Emergency Stroke Calls: Obtaining Rapid Telephone Triage (ESCORTT) - a programme of research to facilitate recognition of stroke by emergency medical dispatchers

Background: Rapid access to emergency stroke care can reduce death and disability by enabling immediate provision of interventions such as thrombolysis, physiological monitoring and stabilisation. One of the ways that access to services can be facilitated is through emergency medical service (EMS)dispatchers. The sensitivity of EMS dispatchers for identifying stroke is < 50%. Studies have shown that activation of the EMSs is the single most important factor in the rapid triage and treatment of acute stroke patients. Objectives: To facilitate recognition of stroke by emergency medical dispatchers (EMDs). Design: An eight-phase mixed-methods study. Phase 1: a retrospective cohort study exploring stroke diagnosis. Phase 2: semi-structured interviews exploring public and EMS interactions. Phases 3 and 4: a content analysis of 999 calls exploring the interaction between the public and EMDs. Phases 5–7: development and implementation of stroke-specific online training (based on phases 1–4). Phase 8: an interrupted time series exploring the impact of the online training. Setting: One ambulance service and four hospitals. Participants: Patients arriving at hospital by ambulance with stroke suspected somewhere on the stroke pathway (phases 1 and 8). Patients arriving at hospital by ambulance with a final diagnosis of stroke (phase 2). Calls to the EMSs relating to phase 1 patients (phases 3 and 4). EMDs (phase 7). Interventions: Stroke-specific online training package, designed to improve recognition of stroke for EMDs. Main outcome measures: Phase 1: symptoms indicative of a final and dispatch diagnosis of stroke. Phase 2: factors involved in the decision to call the EMSs when stroke is suspected. Phases 3 and 4: keywords used by the public when describing stroke and non-stroke symptoms to EMDs. Phase 8: proportion of patients with a final diagnosis of stroke correctly dispatched as stroke by EMDs. Results: Phase 1: for patients with a final diagnosis of stroke, facial weakness and speech problems were significantly associated with an EMD code of stroke. Phase 2: four factors were identified – perceived seriousness; seeking and receiving lay or professional advice; caller’s description of symptoms and emotional response to symptoms. Phases 3 and 4: mention of ‘stroke’ or one or more Face Arm Speech Test (FAST) items is much more common in stroke compared with non-stroke calls. Consciousness level was often difficult for callers to determine and/or communicate. Phase 8: there was a significant difference (p = 0.003) in proportions correctly dispatched as stroke – before the training was implemented 58 out of 92 (63%); during implementation of training 42 out of 48 (88%); and after training implemented 47 out of 59 (80%). Conclusions: EMDs should be aware that callers are likely to describe loss of function (e.g. unable to grip) rather than symptoms (e.g. weakness) and that callers using the word ‘stroke’ or describing facial weakness, limb weakness or speech problems are likely to be calling about a stroke. Ambiguities and contradictions in dialogue about consciousness level arise during ambulance calls for suspected and confirmed stroke. The online training package improved recognition of stroke by EMDs. Recommendations for future research include testing the effectiveness of the Emergency Stroke Calls: Obtaining Rapid Telephone Triage (ESCORTT) training package on the recognition of stroke across other EMSs in England; and exploring the impact of the early identification of stroke by call handlers on patient and process outcomes. Funding: The National Institute for Health Research Programme Grants for Applied Research programme

On the Use of Gene Ontology Annotations to Assess Functional Similarity among Orthologs and Paralogs: A Short Report

A recent paper (Nehrt et al., PLoS Comput. Biol. 7:e1002073, 2011) has proposed a metric for the “functional similarity” between two genes that uses only the Gene Ontology (GO) annotations directly derived from published experimental results. Applying this metric, the authors concluded that paralogous genes within the mouse genome or the human genome are more functionally similar on average than orthologous genes between these genomes, an unexpected result with broad implications if true. We suggest, based on both theoretical and empirical considerations, that this proposed metric should not be interpreted as a functional similarity, and therefore cannot be used to support any conclusions about the “ortholog conjecture” (or, more properly, the “ortholog functional conservation hypothesis”). First, we reexamine the case studies presented by Nehrt et al. as examples of orthologs with divergent functions, and come to a very different conclusion: they actually exemplify how GO annotations for orthologous genes provide complementary information about conserved biological functions. We then show that there is a global ascertainment bias in the experiment-based GO annotations for human and mouse genes: particular types of experiments tend to be performed in different model organisms. We conclude that the reported statistical differences in annotations between pairs of orthologous genes do not reflect differences in biological function, but rather complementarity in experimental approaches. Our results underscore two general considerations for researchers proposing novel types of analysis based on the GO: 1) that GO annotations are often incomplete, potentially in a biased manner, and subject to an “open world assumption” (absence of an annotation does not imply absence of a function), and 2) that conclusions drawn from a novel, large-scale GO analysis should whenever possible be supported by careful, in-depth examination of examples, to help ensure the conclusions have a justifiable biological basis

