Progress on core outcomes sets for critical care research

Purpose of review: Appropriate selection and definition of outcome measures are essential for clinical trials to be maximally informative. Core outcome sets (an agreed, standardized collection of outcomes measured and reported in all trials for a specific clinical area) were developed due to established inconsistencies in trial outcome selection. This review discusses the rationale for, and methods of, core outcome set development, as well as current initiatives in critical care.

Recent findings: Recent systematic reviews of reported outcomes and measurement instruments relevant to the critically ill highlight inconsistencies in outcome selection, definition, and measurement, thus establishing the need for core outcome sets. Current critical care initiatives include development of core outcome sets for trials aimed at reducing mechanical ventilation duration; rehabilitation following critical illness; long-term outcomes in acute respiratory failure; and epidemic and pandemic studies of severe acute respiratory infection.

Summary: Development and utilization of core outcome sets for studies relevant to the critically ill is in its infancy compared to other specialties. Notwithstanding, core outcome set development frameworks and guidelines are available, several sets are in various stages of development, and there is strong support from international investigator-led collaborations including the International Forum for Acute Care Trialists.

Constraints on explosive silicon burning in core-collapse supernovae from measured Ni/Fe ratios

Measurements of explosive nucleosynthesis yields in core-collapse supernovae provide tests for explosion models. We investigate constraints on explosive conditions derivable from measured amounts of nickel and iron after radioactive decays using nucleosynthesis networks with parameterized thermodynamic trajectories. The Ni/Fe ratio is for most regimes dominated by the production ratio of Ni-58/(Fe-54 + Ni-56), which tends to grow with higher neutron excess and with higher entropy. For SN 2012ec, a supernova (SN) that produced a Ni/Fe ratio of 3.4 +/- 1.2 times solar, we find that burning of a fuel with neutron excess eta approximate to 6 x 10(-3) is required. Unless the progenitor metallicity is over five times solar, the only layer in the progenitor with such a neutron excess is the silicon shell. SNe producing large amounts of stable nickel thus suggest that this deep-lying layer can be, at least partially, ejected in the explosion. We find that common spherically symmetric models of M-ZAMS less than or similar to 13 M-circle dot stars exploding with a delay time of less than one second (M-cut < 1.5 M-circle dot) are able to achieve such silicon-shell ejection. SNe that produce solar or subsolar Ni/Fe ratios, such as SN 1987A, must instead have burnt and ejected only oxygen-shell material, which allows a lower limit to the mass cut to be set. Finally, we find that the extreme Ni/Fe value of 60-75 times solar derived for the Crab cannot be reproduced by any realistic entropy burning outside the iron core, and neutrino-neutronization obtained in electron capture models remains the only viable explanation.

SN2012ca: a stripped envelope core-collapse SN interacting with dense circumstellar medium

We report optical and near-infrared observations of SN2012ca with the Public ESO Spectroscopy Survey of Transient Objects (PESSTO), spread over one year since discovery. The supernova (SN) bears many similarities to SN1997cy and to other events classified as Type IIn but which have been suggested to have a thermonuclear origin with narrow hydrogen lines produced when the ejecta impact a hydrogen-rich circumstellar medium (CSM). Our analysis, especially in the nebular phase, reveals the presence of oxygen, magnesium and carbon features. This suggests a core-collapse explanation for SN2012ca, in contrast to the thermonuclear interpretation proposed for some members of this group. We suggest that the data can be explained with a hydrogen- and helium-deficient SN ejecta (Type I) interacting with a hydrogen-rich CSM, but that the explosion was more likely a Type Ic core-collapse explosion than a Type Ia thermonuclear one. This suggests that two channels (both thermonuclear and stripped envelope core-collapse) may be responsible for these SN 1997cy-like events.

