease: HMGB1 and microparticles as intercellular mediators of inflammation

Cell death is critical to normal homeostasis, although this process, when increased aberrantly, can lead to the production of pro-inflammatory mediators promoting autoimmunity. Two novel intercellular mediators of inflammation generated during cell death are high mobility group box 1 (HMGB1) protein and microparticles (MPs). HMGB1 is a nuclear protein that functions in transcription when inside the nucleus but takes on pro-inflammatory properties when released during cell death. Microparticles are small, membrane-bound structures that extrude from cells when they die and contain cell surface proteins and nuclear material from their parent cells. MPs circulate widely throughout the vasculature and mediate long-distance communication between cells. Both MPs and HMGB1 have been implicated in the pathogenesis of a broad spectrum of inflammatory diseases, including the prototypic autoimmune conditions systemic lupus erythematosus and rheumatoid arthritis. Given their range of activity and association with active disease, both structures may prove to be targets for effective therapy in these and other disorders

TOI-4641b: An Aligned Warm Jupiter Orbiting a Bright (V=7.5) Rapidly Rotating F-star

We report the discovery of TOI-4641b, a warm Jupiter transiting a rapidly rotating F-type star with a stellar effective temperature of 6560 K. The planet has a radius of 0.73 $R_{Jup}$, a mass smaller than 3.87 $M_{Jup}$ $(3\sigma)$, and a period of 22.09 days. It is orbiting a bright star (V=7.5 mag) on a circular orbit with a radius and mass of 1.73 $R_{\odot}$ and 1.41 $M_{\odot}$. Follow-up ground-based photometry was obtained using the Tierras Observatory. Two transits were also observed with the Tillinghast Reflector Echelle Spectrograph (TRES), revealing the star to have a low projected spin-orbit angle ($\lambda$=$1.41^{+0.76}_{-0.76}$ degrees). Such obliquity measurements for stars with warm Jupiters are relatively few, and may shed light on the formation of warm Jupiters. Among the known planets orbiting hot and rapidly-rotating stars, TOI-4641b is one of the longest-period planets to be thoroughly characterized. Unlike hot Jupiters around hot stars which are more often misaligned, the warm Jupiter TOI-4641b is found in a well-aligned orbit. Future exploration of this parameter space can add one more dimension to the star-planet orbital obliquity distribution that has been well-sampled for hot Jupiters.Comment: Accepted MNRA

HIV-1 Subtype C-Infected Individuals Maintaining High Viral Load as Potential Targets for the “Test-and-Treat” Approach to Reduce HIV Transmission

The first aim of the study is to assess the distribution of HIV-1 RNA levels in subtype C infection. Among 4,348 drug-naïve HIV-positive individuals participating in clinical studies in Botswana, the median baseline plasma HIV-1 RNA levels differed between the general population cohorts (4.1–4.2 log10) and cART-initiating cohorts (5.1–5.3 log10) by about one log10. The proportion of individuals with high (≥50,000 (4.7 log10) copies/ml) HIV-1 RNA levels ranged from 24%–28% in the general HIV-positive population cohorts to 65%–83% in cART-initiating cohorts. The second aim is to estimate the proportion of individuals who maintain high HIV-1 RNA levels for an extended time and the duration of this period. For this analysis, we estimate the proportion of individuals who could be identified by repeated 6- vs. 12-month-interval HIV testing, as well as the potential reduction of HIV transmission time that can be achieved by testing and ARV treating. Longitudinal analysis of 42 seroconverters revealed that 33% (95% CI: 20%–50%) of individuals maintain high HIV-1 RNA levels for at least 180 days post seroconversion (p/s) and the median duration of high viral load period was 350 (269; 428) days p/s. We found that it would be possible to identify all HIV-infected individuals with viral load ≥50,000 (4.7 log10) copies/ml using repeated six-month-interval HIV testing. Assuming individuals with high viral load initiate cART after being identified, the period of high transmissibility due to high viral load can potentially be reduced by 77% (95% CI: 71%–82%). Therefore, if HIV-infected individuals maintaining high levels of plasma HIV-1 RNA for extended period of time contribute disproportionally to HIV transmission, a modified “test-and-treat” strategy targeting such individuals by repeated HIV testing (followed by initiation of cART) might be a useful public health strategy for mitigating the HIV epidemic in some communities

individual participant data meta-analysis of randomised trials study protocol

Introduction Parenteral anticoagulants may improve outcomes in patients with cancer by reducing risk of venous thromboembolic disease and through a direct antitumour effect. Study-level systematic reviews indicate a reduction in venous thromboembolism and provide moderate confidence that a small survival benefit exists. It remains unclear if any patient subgroups experience potential benefits. Methods and analysis First, we will perform a comprehensive systematic search of MEDLINE, EMBASE and The Cochrane Library, hand search scientific conference abstracts and check clinical trials registries for randomised control trials of participants with solid cancers who are administered parenteral anticoagulants. We anticipate identifying at least 15 trials, exceeding 9000 participants. Second, we will perform an individual participant data meta-analysis to explore the magnitude of survival benefit and address whether subgroups of patients are more likely to benefit from parenteral anticoagulants. All analyses will follow the intention-to- treat principle. For our primary outcome, mortality, we will use multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We will adjust analysis for important prognostic characteristics. To investigate whether intervention effects vary by predefined subgroups of patients, we will test interaction terms in the statistical model. Furthermore, we will develop a risk-prediction model for venous thromboembolism, with a focus on control patients of randomised trials. Ethics and dissemination Aside from maintaining participant anonymity, there are no major ethical concerns. This will be the first individual participant data meta-analysis addressing heparin use among patients with cancer and will directly influence recommendations in clinical practice guidelines. Major cancer guideline development organisations will use eventual results to inform their guideline recommendations. Several knowledge users will disseminate results through presentations at clinical rounds as well as national and international conferences. We will prepare an evidence brief and facilitate dialogue to engage policymakers and stakeholders in acting on findings. Trial registration number PROSPERO CRD4201300352

A useful savagery: The invention of violence in nineteenth-century England

‘A Useful Savagery: The Invention of Violence in Nineteenth-Century England’ considers a particular configuration of attitudes toward violence that emerged in the early decades of the nineteenth century. As part of a longer-term process of emerging ‘sensibilities,’ violence was, seemingly paradoxically, ‘invented’ as a social issue while concurrently relocated in the ‘civilised’ imagination as an anti-social feature mainly of ‘savage’ working-class life. The dominant way this discourse evolved was through the creation of a narrative that defined ‘civilisation’ in opposition to the presumed ‘savagery’ of the working classes. Although the refined classes were often distanced from the physical experience of violence, concern with violence and brutality became significant parts of social commentary aimed at a middle-class readership. While stridently redefining themselves in opposition to ‘brutality,’ one of the purposes of this literature was to create a new middle class and justify the expansion of state power. By the closing decades of the nineteenth century, as the working classes adopted tenets of Victorian respectability, a proliferating number of social and psychological ‘others’ were identified against which ‘civilised’ thought could define itself