Seen and unseen tidal caustics in the Andromeda galaxy

Indirect detection of high-energy particles from dark matter interactions is a promising avenue for learning more about dark matter, but is hampered by the frequent coincidence of high-energy astrophysical sources of such particles with putative high-density regions of dark matter. We calculate the boost factor and gamma-ray flux from dark matter associated with two shell-like caustics of luminous tidal debris recently discovered around the Andromeda galaxy, under the assumption that dark matter is its own supersymmetric antiparticle. These shell features could be a good candidate for indirect detection of dark matter via gamma rays because they are located far from the primary confusion sources at the galaxy's center, and because the shapes of the shells indicate that most of the mass has piled up near apocenter. Using a numerical estimator specifically calibrated to estimate densities in N-body representations with sharp features and a previously determined N-body model of the shells, we find that the largest boost factors do occur in the shells but are only a few percent. We also find that the gamma-ray flux is an order of magnitude too low to be detected with Fermi for likely dark matter parameters, and about 2 orders of magnitude less than the signal that would have come from the dwarf galaxy that produces the shells in the N-body model. We further show that the radial density profiles and relative radial spacing of the shells, in either dark or luminous matter, is relatively insensitive to the details of the potential of the host galaxy but depends in a predictable way on the velocity dispersion of the progenitor galaxy.Comment: ApJ accepte

The relationship between EQ-5D, HAQ and pain in patients with rheumatoid arthritis: further validation and development of the limited dependent variable, mixture model approach

Objective: To provide robust estimates of EQ-5D as a function of the Health Assessment Questionnaire (HAQ) and pain in patients with rheumatoid arthritis. Method: Repeated observations of patients diagnosed with RA in a US observational cohort (n=100,398 observations) who provided data on HAQ, pain on a visual analogue scale and the EQ-5D questionnaire. We use a bespoke mixture modelling approach to appropriately reflect the characteristics of the EQ-5D instrument and compare this to results from linear regression. Results: The addition of pain alongside HAQ as an explanatory variable substantially improves explanatory power. The preferred model is a four component mixture. Unlike the linear regression it exhibits very good fit to the data, does not suffer from problems of bias or predict values outside the feasible range. Conclusions: It is appropriate to model the relationship between HAQ and EQ-5D but only if suitable statistical methods are applied. Linear models underestimate the QALY benefits, and therefore the cost effectiveness, of therapies. The bespoke mixture model approach outlined here overcomes this problem. The addition of pain as an explanatory variable greatly improves the estimates

Region-Wide Ecological Responses of Arid Wyoming Big Sagebrush Communities to Fuel Treatments

If arid sagebrush ecosystems lack resilience to disturbances or resistance to annual invasives, then alternative successional states dominated by annual invasives, especially cheatgrass (Bromus tectorum L.), are likely after fuel treatments. We identified six Wyoming big sagebrush (Artemisia tridentata ssp. wyomingensis Beetle & Young) locations (152–381 mm precipitation) that we believed had sufficient resilience and resistance for recovery. We examined impacts of woody fuel reduction (fire, mowing, the herbicide tebuthiuron, and untreated controls, all with and without the herbicide imazapic) on short-term dominance of plant groups and on important land health parameters with the use of analysis of variance (ANOVA). Fire and mowing reduced woody biomass at least 85% for 3 yr, but herbaceous fuels were reduced only by fire (72%) and only in the first year. Herbaceous fuels produced at least 36% more biomass with mowing than untreated areas during posttreatment years. Imazapic only reduced herbaceous biomass after fires (34%). Tebuthiuron never affected herbaceous biomass. Perennial tall grass cover was reduced by 59% relative to untreated controls in the first year after fire, but it recovered by the second year. Cover of all remaining herbaceous groups was not changed by woody fuel treatments. Only imazapic reduced significantly herbaceous cover. Cheatgrass cover was reduced at least 63% with imazapic for 3 yr. Imazapic reduced annual forb cover by at least 45%, and unexpectedly, perennial grass cover by 49% (combination of tall grasses and Sandberg bluegrass [Poa secunda J. Presl.]). Fire reduced density of Sandberg bluegrass between 40% and 58%, decreased lichen and moss cover between 69% and 80%, and consequently increased bare ground between 21% and 34% and proportion of gaps among perennial plants &spigt; 2 m (at least 28% during the 3 yr). Fire, mowing, and imazapic may be effective in reducing fuels for 3 yr, but each has potentially undesirable consequences on plant communities

A Computation in a Cellular Automaton Collider Rule 110

A cellular automaton collider is a finite state machine build of rings of one-dimensional cellular automata. We show how a computation can be performed on the collider by exploiting interactions between gliders (particles, localisations). The constructions proposed are based on universality of elementary cellular automaton rule 110, cyclic tag systems, supercolliders, and computing on rings.Comment: 39 pages, 32 figures, 3 table

Visión general de las percepciones regionales sobre el rol de la educación superior para el desarrollo humano y social

Nuestro informe ha estudiado en su Parte I temas globales seleccionados acerca del rol de la educación superior para el desarrollo humano y social. Este trabajo es una síntesis de las perspectivas regionales -África Subsahariana, Estados Árabes, Asia y el Pacífico, Europa, América del Norte y América Latina y el Caribe- acerca del rol de la educación superior para el desarrollo humano y social basado en la contribución de los autores en cinco áreas claves: una de ellas es el estado de la educacion superior en cada región desde la celebración de la Conferencia Mundial sobre Educación Superior (CMES, 1998); y otra de las cuatro áreas clave se refiere a los posibles roles futuros, estrategias y acciones de la educación superior para promover el desarrollo humano y social.Peer Reviewe

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Background: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. Methods: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Findings: Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. Interpretation: Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. Funding: Bayer and Janssen

Ring-fused 2-pyridones effective against multidrug-resistant Gram-positive pathogens and synergistic with standard-of-care antibiotics

The alarming rise of multidrug-resistant Gram-positive bacteria has precipitated a healthcare crisis, necessitating the development of new antimicrobial therapies. Here we describe a new class of antibiotics based on a ring-fused 2-pyridone backbone, which are active against vancomycin-resistant enterococci (VRE), a serious threat as classified by the Centers for Disease Control and Prevention, and other multidrug-resistant Gram-positive bacteria. Ring-fused 2-pyridone antibiotics have bacteriostatic activity against actively dividing exponential phase enterococcal cells and bactericidal activity against nondividing stationary phase enterococcal cells. The molecular mechanism of drug-induced killing of stationary phase cells mimics aspects of fratricide observed in enterococcal biofilms, where both are mediated by the Atn autolysin and the GelE protease. In addition, combinations of sublethal concentrations of ring-fused 2-pyridones and standard-of-care antibiotics, such as vancomycin, were found to synergize to kill clinical strains of VRE. Furthermore, a broad range of antibiotic resistant Gram-positive pathogens, including those responsible for the increasing incidence of antibiotic resistant healthcare-associated infections, are susceptible to this new class of 2-pyridone antibiotics. Given the broad antibacterial activities of ring-fused 2-pyridone compounds against Gram-positive (GmP) bacteria we term these compounds GmPcides, which hold promise in combating the rising tide of antibiotic resistant Gram-positive pathogens

Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

This corrects the article DOI: 10.1038/sdata.2017.179

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Background: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. Methods: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Findings: Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. Interpretation: Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. Funding: Bayer and Janssen