DeepGlow: an efficient neural-network emulator of physical afterglow models for gamma-ray bursts and gravitational-wave events

Gamma-ray bursts (GRBs) and double neutron-star merger gravitational wave events are followed by afterglows that shine from X-rays to radio, and these broadband transients are generally interpreted using analytical models. Such models are relatively fast to execute, and thus easily allow estimates of the energy and geometry parameters of the blast wave, through many trial-and-error model calculations. One problem, however, is that such analytical models do not capture the underlying physical processes as well as more realistic relativistic numerical hydrodynamic (RHD) simulations do. Ideally, those simulations are used for parameter estimation instead, but their computational cost makes this intractable. To this end, we present DeepGlow, a highly efficient neural network architecture trained to emulate a computationally costly RHD-based model of GRB afterglows, to within a few percent accuracy. As a first scientific application, we compare both the emulator and a different analytical model calibrated to RHD simulations, to estimate the parameters of a broadband GRB afterglow. We find consistent results between these two models, and also give further evidence for a stellar wind progenitor environment around this GRB source. DeepGlow fuses simulations that are otherwise too complex to execute over all parameters, to real broadband data of current and future GRB afterglows.Comment: 10 pages, 6 figures, 5 tables, accepted version. Code availabl

Investigating the detection rates and inference of gravitational-wave and radio emission from black hole neutron star mergers

Black hole neutron star (BHNS) mergers have recently been detected through their gravitational-wave (GW) emission. BHNS mergers could also produce electromagnetic (EM) emission as a short gamma-ray burst (sGRB), and/or an sGRB afterglow upon interaction with the circummerger medium. Here, we make predictions for the expected detection rates with the Square Kilometre Array Phase 1 (SKA1) of sGRB radio afterglows associated with BHNS mergers. We also investigate the benefits of a multimessenger analysis in inferring the properties of the merging binary. We simulate a population of BHNS mergers and estimate their sGRB afterglow flux to obtain the detection rates with SKA1. We investigate how this rate depends on the GW detector sensitivity, the primary black hole (BH) spin, and the neutron star equation of state. We then perform a multimessenger Bayesian inference study on a fiducial BHNS merger. We simulate its sGRB afterglow and GW emission and take systematic errors into account. The expected rates of a combined GW and radio detection with the current generation GW detectors are likely low. Due to the much increased sensitivity of future GW detectors like the Einstein Telescope, the chances of an sGRB localisation and radio detection increase substantially. The unknown distribution of the BH spin has a big influence on the detection rates, however, and it is a large source of uncertainty. Furthermore, for our fiducial BHNS merger we are able to infer both the binary source parameters as well as the parameters of the sGRB afterglow simultaneously when combining the GW and radio data. The radio data provides useful extra information on the binary parameters such as the mass ratio but this is limited by the systematic errors involved. A better understanding of the systematics will further increase the amount of information on the binary parameters that can be extracted from this radio data.Comment: 17 pages, 12 figures, accepted version (Astronomy and Astrophysics

Forecasts for detecting the gravitational-wave memory effect with Advanced LIGO and Virgo

The detection of gravitational waves (GWs) from binary black holes (BBHs) has allowed the theory of general relativity to be tested in a previously unstudied regime: that of strong curvature and high GW luminosities. One distinctive and measurable effect associated with this aspect of the theory is the nonlinear GW memory effect. The GW memory effect is characterized by its effect on freely falling observers: the proper distance between their locations differs before and after a burst of GWs passes by their locations. Gravitational-wave interferometers, like the LIGO and Virgo detectors, can measure features of this effect from a single BBH merger, but previous work has shown that it will require an event that is significantly more massive and closer than any previously detected GW event. Finding evidence for the GW memory effect within the entire population of BBH mergers detected by LIGO and Virgo is more likely to occur sooner. A prior study has shown that the GW memory effect could be detected in a population of BBHs consisting of binaries like the first GW150914 event after roughly one-hundred events. In this paper, we compute forecasts of the time it will take the advanced LIGO and Virgo detectors (when the detectors are operating at their design sensitivities) to find evidence for the GW memory effect in a population of BBHs that is consistent with the measured population of events in the first two observing runs of the LIGO detectors. We find that after five years of data collected by the advanced LIGO and Virgo detectors the signal-to-noise ratio for the nonlinear GW memory effect in the population will be about three (near a previously used threshold for detection). We point out that the different approximation methods used to compute the GW memory effect can lead to notably different signal-to-noise ratios.Comment: 20 pages, 6 figure