An ultraviolet-optical flare from the tidal disruption of a helium-rich stellar core

The flare of radiation from the tidal disruption and accretion of a star can be used as a marker for supermassive black holes that otherwise lie dormant and undetected in the centres of distant galaxies. Previous candidate flares have had declining light curves in good agreement with expectations, but with poor constraints on the time of disruption and the type of star disrupted, because the rising emission was not observed. Recently, two `relativistic' candidate tidal disruption events were discovered, each of whose extreme X-ray luminosity and synchrotron radio emission were interpreted as the onset of emission from a relativistic jet. Here we report a luminous ultraviolet-optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696. The observed continuum is cooler than expected for a simple accreting debris disk, but the well-sampled rise and decay of the light curve follow the predicted mass accretion rate and can be modelled to determine the time of disruption to an accuracy of two days. The black hole has a mass of about two million solar masses, modulo a factor dependent on the mass and radius of the star disrupted. On the basis of the spectroscopic signature of ionized helium from the unbound debris, we determine that the disrupted star was a helium-rich stellar core.

Experimental study on PC hollow-core slab strengthened with bamboo plates

An experimental study on strengthening prestressed concrete (PC) hollow-core slabs was conducted. Nine PC hollow-core slabs were tested, including three unstrengthened reference slabs and six slabs strengthened with bamboo plates. The results show that compared with unreinforced slabs, the cracking loads of PC hollow-core slabs strengthened with bamboo plates increase by 5% to 96% (with an average of 41%), the loads at allowable deflection increase by 8% to 76% (with an average of 35%), and the ultimate loads increase by 83% to 184% (with an average of 123%), respectively. All the degrees of improvement in the crack load, allowable load and ultimate load increase with the increase in the thickness and width of the bamboo plates. With the increase in the loads, the strain distribution along the height of the strengthened slabs at the mid-span basically remains a plan-assumption. With the increase in the thickness and width of the bamboo plates, both the bamboo tensile strain on the tensile face and the concrete compressive strain on the compression face of the strengthened slabs decrease under the same load level.

COS-STAR: a reporting guideline for studies developing core outcome sets (protocol)

BACKGROUND: Core outcome sets can increase the efficiency and value of research and, as a result, there are an increasing number of studies looking to develop core outcome sets (COS). However, the credibility of a COS depends on both the use of sound methodology in its development and clear and transparent reporting of the processes adopted. To date there is no reporting guideline for reporting COS studies. The aim of this programme of research is to develop a reporting guideline for studies developing COS and to highlight some of the important methodological considerations in the process.

METHODS/DESIGN: The study will include a reporting guideline item generation stage which will then be used in a Delphi study. The Delphi study is anticipated to include two rounds. The first round will ask stakeholders to score the items listed and to add any new items they think are relevant. In the second round of the process, participants will be shown the distribution of scores for all stakeholder groups separately and asked to re-score. A final consensus meeting will be held with an expert panel and stakeholder representatives to review the guideline item list. Following the consensus meeting, a reporting guideline will be drafted and review and testing will be undertaken until the guideline is finalised. The final outcome will be the COS-STAR (Core Outcome Set-STAndards for Reporting) guideline for studies developing COS and a supporting explanatory document.

DISCUSSION: To assess the credibility and usefulness of a COS, readers of a COS development report need complete, clear and transparent information on its methodology and proposed core set of outcomes. The COS-STAR guideline will potentially benefit all stakeholders in COS development: COS developers, COS users, e.g. trialists and systematic reviewers, journal editors, policy-makers and patient groups.

Core outcome sets and trial registries

Some reasons for registering trials might be considered as self-serving, such as satisfying the requirements of a journal in which the researchers wish to publish their eventual findings or publicising the trial to boost recruitment. Registry entries also help others, including systematic reviewers, to know about ongoing or unpublished studies and contribute to reducing research waste by making it clear what studies are ongoing. Other sources of research waste include inconsistency in outcome measurement across trials in the same area, missing data on important outcomes from some trials, and selective reporting of outcomes. One way to reduce this waste is through the use of core outcome sets: standardised sets of outcomes for research in specific areas of health and social care. These do not restrict the outcomes that will be measured, but provide the minimum to include if a trial is to be of the most use to potential users. We propose that trial registries, such as ISRCTN, encourage researchers to note their use of a core outcome set in their entry. This will help people searching for trials and those worried about selective reporting in closed trials. Trial registries can facilitate these efforts to make new trials as useful as possible and reduce waste. The outcomes section in the entry could prompt the researcher to consider using a core outcome set and facilitate the specification of that core outcome set and its component outcomes through linking to the original core outcome set. In doing this, registries will contribute to the global effort to ensure that trials answer important uncertainties, can be brought together in systematic reviews, and better serve their ultimate aim of improving health and well-being through improving health and social care.

