K2P2^2 −- A photometry pipeline for the K2 mission

With the loss of a second reaction wheel, resulting in the inability to point continuously and stably at the same field of view, the NASA Kepler satellite recently entered a new mode of observation known as the K2 mission. The data from this redesigned mission present a specific challenge; the targets systematically drift in position on a ~6 hour time scale, inducing a significant instrumental signal in the photometric time series --- this greatly impacts the ability to detect planetary signals and perform asteroseismic analysis. Here we detail our version of a reduction pipeline for K2 target pixel data, which automatically: defines masks for all targets in a given frame; extracts the target's flux- and position time series; corrects the time series based on the apparent movement on the CCD (either in 1D or 2D) combined with the correction of instrumental and/or planetary signals via the KASOC filter (Handberg & Lund 2014), thus rendering the time series ready for asteroseismic analysis; computes power spectra for all targets, and identifies potential contaminations between targets. From a test of our pipeline on a sample of targets from the K2 campaign 0, the recovery of data for multiple targets increases the amount of potential light curves by a factor ${\geq}10$. Our pipeline could be applied to the upcoming TESS (Ricker et al. 2014) and PLATO 2.0 (Rauer et al. 2013) missions.Comment: 14 pages, 20 figures, Accepted for publication in The Astrophysical Journal (Apj

The Safety and Efficacy of Phage Therapy for Infections in Cardiac and Peripheral Vascular Surgery:A Systematic Review

New approaches to managing infections in cardiac and peripheral vascular surgery are required to reduce costs to patients and healthcare providers. Bacteriophage (phage) therapy is a promising antimicrobial approach that has been recommended for consideration in antibiotic refractory cases. We systematically reviewed the clinical evidence for phage therapy in vascular surgery to support the unlicensed use of phage therapy and inform future research. Three electronic databases were searched for articles that reported primary data about human phage therapy for infections in cardiac or peripheral vascular surgery. Fourteen reports were eligible for inclusion, representing 40 patients, among which an estimated 70.3% of patients (n = 26/37) achieved clinical resolution. A further 10.8% (n = 4/37) of patients showed improvement and 18.9% (n = 7/37) showed no improvement. Six of the twelve reports that commented on the safety of phage therapy did not report adverse effects. No adverse effects documented in the remaining six reports were directly linked to phages but reflected the presence of manufacturing contaminants or release of bacterial debris following bacterial lysis. The reports identified by this review suggest that appropriately purified phages represent a safe and efficacious treatment option for infections in cardiac and peripheral vascular surgery.</p

The Safety and Efficacy of Phage Therapy for Infections in Cardiac and Peripheral Vascular Surgery:A Systematic Review

New approaches to managing infections in cardiac and peripheral vascular surgery are required to reduce costs to patients and healthcare providers. Bacteriophage (phage) therapy is a promising antimicrobial approach that has been recommended for consideration in antibiotic refractory cases. We systematically reviewed the clinical evidence for phage therapy in vascular surgery to support the unlicensed use of phage therapy and inform future research. Three electronic databases were searched for articles that reported primary data about human phage therapy for infections in cardiac or peripheral vascular surgery. Fourteen reports were eligible for inclusion, representing 40 patients, among which an estimated 70.3% of patients (n = 26/37) achieved clinical resolution. A further 10.8% (n = 4/37) of patients showed improvement and 18.9% (n = 7/37) showed no improvement. Six of the twelve reports that commented on the safety of phage therapy did not report adverse effects. No adverse effects documented in the remaining six reports were directly linked to phages but reflected the presence of manufacturing contaminants or release of bacterial debris following bacterial lysis. The reports identified by this review suggest that appropriately purified phages represent a safe and efficacious treatment option for infections in cardiac and peripheral vascular surgery.</p

Sensorimotor Function in Progressive Multiple Sclerosis

Background: A sensitive test reflecting subtle sensorimotor changes throughout disease progression independent of mobility impairment is currently lacking in progressive multiple sclerosis. Objectives: We examined non-ambulatory measures of upper and lower extremity sensorimotor function that may reveal differences between relapsing–remitting and progressive forms of multiple sclerosis. Methods: Cutaneous sensitivity, proprioception, central motor function and mobility were assessed in 32 relapsing–remitting and 31 progressive multiple sclerosis patients and 30 non-multiple sclerosis controls. Results: Cutaneous sensation differed between relapsing–remitting and progressive multiple sclerosis at the foot and to a lesser extent the hand. Proprioception function in the upper but not the lower extremity differed between relapsing–remitting and progressive multiple sclerosis, but was different for both upper and lower extremities between multiple sclerosis patients and non-multiple sclerosis controls. Foot-tap but not hand-tap speed was slower in progressive compared to relapsing–remitting multiple sclerosis, suggestive of greater central motor function impairment in the lower extremity in progressive multiple sclerosis. In addition, the non-ambulatory sensorimotor measures were more sensitive in detecting differences between relapsing–remitting and progressive multiple sclerosis than mobility assessed with the 25-foot walk test. Conclusion: This study provides novel information about changes in sensorimotor function in progressive compared with relapsing–remitting forms of multiple sclerosis, and in particular the importance of assessing both upper and lower extremity function. Importantly, our findings showed loss of proprioceptive function in multiple sclerosis but also in progressive compared to relapsing–remitting multiple sclerosis