ChIP-less analysis of chromatin states

BACKGROUND: Histone post-translational modifications (PTMs) are key epigenetic regulators in chromatin-based processes. Increasing evidence suggests that vast combinations of PTMs exist within chromatin histones. These complex patterns, rather than individual PTMs, are thought to define functional chromatin states. However, the ability to interrogate combinatorial histone PTM patterns at the nucleosome level has been limited by the lack of direct molecular tools. RESULTS: Here we demonstrate an efficient, quantitative, antibody-free, chromatin immunoprecipitation-less (ChIP-less) method for interrogating diverse epigenetic states. At the heart of the workflow are recombinant chromatin reader domains, which target distinct chromatin states with combinatorial PTM patterns. Utilizing a newly designed combinatorial histone peptide microarray, we showed that three reader domains (ATRX-ADD, ING2-PHD and AIRE-PHD) displayed greater specificity towards combinatorial PTM patterns than corresponding commercial histone antibodies. Such specific recognitions were employed to develop a chromatin reader-based affinity enrichment platform (matrix-assisted reader chromatin capture, or MARCC). We successfully applied the reader-based platform to capture unique chromatin states, which were quantitatively profiled by mass spectrometry to reveal interconnections between nucleosomal histone PTMs. Specifically, a highly enriched signature that harbored H3K4me0, H3K9me2/3, H3K79me0 and H4K20me2/3 within the same nucleosome was identified from chromatin enriched by ATRX-ADD. This newly reported PTM combination was enriched in heterochromatin, as revealed by the associated DNA. CONCLUSIONS: Our results suggest the broad utility of recombinant reader domains as an enrichment tool specific to combinatorial PTM patterns, which are difficult to probe directly by antibody-based approaches. The reader affinity platform is compatible with several downstream analyses to investigate the physical coexistence of nucleosomal PTM states associated with specific genomic loci. Collectively, the reader-based workflow will greatly facilitate our understanding of how distinct chromatin states and reader domains function in gene regulatory mechanisms

Aligning a New Reference Genetic Map of Lupinus angustifolius with the Genome Sequence of the Model Legume, Lotus japonicus

We have developed a dense reference genetic map of Lupinus angustifolius (2n = 40) based on a set of 106 publicly available recombinant inbred lines derived from a cross between domesticated and wild parental lines. The map comprised 1090 loci in 20 linkage groups and three small clusters, drawing together data from several previous mapping publications plus almost 200 new markers, of which 63 were gene-based markers. A total of 171 mainly gene-based, sequence-tagged site loci served as bridging points for comparing the Lu. angustifolius genome with the genome sequence of the model legume, Lotus japonicus via BLASTn homology searching. Comparative analysis indicated that the genomes of Lu. angustifolius and Lo. japonicus are highly diverged structurally but with significant regions of conserved synteny including the region of the Lu. angustifolius genome containing the pod-shatter resistance gene, lentus. We discuss the potential of synteny analysis for identifying candidate genes for domestication traits in Lu. angustifolius and in improving our understanding of Fabaceae genome evolution

Incremental prognostic value of multi-slice computed tomography coronary angiography over coronary artery calcium scoring in patients with suspected coronary artery disease

