The ARTEMIS simulations: stellar haloes of Milky Way-mass galaxies

We introduce the Assembly of high-ResoluTion Eagle-simulations of MIlky Way-type galaxieS (ARTEMIS) simulations, a new set of 42 zoomed-in, high-resolution (baryon particle mass of ≈2×104M⊙h−1⁠), hydrodynamical simulations of galaxies residing in haloes of Milky Way mass, simulated with the EAGLE galaxy formation code with re-calibrated stellar feedback. In this study, we analyse the structure of stellar haloes, specifically the mass density, surface brightness, metallicity, colour, and age radial profiles, finding generally very good agreement with recent observations of local galaxies. The stellar density profiles are well fitted by broken power laws, with inner slopes of ≈−3, outer slopes of ≈−4, and break radii that are typically ≈20–40 kpc. The break radii generally mark the transition between in situ formation and accretion-driven formation of the halo. The metallicity, colour, and age profiles show mild large-scale gradients, particularly when spherically averaged or viewed along the major axes. Along the minor axes, however, the profiles are nearly flat, in agreement with observations. Overall, the structural properties can be understood by two factors: that in situ stars dominate the inner regions and that they reside in a spatially flattened distribution that is aligned with the disc. Observations targeting both the major and minor axes of galaxies are thus required to obtain a complete picture of stellar haloes

Informing dark matter direct detection limits with the ARTEMIS simulations

Dark matter (DM) direct detection experiments aim to place constraints on the DM--nucleon scattering cross-section and the DM particle mass. These constraints depend sensitively on the assumed local DM density and velocity distribution function. While astrophysical observations can inform the former (in a model-dependent way), the latter is not directly accessible with observations. Here we use the high-resolution ARTEMIS cosmological hydrodynamical simulation suite of 42 Milky Way-mass halos to explore the spatial and kinematical distributions of the DM in the solar neighbourhood, and we examine how these quantities are influenced by substructures, baryons, the presence of dark discs, as well as general halo-to-halo scatter (cosmic variance). We also explore the accuracy of the standard Maxwellian approach for modelling the velocity distribution function. We find significant halo-to-halo scatter in the density and velocity functions which, if propagated through the standard halo model for predicting the DM detection limits, implies a significant scatter about the typically quoted limit. We also show that, in general, the Maxwellian approximation works relatively well for simulations that include the important gravitational effects of baryons, but is less accurate for collisionless (DM-only) simulations. Given the significant halo-to-halo scatter in quantities relevant for DM direct detection, we advocate propagating this source of uncertainty through in order to derive conservative DM detection limits

Evolutionary Patterns of the Mitochondrial Genome in Metazoa: Exploring the Role of Mutation and Selection in Mitochondrial Protein–Coding Genes

The mitochondrial genome is a fundamental component of the eukaryotic domain of life, encoding for several important subunits of the respiratory chain, the main energy production system in cells. The processes by means of which mitochondrial DNA (mtDNA) replicates, expresses itself and evolves have been explored over the years, although various aspects are still debated. In this review, we present several key points in modern research on the role of evolutionary forces in affecting mitochondrial genomes in Metazoa. In particular, we assemble the main data on their evolution, describing the contributions of mutational pressure, purifying, and adaptive selection, and how they are related. We also provide data on the evolutionary fate of the mitochondrial synonymous variation, related to the nonsynonymous variation, in comparison with the pattern detected in the nucleus

The Relative Influence of Competition and Prey Defenses on the Phenotypic Structure of Insectivorous Bat Ensembles in Southern Africa

Deterministic filters such as competition and prey defences should have a strong influence on the community structure of animals such as insectivorous bats that have life histories characterized by low fecundity, low predation risk, long life expectancy, and stable populations. We investigated the relative influence of these two deterministic filters on the phenotypic structure of insectivorous bat ensembles in southern Africa. We used null models to simulate the random phenotypic patterns expected in the absence of competition or prey defences and analysed the deviations of the observed phenotypic pattern from these expected random patterns. The phenotypic structure at local scales exhibited non-random patterns consistent with both competition and prey defense hypotheses. There was evidence that competition influenced body size distribution across ensembles. Competition also influenced wing and echolocation patterns in ensembles and in functional foraging groups with high species richness or abundance. At the same time, prey defense filters influenced echolocation patterns in two species-poor ensembles. Non-random patterns remained evident even after we removed the influence of body size from wing morphology and echolocation parameters taking phylogeny into account. However, abiotic filters such as geographic distribution ranges of small and large-bodied species, extinction risk, and the physics of flight and sound probably also interacted with biotic filters at local and/or regional scales to influence the community structure of sympatric bats in southern Africa. Future studies should investigate alternative parameters that define bat community structure such as diet and abundance to better determine the influence of competition and prey defences on the structure of insectivorous bat ensembles in southern Africa

Perfil fenotípico e susceptibilidade antimicrobiana de Streptococcus equi isolados de equinos da região Sul do Brasil

As características fenotípicas [morfológicas, bioquímicas, susceptibilidade aos antimicrobianos, índice de resistência múltipla aos antimicrobianos (IRMA), concentração inibitória mínima (CIM) e concentração bactericida mínima (CBM) da benzilpenicilina] de 38 isolados de Streptococcus equi oriundos de amostras clínicas de animais com adenite equina foram alvo deste estudo. A fenotipia demonstrou três padrões de colônias, três biotipos de fermentação de carboidratos e variação de 0 a 0,4 no IRMA. Todos os isolados de S. equi demonstraram sensibilidade à penicilina, tanto pelo método de disco difusão quanto pelo método de microdiluição. A CIM e CBM média de benzilpenicilina foi de 0,0095μg/mL e 0,0267μg/mL para S. equi subesp. equi e de 0,0128μg/mL e 0,0380μg/mL para S. equi subesp. zooepidemicus. Os valores de CIM e CBM diferiram entre as subespécies (p<0,05). O diâmetro do halo de inibição de penicilina demonstrou relação com a CIM (ì=0,03638 - 0,00072x) para S. equi subesp. equi. Também foi demonstrada relação entre o diâmetro do halo de inibição de penicilina com a CBM para S. equi subesp. equi (ì=0,10931- 0,00223x). Entretanto para as amostras de S. equi subesp. zooepidemicus esta relação somente foi verificada para a CBM (ì=0,1322 - 0,00271x). A CIM de benzilpenicilina frente às amostras isoladas da região Central, Planalto e Sul do estado do Rio Grande do Sul foram estatisticamente semelhantes, mas diferiram do isolado do estado do Paraná, sugerindo o caráter atípico desta cepa. Todos os isolados de S. equi são sensíveis à penicilina e sulfazotrim, confirmando a eleição destes antimicrobianos para o tratamento das infecções por este agente na clínica veterinária. Os resultados obtidos não dispensam a utilização prudente dos antimicrobianos

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. Findings Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants’ systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups. Interpretation Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultraacute prehospital setting. Funding British Heart Foundation

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population