Towards core outcome set (COS) development: a follow-up descriptive survey of outcomes in Cochrane reviews

BACKGROUND: A core outcome set (COS) can address problems of outcome heterogeneity and outcome reporting bias in trials and systematic reviews, including Cochrane reviews, helping to reduce waste. One of the aims of the international Core Outcome Measures in Effectiveness Trials (COMET) Initiative is to link the development and use of COS with the outcomes specified and reported in Cochrane reviews, including the outcomes listed in the summary of findings (SoF) tables. As part of this work, an earlier exploratory survey of the outcomes of newly published 2007 and 2011 Cochrane reviews was performed. This survey examined the use of COS, the variety of specified outcomes, and outcome reporting in Cochrane reviews by Cochrane Review Group (CRG). To examine changes over time and to explore outcomes that were repeatedly specified over time in Cochrane reviews by CRG, we conducted a follow-up survey of outcomes in 2013 Cochrane reviews.

METHODS: A descriptive survey of outcomes in Cochrane reviews that were first published in 2013. Outcomes specified in the methods sections and reported in the results section of the Cochrane reviews were examined by CRG. We also explored the uptake of SoF tables, the number of outcomes included in these, and the quality of the evidence for the outcomes.

RESULTS: Across the 50 CRGs, 375 Cochrane reviews that included at least one study specified a total of 3142 outcomes. Of these outcomes, 32 % (1008) were not reported in the results section of these reviews. For 23 % (233) of these non-reported outcomes, we did not find any reason in the text of the review for this non-report. Fifty-seven percent (216/375) of reviews included a SoF table.

CONCLUSIONS: The proportion of specified outcomes that were reported in Cochrane reviews had increased in 2013 (68 %) compared to 2007 (61 %) and 2011 (65 %). Importantly, 2013 Cochrane reviews that did not report specified outcomes were twice as likely to provide an explanation for why the outcome was not reported. There has been an increased uptake of SoF tables in Cochrane reviews. Outcomes that were repeatedly specified in Cochrane reviews by CRG in 2007, 2011, and 2013 may assist COS development.

FPGA Soft-core Processors, Compiler and Hardware Optimizations validated using HOG

There is demand for an easily programmable, high performance image processing platform based on FPGAs. In previous work, a novel, high performance processor - IPPro was developed and a Histogram of Orientated Gradients (HOG) algorithm study undertaken on a Xilinx Zynq platform. Here, we identify and explore a number of mapping strategies to improve processing efficiency for soft-cores and a number of options for creation of a division coprocessor. This is demonstrated for the revised high definition HOG implementation on a Zynq platform, resulting in a performance of 328 fps which represents a 146% speed improvement over the original realization and a tenfold reduction in energy.

Soft-core Stream Processor for Sliding Window Applications

Software-programmable `soft' processors have shown tremendous potential for efficient realisation of high performance signal processing operations on Field Programmable Gate Array (FPGA), whilst lowering the design burden by avoiding the need to design fine-grained custom circuit archi-tectures. However, the complex data access patterns, high memory bandwidth and computational requirements of sliding window applications, such as Motion Estimation (ME) and Matrix Multiplication (MM), lead to low performance, inefficient soft processor realisations. This paper resolves this issue, showing how by adding support for block data addressing and accelerators for high performance loop execution, performance and resource efficiency over four times better than current best-in-class metrics can be achieved. In addition, it demonstrates the first recorded real-time soft ME estimation realisation for H.263 systems.