The XMM Cluster Survey: The Stellar Mass Assembly of Fossil Galaxies

This paper presents both the result of a search for fossil systems (FSs) within the XMM Cluster Survey and the Sloan Digital Sky Survey and the results of a study of the stellar mass assembly and stellar populations of their fossil galaxies. In total, 17 groups and clusters are identified at z < 0.25 with large magnitude gaps between the first and fourth brightest galaxies. All the information necessary to classify these systems as fossils is provided. For both groups and clusters, the total and fractional luminosity of the brightest galaxy is positively correlated with the magnitude gap. The brightest galaxies in FSs (called fossil galaxies) have stellar populations and star formation histories which are similar to normal brightest cluster galaxies (BCGs). However, at fixed group/cluster mass, the stellar masses of the fossil galaxies are larger compared to normal BCGs, a fact that holds true over a wide range of group/cluster masses. Moreover, the fossil galaxies are found to contain a significant fraction of the total optical luminosity of the group/cluster within 0.5R200, as much as 85%, compared to the non-fossils, which can have as little as 10%. Our results suggest that FSs formed early and in the highest density regions of the universe and that fossil galaxies represent the end products of galaxy mergers in groups and clusters. The online FS catalog can be found at http://www.astro.ljmu.ac.uk/~xcs/Harrison2012/XCSFSCat.html.Comment: 30 pages, 50 figures. ApJ published version, online FS catalog added: http://www.astro.ljmu.ac.uk/~xcs/Harrison2012/XCSFSCat.htm

The central slope of dark matter cores in dwarf galaxies: Simulations vs. THINGS

We make a direct comparison of the derived dark matter (DM) distributions between hydrodynamical simulations of dwarf galaxies assuming a LCDM cosmology and the observed dwarf galaxies sample from the THINGS survey in terms of (1) the rotation curve shape and (2) the logarithmic inner density slope alpha of mass density profiles. The simulations, which include the effect of baryonic feedback processes, such as gas cooling, star formation, cosmic UV background heating and most importantly physically motivated gas outflows driven by supernovae (SNe), form bulgeless galaxies with DM cores. We show that the stellar and baryonic mass is similar to that inferred from photometric and kinematic methods for galaxies of similar circular velocity. Analyzing the simulations in exactly the same way as the observational sample allows us to address directly the so-called "cusp/core" problem in the LCDM model. We show that the rotation curves of the simulated dwarf galaxies rise less steeply than CDM rotation curves and are consistent with those of the THINGS dwarf galaxies. The mean value of the logarithmic inner density slopes alpha of the simulated galaxies' dark matter density profiles is ~ -0.4 +- 0.1, which shows good agreement with \alpha = -0.29 +- 0.07 of the THINGS dwarf galaxies. The effect of non-circular motions is not significant enough to affect the results. This confirms that the baryonic feedback processes included in the simulations are efficiently able to make the initial cusps with \alpha ~ -1.0 to -1.5 predicted by dark-matter-only simulations shallower, and induce DM halos with a central mass distribution similar to that observed in nearby dwarf galaxies.Comment: 13 pages, 7 figures; Accepted for publication in AJ; minor correction

Short-term safety outcomes of mastectomy and immediate implant-based breast reconstruction with and without mesh (iBRA): a multicentre, prospective cohort study

Background Use of biological or synthetic mesh might improve outcomes of immediate implant-based breast reconstruction—breast reconstruction with implants or expanders at the time of mastectomy—but there is a lack of high-quality evidence to support the safety or effectiveness of the technique. We aimed to establish the short-term safety of immediate implant-based breast reconstruction performed with and without mesh, to inform the feasibility of undertaking a future randomised clinical trial comparing different breast reconstruction techniques. Methods In this prospective, multicentre cohort study, we consecutively recruited women aged 16 years or older who had any type of immediate implant-based breast reconstruction for malignancy or risk reduction, with any technique, at 81 participating breast and plastic surgical units in the UK. Data about patient demographics and operative, oncological, and complication details were collected before and after surgery. Outcomes of interest were implant loss (defined as unplanned removal of the expander or implant), infection requiring treatment with antibiotics or surgery, unplanned return to theatre, and unplanned re-admission to hospital for complications of reconstructive surgery, up to 3 months after reconstruction and assessed by clinical review or patient self-report. Follow-up is complete. The study is registered with the ISRCTN Registry, number ISRCTN37664281. Findings Between Feb 1, 2014, and June 30, 2016, 2108 patients had 2655 mastectomies with immediate implant-based breast reconstruction at 81 units across the UK. 1650 (78%) patients had planned single-stage reconstructions (including 12 patients who had a different technique per breast). 1376 (65%) patients had reconstruction with biological (1133 [54%]) or synthetic (243 [12%]) mesh, 181 (9%) had non-mesh submuscular or subfascial implants, 440 (21%) had dermal sling implants, 42 (2%) had pre-pectoral implants, and 79 (4%) had other or a combination of implants. 3-month outcome data were available for 2081 (99%) patients. Of these patients, 182 (9%, 95% CI 8–10) experienced implant loss, 372 (18%, 16–20) required re-admission to hospital, and 370 (18%, 16–20) required return to theatre for complications within 3 months of their initial surgery. 522 (25%, 95% CI 23–27) patients required treatment for an infection. The rates of all of these complications are higher than those in the National Quality Standards (<5% for re-operation, re-admission, and implant loss, and <10% for infection). Interpretation Complications after immediate implant-based breast reconstruction are higher than recommended by national standards. A randomised clinical trial is needed to establish the optimal approach to immediate implant-based breast reconstruction

Maintaining independence in individuals with dementia at home after a fall:a protocol for the UK pilot cluster randomised controlled trial MAINTAIN

Introduction: Individuals with dementia face an increased risk of falls. Falls can cause a decline in the individual’s overall functionality. All types of falls, including those that do not result in injury, can lead to psychosocial consequences, such as diminished confidence and a fear of falling. Projections indicate a rising trend in dementia diagnoses, implying an increase in fall incidents. Yet, there is a lack of evidence to support interventions for people living with dementia who have fallen. Our objective is to test the feasibility of a falls intervention trial for people with dementia. Method and analysis: This is a UK-based two-arm pilot cluster randomised controlled trial. In this study, six collaborating sites, which form the clusters, will be randomly allocated to either the intervention arm or the control arm (receiving treatment as usual) at a 1:1 ratio. During the 6 month recruitment phase, each cluster will enrol 10 dyads, comprising 10 individuals with dementia and their respective carers, leading to a total sample size of 60 dyads. The primary outcomes are the feasibility parameters for a full trial (ie, percentage consented, follow-up rate and cost framework). Secondary outcomes include activities of daily living, quality of life, fall efficacy, mobility, goal attainment, cognitive status, occurrence of falls, carer burden and healthcare service utilisation. Outcome measures will be collected at baseline and 28 weeks, with an additional assessment scheduled at 12 weeks for the healthcare service utilisation questionnaire. An embedded process evaluation, consisting of interviews and observations with participants and healthcare professionals, will explore how the intervention operates and the fidelity of study processes. Ethics and dissemination: The study was approved by the NHS and local authority research governance and research ethics committees (NHS REC reference: 23/WA/0126). The results will be shared at meetings and conferences and will be published in peer-reviewed journals. Trial registration number: ISRCTN16413728

Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA

Tumor-associated peptide–human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface–expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these targets using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions of natural TCRs (e.g., immune-mobilizing monoclonal T cell receptors against cancer [ImmTAC] molecules), whereas the second harnesses an antibody-based format (TCR-mimic antibodies). For both classes of reagent, target specificity is vital, considering the vast universe of potential pHLA molecules that can be presented on healthy cells. Here, we made use of structural, biochemical, and computational approaches to investigate the molecular rules underpinning the reactivity patterns of pHLA-targeting bispecifics. We demonstrate that affinity-enhanced TCRs engage pHLA using a comparatively broad and balanced energetic footprint, with interactions distributed over several HLA and peptide side chains. As ImmTAC molecules, these TCRs also retained a greater degree of pHLA selectivity, with less off-target activity in cellular assays. Conversely, TCR-mimic antibodies tended to exhibit binding modes focused more toward hot spots on the HLA surface and exhibited a greater degree of crossreactivity. Our findings extend our understanding of the basic principles that underpin pHLA selectivity and exemplify a number of molecular approaches that can be used to probe the specificity of pHLA-targeting molecules, aiding the development of future reagents

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

Measurements of observables sensitive to colour reconnection in ¯ events with the ATLAS detector at √ = 13 TeV

A measurement of observables sensitive to effects of colour reconnection in top-quark pair-production events is presented using 139 fb−1 of 13 TeV proton–proton collision data collected by the ATLAS detector at the LHC. Events are selected by requiring exactly one isolated electron and one isolated muon with opposite charge and two or three jets, where exactly two jets are required to be b-tagged. For the selected events, measurements are presented for the charged-particle multiplicity, the scalar sum of the transverse momenta of the charged particles, and the same scalar sum in bins of charged-particle multiplicity. These observables are unfolded to the stable-particle level, thereby correcting for migration effects due to finite detector resolution, acceptance and efficiency effects. The particle-level measurements are compared with different colour reconnection models in Monte Carlo generators. These measurements disfavour some of the colour reconnection models and provide inputs to future optimisation of the parameters in Monte Carlo generators

ATLAS flavour-tagging algorithms for the LHC Run 2 pp collision dataset

The flavour-tagging algorithms developed by the ATLAS Collaboration and used to analyse its dataset of √s = 13 TeV pp collisions from Run 2 of the Large Hadron Collider are presented. These new tagging algorithms are based on recurrent and deep neural networks, and their performance is evaluated in simulated collision events. These developments yield considerable improvements over previous jet-flavour identification strategies. At the 77% b-jet identification efficiency operating point, light-jet (charm-jet) rejection factors of 170 (5) are achieved in a sample of simulated Standard Model tt¯ events; similarly, at a c-jet identification efficiency of 30%, a light-jet (b-jet) rejection factor of 70 (9) is obtained

New Horizons in the use of routine data for ageing research

The past three decades have seen a steady increase in the availability of routinely collected health and social care data and the processing power to analyse it. These developments represent a major opportunity for ageing research, especially with the integration of different datasets across traditional boundaries of health and social care, for prognostic research and novel evaluations of interventions with representative populations of older people. However, there are considerable challenges in using routine data at the level of coding, data analysis and in the application of findings to everyday care. New Horizons in applying routine data to investigate novel questions in ageing research require a collaborative approach between clinicians, data scientists, biostatisticians, epidemiologists and trial methodologists. This requires building capacity for the next generation of research leaders in this important area. There is a need to develop consensus code lists and standardised, validated algorithms for common conditions and outcomes that are relevant for older people to maximise the potential of routine data research in this group. Lastly, we must help drive the application of routine data to improve the care of older people, through the development of novel methods for evaluation of interventions using routine data infrastructure. We believe that harnessing routine data can help address knowledge gaps for older people living with multiple conditions and frailty, and design interventions and pathways of care to address the complex health issues we face in caring for older people

Evaluation of the guide to action care home fall prevention programme in care homes for older people: A multi-centre, single blinded, cluster randomised controlled trial (FINCH)

BackgroundFalls in care home residents are common, unpleasant, costly and difficult to prevent. Trial DesignThe objective was to evaluate the clinical and cost effectiveness of the Guide to Action for Falls Prevention Care Homes, GtACH) in which care home staff were trained and supported in the systematic use of a multi-domain decision support tool and identify issues affecting subsequent implementation. A two-arm parallel design, multi-centre, cluster randomised controlled trial of the GtACH programme and usual falls prevention in older care home residents was conducted with embedded process evaluation and economic evaluation. MethodThe study was conducted in care homes from ten UK sites. The primary trial outcome was the rate of falls per resident participant occurring during the 90-day period between 91 days and 180 days post-randomisation. The primary outcome for the cost effectiveness analysis was the cost per fall averted and for the cost utility analysis was the incremental cost per QALY. Secondary outcomes included the rate of falls over days 0-90 and 181-360 post randomisation, activity levels, dependency, and fractures. Care homes were randomised on a 1:1 basis to the GtACH programme or usual care, via a secure web-based randomisation service. Research assistants (RAs), resident participants and staff informants were blind to allocation at recruitment. RAs were blind to allocation at follow up. Data from NHS Digital were extracted blindly. The number of falls per resident was compared between groups using a negative binomial regression model (GEE).Results84 care homes were randomised, 39 to GtACH and 45 to usual care. 1657 residents consented and provided baseline measures, mean age 85 years, 32% men. GtACH training was delivered to 1051 staff (71% of eligible staff) over 146 group sessions. Primary RCT outcome data were available for 630 of the GtACH participants and 712 usual care participants. The primary RCT outcome result showed an unadjusted Incidence Rate Ratio (IRR) of 0.57 (95% CI 0.45-0.71, p<0.01) in favour of the GtACH programme. Fall rates were also lower in the GtACH group in the period 0-90 days, but there were no other differences between groups in the secondary outcomes. Care home staff valued the training, the systematic strategies and the specialist peer support, but there was limited incorporation of the GtACH documentation into routine care home practice. No adverse events were recorded. The incremental cost per DEMQoL-based QALY was £20,889.42 and £4,543.69 per EQ-5D based QALY. Mean falls were 1.889 (sd 3.662) in the GtACH arm and 2.747 (sd 7.414) in the usual care arm. Therefore, 0.858 falls were averted. The base case incremental cost per fall averted was £190.62ConclusionThe GtACH programme significantly reduced the rate of falls in the study care homes, without restricting residents’ activity levels or increasing their dependency and was cost effective at current thresholds in the UK NHS. Widespread implementation of the programme is justified. Trial registrationTrial registration number: ISRCTN34353836. Protocol V6 14 November 2017Funding DetailsThe National Institute for Health Research (NIHR) HTA programm