A qualitative feasibility study to inform a randomised controlled trial of fluid bolus therapy in septic shock

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. Objective The Fluids in Shock (FiSh) Trial proposes to evaluate whether restrictive fluid bolus therapy (10 mL/ kg) is more beneficial than current recommended practice (20 mL/kg) in the resuscitation of children with septic shock in the UK. This qualitative feasibility study aimed to explore acceptability of the FiSh Trial, including research without prior consent (RWPC), potential barriers to recruitment and participant information for a pilot trial. Design Qualitative interview study involving parents of children who had presented to a UK emergency department or been admitted to a paediatric intensive care unit with severe infection in the previous 3 years. Participants Twenty-one parents (seven bereaved) were interviewed 16 (median) months since their child’s hospital admission (range: 1–41). results All parents said they would have provided consent for the use of their child’s data in the FiSh Trial. The majority were unfamiliar with RWPC, yet supported its use. Parents were initially concerned about the change from currently recommended treatment, yet were reassured by explanations of the current evidence base, fluid bolus therapy and monitoring procedures. Parents made recommendations about the timing of the research discussion and content of participant information. Bereaved parents stated that recruiters should not discuss research immediately after a child’s death, but supported a personalised postal’opt-out’ approach to consent. conclusions Findings show that parents whose child has experienced severe infection supported the proposed FiSh Trial, including the use of RWPC. Parents’ views informed the development of the pilot trial protocol and site staff training. trial registration number ISRCTN15244462—results

Effectiveness and Safety of Adalimumab Biosimilar SB5 in IBD:Outcomes in Originator to SB5 Switch, Double Biosimilar Switch and Bio-Naieve SB5 Observational Cohorts

BACKGROUND AND AIMS: Multiple adalimumab [ADA] biosimilars are now approved for use in inflammatory bowel disease [IBD]; however, effectiveness and safety data remain scarce. We aimed to investigate long-term outcomes of the ADA biosimilar SB5 in IBD patients following a switch from the ADA originator [SB5-switch cohort] or after start of SB5 [SB5-start cohort]. METHODS: We performed an observational cohort study in a tertiary IBD referral centre. All IBD patients treated with Humira underwent an elective switch to SB5. We identified all these patients in a biological prescription database that prospectively registered all ADA start and stop dates including brand names. Data on IBD phenotype, C-reactive protein [CRP], drug persistence, ADA drug and antibody levels, and faecal calprotectin were collected. RESULTS: In total, 481 patients were treated with SB5, 256 in the SB5-switch cohort (median follow-up: 13.7 months [IQR 8.6–15.2]) and 225 in the SB5-start cohort [median follow-up: 8.3 months [4.2–12.8]). Of the SB5-switch cohort, 70.8% remained on SB5 beyond 1 year; 90/256 discontinued SB5, mainly due to adverse events [46/90] or secondary loss of response [37/90]. In the SB5-start cohort, 81/225 discontinued SB5, resulting in SB5-drug persistence of 60.3% beyond 1 year. No differences in clinical remission [p = 0.53], CRP [p = 0.80], faecal calprotectin [p = 0.40] and ADA trough levels [p = 0.55] were found between baseline, week 26 and week 52 following switch. Injection site pain was the most frequently reported adverse event. CONCLUSION: Switching from ADA originator to SB5 appeared effective and safe in this study with over 12 months of follow-up

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

A consensus protocol for the recovery of mercury methylation genes from metagenomes

Mercury (Hg) methylation genes (hgcAB) mediate the formation of the toxic methylmercury and have been identified from diverse environments, including freshwater and marine ecosystems, Arctic permafrost, forest and paddy soils, coal-ash amended sediments, chlor-alkali plants discharges and geothermal springs. Here we present the first attempt at a standardized protocol for the detection, identification and quantification of hgc genes from metagenomes. Our Hg-cycling microorganisms in aquatic and terrestrial ecosystems (Hg-MATE) database, a catalogue of hgc genes, provides the most accurate information to date on the taxonomic identity and functional/metabolic attributes of microorganisms responsible for Hg methylation in the environment. Furthermore, we introduce "marky-coco", a ready-to-use bioinformatic pipeline based on de novo single-metagenome assembly, for easy and accurate characterization of hgc genes from environmental samples. We compared the recovery of hgc genes from environmental metagenomes using the marky-coco pipeline with an approach based on coassembly of multiple metagenomes. Our data show similar efficiency in both approaches for most environments except those with high diversity (i.e., paddy soils) for which a coassembly approach was preferred. Finally, we discuss the definition of true hgc genes and methods to normalize hgc gene counts from metagenomes

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio