Glutathione peroxidase in acute coronary syndromes

Glutathione peroxidase (GPx) and superoxide dismutase (SOD) are among the primary antioxidant enzymes that scavenge reactive oxygen species in the blood (ROS), thereby protecting against high levels of oxidative stress. The consequences of oxidative stress include cellular injury and tissue damage. High levels of oxidative stress have been implicated in the pathogenesis of acute coronary syndromes (ACS), however large clinical trials involving dietary antioxidant supplements have not shown a reduction in the rate of major adverse cardiovascular events (MACE). In a cohort of 262 ACS patients we examined the relationship between GPx activity, SOD activity and MACE. Patients with MACE were found to have significantly lower levels of GPx activity than those without MACE, whereas SOD activity did not differ between the groups. Furthermore, dividing the patients into quartiles corresponding to levels of GPx activity demonstrated significantly higher rates of MACE in the lower quartile of GPx activity compared to the highest quartile. Previous studies have demonstrated that deficiencies in GPx activity are associated with vascular dysfunction and platelet-dependent thrombosis, leading to the hypothesis that low levels of GPx activity would be associated with increased levels of platelet reactivity. In 51 ACS patients we did not observe a significant relationship between these two parameters, however we did demonstrate that increasing levels of GPx activity was associated with lower levels of ROS. ROS measures were based on the response of the platelets to addition of exogenous nitric oxide. Such an inverse relationship between GPx activity and levels of ROS is consistent with the view that GPx activity may play an important role in an ACS by reducing ROS-mediated damage, thereby protecting against MACE. We examined levels of GPx activity, protein concentration and mRNA expression across populations of ACS patients, stable coronary disease patients and healthy subjects. Cardiovascular risk factors thought to influence levels of GPx activity were controlled for in all three cohorts. These studies demonstrated that GPx activity, protein and mRNA levels were significantly elevated in the ACS patients compared to the stable coronary disease patients and healthy subjects. Oxidised low-density lipoprotein (oxLDL), a widely used marker of oxidative stress, was also significantly elevated in the ACS patients compared to the other two cohorts. In a study examining the temporal changes in GPx activity in the acute phase of an ACS, GPx activity was found to be highly dynamic, with no consistent single time point that identified when peak activity occurred. In the majority of patients, levels of oxLDL were found to peak prior to, or at the same time, as peak GPx activity, suggesting that GPx activity was modulated by changes in oxidative stress. In conclusion, the elevated levels of GPx activity observed in ACS patients were found to be highly dynamic throughout an ACS event. However those with lower levels of GPx activity have an increased risk of adverse clinical outcomes that may be due to an inadequate defence against levels of ROS. Whether these patients can be accurately identified and targeted with an appropriate therapeutic intervention warrants further investigation

Barriers and facilitators to asthma self-management in adolescents:a systematic review of qualitative and quantitative studies

BACKGROUND: Many adolescents have poor asthma control and impaired quality of life despite the availability of modern pharmacotherapy. Research suggests that poor adherence to treatment and limited engagement in self-management could be contributing factors. OBJECTIVE: To conduct a systematic review of the barriers and facilitators to self-management of asthma reported by adolescents using a narrative synthesis approach to integrate the findings. DESIGN: MEDLINE, EMBASE, CINAHL, and PsycINFO were searched for all types of study design. Full papers were retrieved for study abstracts that included data from participants aged 12-18 years referring to barriers or facilitators of asthma self-management behaviors. RESULTS: Sixteen studies (5 quantitative and 11 qualitative) underwent data extraction, quality appraisal, and thematic analysis. Six key themes were generated that encompassed barriers and/or facilitators to self-management of asthma in adolescents: Knowledge, Lifestyle, Beliefs and Attitudes, Relationships, Intrapersonal Characteristics, and Communication. CONCLUSIONS: There is a pressing need to prepare adolescents for self-management, using age-appropriate strategies that draw on the evidence we have synthesized. Current clinical practice should focus on ensuring adolescents have the correct knowledge, beliefs, and positive attitude to self-manage their illness. This needs to be delivered in a supportive environment that facilitates two-way communication, fosters adolescents' self-efficacy to manage their disease, and considers the wider social influences that impinge on self-management. Pediatr Pulmonol. 2016; 9999:XX-XX. © 2016 Wiley Periodicals, Inc

A protocol for a systematic review and meta-analysis to identify measures of breakthrough pain and evaluate their psychometric properties.

INTRODUCTION: Breakthrough pain is common in children and adults with cancer and other conditions, including those approaching end-of-life, although it is often poorly managed, possibly partly due to a lack of validated assessment tools. This review aims to (1) identify all available instruments measuring breakthrough pain in infants, children, adolescents or adults and (2) critically appraise, compare and summarise the quality of the psychometric properties of the identified instruments using COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. METHODS AND ANALYSIS: Two searches will be carried out between October 2019 and January 2020, one for each aim of the review. The Cochrane Library, International Prospective Register of Systematic Reviews, Embase, Cumulative Index of Nursing and Allied Health Literature, Medical Literature Analysis and Retrieval System Online (MEDLINE), PsycINFO, Web of Science Core Collection, Google Scholar, the ProQuest Dissertations & Theses Database, Evidence Search and OpenGrey databases will be searched from database inception until the date the search is conducted. Reference lists of eligible articles will be screened and authors in the field contacted. For search 1, articles will be screened by two reviewers by abstract, and full-text where necessary, to identify if a breakthrough pain assessment was used. Search 2 will then be conducted to identify studies evaluating measurement properties of these assessments. Two reviewers will screen articles from search 2 by title and abstract. All potentially relevant studies will be screened by full text by both reviewers. For search 2, data will be extracted in parallel with the quality assessment process, as recommended by COSMIN. Two reviewers will assess methodological quality using the COSMIN Risk of Bias checklist and the COSMIN updated criteria for good measurement properties. Findings will be summarised and, if possible, data will be pooled using meta-analysis. The quality of the evidence will be graded and summarised using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines. ETHICS AND DISSEMINATION: Results of this review will be submitted for publication in a peer review journal and presented at conferences. PROSPERO REGISTRATION NUMBER: CRD42019155583

Modelling the shapes of the largest gravitationally bound objects

We combine the physics of the ellipsoidal collapse model with the excursion set theory to study the shapes of dark matter halos. In particular, we develop an analytic approximation to the nonlinear evolution that is more accurate than the Zeldovich approximation; we introduce a planar representation of halo axis ratios, which allows a concise and intuitive description of the dynamics of collapsing regions and allows one to relate the final shape of a halo to its initial shape; we provide simple physical explanations for some empirical fitting formulae obtained from numerical studies. Comparison with simulations is challenging, as there is no agreement about how to define a non-spherical gravitationally bound object. Nevertheless, we find that our model matches the conditional minor-to-intermediate axis ratio distribution rather well, although it disagrees with the numerical results in reproducing the minor-to-major axis ratio distribution. In particular, the mass dependence of the minor-to-major axis distribution appears to be the opposite to what is found in many previous numerical studies, where low-mass halos are preferentially more spherical than high-mass halos. In our model, the high-mass halos are predicted to be more spherical, consistent with results based on a more recent and elaborate halo finding algorithm, and with observations of the mass dependence of the shapes of early-type galaxies. We suggest that some of the disagreement with some previous numerical studies may be alleviated if we consider only isolated halos.Comment: 15 pages, 8 figures. New appendix added, extended discussion. Matches version accepted by MNRA

What Ecological Factors Shape Species-Area Curves in Neutral Models?

Understanding factors that shape biodiversity and species coexistence across scales is of utmost importance in ecology, both theoretically and for conservation policies. Species-area relationships (SARs), measuring how the number of observed species increases upon enlarging the sampled area, constitute a convenient tool for quantifying the spatial structure of biodiversity. While general features of species-area curves are quite universal across ecosystems, some quantitative aspects can change significantly. Several attempts have been made to link these variations to ecological forces. Within the framework of spatially explicit neutral models, here we scrutinize the effect of varying the local population size (i.e. the number of individuals per site) and the level of habitat saturation (allowing for empty sites). We conclude that species-area curves become shallower when the local population size increases, while habitat saturation, unless strongly violated, plays a marginal role. Our findings provide a plausible explanation of why SARs for microorganisms are flatter than those for larger organisms