Aims The purpose of this study was to assess the relationship between calcium scoring (CS) and multi-slice computed tomography coronary angiography (MSCTA) and to determine if MSCTA has an incremental prognostic value to CS. Methods and results In 432 patients (59% male, age 58 ± 11 years) referred for cardiac evaluation owing to suspected coronary artery disease (CAD), CS and 64-slice MSCTA were performed. The following events were combined in a composite endpoint: all-cause mortality, non-fatal infarction, and unstable angina requiring revascularization. CS was 0 in 147 (34%) patients, CS 1-99 was present in 122 (28%), CS 100-399 in 75 (17%), CS 400-999 in 56 (13%), and CS ≥ 1000 in 32 (7%). MSCTA was normal in 133 (31%) patients, MSCTA 30-50% stenosis was observed in 190 (44%), and MSCTA ≥50% stenosis in 109 (25%). During follow-up [median 670 days (25th-75th percentile: 418-895)], an event occurred in 21 patients (4.9%). After multivariate correction for CS, MSCTA ≥ 50% stenosis, the number of diseased segments, obstructive segments, and non-calcified plaques were independent predictors with an incremental prognostic value to CS. Conclusion MSCTA provides additional information to CS regarding stenosis severity and plaque composition. This additional information was shown to translate into incremental prognostic value over C

Better Palliative Care for people with a Dementia: Summary of InterdisciplinaryWorkshop Highlighting Current Gaps and Recommendations for Future Research

Background: Dementia is the most common neurological disorder worldwide and is a life-limiting condition, but very often is not recognised as such. People with dementia, and their carers, have been shown to have palliative care needs equal in extent to those of cancer patients. However, many people with advanced dementia are not routinely being assessed to determine their palliative care needs, and it is not clear why this is so. Main body: An interdisciplinary workshop on "Palliative Care in Neurodegeneration, with a focus on Dementia", was held in Cork, Ireland, in May 2016. The key aim of this workshop was to discuss the evidence base for palliative care for people with dementia, to identify 'gaps' for clinical research, and to make recommendations for interdisciplinary research practice. To lead the discussion throughout the day a multidisciplinary panel of expert speakers were brought together, including both researchers and clinicians from across Ireland and the UK. Targeted invitations were sent to attendees ensuring all key stakeholders were present to contribute to discussions. In total, 49 experts representing 17 different academic and practice settings, attended. Key topics for discussion were pre-selected based on previously identified research priorities (e.g. James Lind Alliance) and stakeholder input. Key discussion topics included: i. Advance Care Planning for people with Dementia; ii. Personhood in End-of-life Dementia care; iii. Topics in the care of advanced dementia at home. These topics were used as a starting point, and the ethos of the workshop was that the attendees could stimulate discussion and debate in any relevant area, not just the key topics, summarised under iv. Other priorities. Conclusions: The care experienced by people with dementia and their families has the potential to be improved; palliative care frameworks may have much to offer in this endeavour. However, a solid evidence base is required to translate palliative care into practice in the context of dementia. This paper presents suggested research priorities as a starting point to build this evidence base. An interdisciplinary approach to research and priority setting is essential to develop actionable knowledge in this area

Chromatic periodic activity down to 120 MHz in a Fast Radio Burst

Fast radio bursts (FRBs) are extragalactic astrophysical transients whose brightness requires emitters that are highly energetic, yet compact enough to produce the short, millisecond-duration bursts. FRBs have thus far been detected between 300 MHz and 8 GHz, but lower-frequency emission has remained elusive. A subset of FRBs is known to repeat, and one of those sources, FRB 20180916B, does so with a 16.3 day activity period. Using simultaneous Apertif and LOFAR data, we show that FRB 20180916B emits down to 120 MHz, and that its activity window is both narrower and earlier at higher frequencies. Binary wind interaction models predict a narrower periodic activity window at lower frequencies, which is the opposite of our observations. Our detections establish that low-frequency FRB emission can escape the local medium. For bursts of the same fluence, FRB 20180916B is more active below 200 MHz than at 1.4 GHz. Combining our results with previous upper-limits on the all-sky FRB rate at 150 MHz, we find that there are 3-450 FRBs/sky/day above 50 Jy ms at 90% confidence. We are able to rule out the scenario in which companion winds cause FRB periodicity. We also demonstrate that some FRBs live in clean environments that do not absorb or scatter low-frequency radiation.Comment: 50 pages, 14 figures, 3 tables, submitte

Effects of Neuraxial Blockade May Be Difficult To Study Using Large Randomized Controlled Trials: The PeriOperative Epidural Trial (POET) Pilot Study

Early randomized controlled trials have suggested that neuraxial blockade may reduce cardiorespiratory complications after non-cardiothoracic surgery, but recent larger trials have been inconclusive. We conducted a pilot study to assess the feasibility of conducting a large multicentre randomized controlled trial in Canada.After Research Ethics Board approvals from the participating institutions, subjects were recruited if they were > or = 45 years old, had an expected hospital stay > or = 48 hours, were undergoing a noncardiothoracic procedure amenable to epidural analgesia, met one of six risk criteria, and did not have contraindications to neuraxial blockade. After informed consent, subjects were randomly allocated to combined epidural analgesia (epidural group) and neuraxial anesthesia, with or without general anesthesia, or intravenous opioid analgesia (IV group) and general anesthesia. The primary outcomes were the rate of recruitment and the percents of eligible patients recruited, crossed over, and followed completely. Feasibility targets were defined a priori. A blinded, independent committee adjudicated the secondary clinical outcomes. Subjects were followed daily while in hospital and then at 30 days after surgery. Analysis was intention-to-treat. Over a 15-month period, the recruitment rate was 0.5+/-0.3 (mean+/-SEM) subjects per week per centre; 112/494 (22.7%) eligible subjects were recruited at four tertiary-care teaching hospitals in Canada. Thirteen (26.5%) of 49 subjects in the epidural group crossed over to the IV group; seven (14.3%) were due to failed or inadequate analgesia or complications from epidural analgesia. Five (9.8%) of 51 subjects in the IV group crossed over to the epidural group but none were due to inadequate analgesia or complications. Ninety-eight (97.0%) of 101 subjects were successfully followed up until 30 days after their surgery.Of the criteria we defined for the feasibility of a full-scale trial, only the follow-up target was met. The other feasibility outcomes did not meet our preset criteria for success. The results suggest that a large multicentre trial may not be a feasible design to study the perioperative effects of neuraxial blockade.ClinicalTrials.gov NCT 0221260 Controlled-Trials.com ISRCTN 35629817

Assessing a risk tailored intervention to prevent disabling low back pain - protocol of a cluster randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Although most patients with low back pain (LBP) recover within a few weeks a significant proportion has recurrent episodes or will develop chronic low back pain. Several mainly psychosocial risk factors for developing chronic LBP have been identified. However, effects of preventive interventions aiming at behavioural risk factors and unfavourable cognitions have yielded inconsistent results. Risk tailored interventions may provide a cost efficient and effective means to take systematic account of the individual risk factors but evidence is lacking.</p> <p>Methods/Design</p> <p>This study will be a cluster-randomised controlled trial comparing screening and a subsequent risk tailored intervention for patients with low back pain to prevent chronic low back pain compared to treatment as usual in primary care. A total of 600 patients from 20 practices in each study arm will be recruited in Berlin and Goettingen. The intervention comprises the following elements: Patients will be assigned to one of four risk groups based on a screening questionnaire. Subsequently they receive an educational intervention including information and counselling tailored to the risk group. A telephone/email consulting service for back pain related problems are offered independent of risk group assignment. The primary outcomes will be functional capacity and sick leave.</p> <p>Discussion</p> <p>This trial will evaluate the effectiveness of screening for risk factors for chronic low back pain followed by a risk tailored intervention to prevent chronic low back pain. This trial will contribute new evidence regarding the flexible use of individual physical and psychosocial risk factors in general practice.</p> <p>Trial registration</p> <p>ISRCTN 68205910</p