Dynamics of Disks and Warps

This chapter reviews theoretical work on the stellar dynamics of galaxy disks. All the known collective global instabilities are identified, and their mechanisms described in terms of local wave mechanics. A detailed discussion of warps and other bending waves is also given. The structure of bars in galaxies, and their effect on galaxy evolution, is now reasonably well understood, but there is still no convincing explanation for their origin and frequency. Spiral patterns have long presented a special challenge, and ideas and recent developments are reviewed. Other topics include scattering of disk stars and the survival of thin disks.Comment: Chapter accepted to appear in Planets, Stars and Stellar Systems, vol 5, ed G. Gilmore. 32 pages, 17 figures. Includes minor corrections made in proofs. Uses emulateapj.st

GWTC-3: Compact Binary Coalescences Observed by LIGO and Virgo During the Second Part of the Third Observing Run

The third Gravitational-wave Transient Catalog (GWTC-3) describes signals detected with Advanced LIGO and Advanced Virgo up to the end of their third observing run. Updating the previous GWTC-2.1, we present candidate gravitational waves from compact binary coalescences during the second half of the third observing run (O3b) between 1 November 2019, 15:00 UTC and 27 March 2020, 17:00 UTC. There are 35 compact binary coalescence candidates identified by at least one of our search algorithms with a probability of astrophysical origin $p_\mathrm{astro} > 0.5$. Of these, 18 were previously reported as low-latency public alerts, and 17 are reported here for the first time. Based upon estimates for the component masses, our O3b candidates with $p_\mathrm{astro} > 0.5$ are consistent with gravitational-wave signals from binary black holes or neutron star-black hole binaries, and we identify none from binary neutron stars. However, from the gravitational-wave data alone, we are not able to measure matter effects that distinguish whether the binary components are neutron stars or black holes. The range of inferred component masses is similar to that found with previous catalogs, but the O3b candidates include the first confident observations of neutron star-black hole binaries. Including the 35 candidates from O3b in addition to those from GWTC-2.1, GWTC-3 contains 90 candidates found by our analysis with $p_\mathrm{astro} > 0.5$ across the first three observing runs. These observations of compact binary coalescences present an unprecedented view of the properties of black holes and neutron stars

Search for Eccentric Black Hole Coalescences during the Third Observing Run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass $M>70$ $M_\odot$) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities $0 < e \leq 0.3$ at $0.33$ Gpc$^{-3}$ yr$^{-1}$ at 90\% confidence level.Comment: 24 pages, 5 figure

Open data from the third observing run of LIGO, Virgo, KAGRA and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in April of 2019 and lasting six months, O3b starting in November of 2019 and lasting five months, and O3GK starting in April of 2020 and lasting 2 weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main dataset, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages.Comment: 27 pages, 3 figure

GWTC-2.1: Deep Extended Catalog of Compact Binary Coalescences Observed by LIGO and Virgo During the First Half of the Third Observing Run

The second gravitational-wave transient catalog, GWTC-2, reported on 39 compact binary coalescences observed by the Advanced LIGO and Advanced Virgo detectors between 1 April 2019 15:00 UTC and 1 October 2019 15:00 UTC. Here, we present GWTC-2.1, which reports on a deeper list of candidate events observed over the same period. We analyze the final version of the strain data over this period, which is now publicly released. We employ three matched-filter search pipelines for candidate identification, and estimate the probability of astrophysical origin for each candidate event. While GWTC-2 used a false alarm rate threshold of 2 per year, we include in GWTC-2.1, 1201 candidates that pass a false alarm rate threshold of 2 per day. We calculate the source properties of a subset of 44 high-significance candidates that have a probability of astrophysical origin greater than 0.5, using the default priors. Of these candidates, 36 have been reported in GWTC-2. If the 8 additional high-significance candidates presented here are astrophysical, the mass range of candidate events that are unambiguously identified as binary black holes (both objects $\geq 3M_\odot$) is increased compared to GWTC-2, with total masses from $\sim 14M_\odot$ for GW190924_021846 to $\sim 184M_\odot$ for GW190426_190642. The primary components of two new candidate events (GW190403_051519 and GW190426_190642) fall in the mass gap predicted by pair-instability supernova theory. We also expand the population of binaries with significantly asymmetric mass ratios reported in GWTC-2 by an additional two events ($q \lt 0.61$ and $q \lt 0.62$ at $90\%$ credibility for GW190403_051519 and GW190917_114630 respectively), and find that 2 of the 8 new events have effective inspiral spins $\chi_\mathrm{eff} > 0$ (at $90\%$ credibility), while no binary is consistent with $\chi_\mathrm{eff} \lt 0$ at the same significance