PANTHER version 7: improved phylogenetic trees, orthologs and collaboration with the Gene Ontology Consortium

Protein Analysis THrough Evolutionary Relationships (PANTHER) is a comprehensive software system for inferring the functions of genes based on their evolutionary relationships. Phylogenetic trees of gene families form the basis for PANTHER and these trees are annotated with ontology terms describing the evolution of gene function from ancestral to modern day genes. One of the main applications of PANTHER is in accurate prediction of the functions of uncharacterized genes, based on their evolutionary relationships to genes with functions known from experiment. The PANTHER website, freely available at http://www.pantherdb.org, also includes software tools for analyzing genomic data relative to known and inferred gene functions. Since 2007, there have been several new developments to PANTHER: (i) improved phylogenetic trees, explicitly representing speciation and gene duplication events, (ii) identification of gene orthologs, including least diverged orthologs (best one-to-one pairs), (iii) coverage of more genomes (48 genomes, up to 87% of genes in each genome; see http://www.pantherdb.org/panther/summaryStats.jsp), (iv) improved support for alternative database identifiers for genes, proteins and microarray probes and (v) adoption of the SBGN standard for display of biological pathways. In addition, PANTHER trees are being annotated with gene function as part of the Gene Ontology Reference Genome project, resulting in an increasing number of curated functional annotations

Selective adsorption of sulfur dioxide in a robust metal-organic framework material

Selective adsorption of SO2 is realized in a porous metal–organic framework material, and in-depth structural and spectroscopic investigations using X-rays, infrared, and neutrons define the underlying interactions that cause SO2 to bind more strongly than CO2 and N2

Pointing to visible and invisible targets

We investigated how the visibility of targets influenced the type of point used to provide directions. In Study 1 we asked 605 passersby in three localities for directions to well-known local landmarks. When that landmark was in plain view behind the requester, most respondents pointed with their index fingers, and few respondents pointed more than once. In contrast, when the landmark was not in view, respondents pointed initially with their index fingers, but often elaborated with a whole-hand point. In Study 2, we covertly filmed the responses from 157 passersby we approached for directions, capturing both verbal and gestural responses. As in Study 1, few respondents produced more than one gesture when the target was in plain view and initial points were most likely to be index finger points. Thus, in a Western geographical context in which pointing with the index finger is the dominant form of pointing, a slight change in circumstances elicited a preference for pointing with the whole hand when it was the second or third manual gesture in a sequence

The effectiveness, acceptability and cost-effectiveness of psychosocial interventions for maltreated children and adolescents: an evidence synthesis.

BACKGROUND: Child maltreatment is a substantial social problem that affects large numbers of children and young people in the UK, resulting in a range of significant short- and long-term psychosocial problems. OBJECTIVES: To synthesise evidence of the effectiveness, cost-effectiveness and acceptability of interventions addressing the adverse consequences of child maltreatment. STUDY DESIGN: For effectiveness, we included any controlled study. Other study designs were considered for economic decision modelling. For acceptability, we included any study that asked participants for their views. PARTICIPANTS: Children and young people up to 24 years 11 months, who had experienced maltreatment before the age of 17 years 11 months. INTERVENTIONS: Any psychosocial intervention provided in any setting aiming to address the consequences of maltreatment. MAIN OUTCOME MEASURES: Psychological distress [particularly post-traumatic stress disorder (PTSD), depression and anxiety, and self-harm], behaviour, social functioning, quality of life and acceptability. METHODS: Young Persons and Professional Advisory Groups guided the project, which was conducted in accordance with Cochrane Collaboration and NHS Centre for Reviews and Dissemination guidance. Departures from the published protocol were recorded and explained. Meta-analyses and cost-effectiveness analyses of available data were undertaken where possible. RESULTS: We identified 198 effectiveness studies (including 62 randomised trials); six economic evaluations (five using trial data and one decision-analytic model); and 73 studies investigating treatment acceptability. Pooled data on cognitive-behavioural therapy (CBT) for sexual abuse suggested post-treatment reductions in PTSD [standardised mean difference (SMD) -0.44 (95% CI -4.43 to -1.53)], depression [mean difference -2.83 (95% CI -4.53 to -1.13)] and anxiety [SMD -0.23 (95% CI -0.03 to -0.42)]. No differences were observed for post-treatment sexualised behaviour, externalising behaviour, behaviour management skills of parents, or parental support to the child. Findings from attachment-focused interventions suggested improvements in secure attachment [odds ratio 0.14 (95% CI 0.03 to 0.70)] and reductions in disorganised behaviour [SMD 0.23 (95% CI 0.13 to 0.42)], but no differences in avoidant attachment or externalising behaviour. Few studies addressed the role of caregivers, or the impact of the therapist-child relationship. Economic evaluations suffered methodological limitations and provided conflicting results. As a result, decision-analytic modelling was not possible, but cost-effectiveness analysis using effectiveness data from meta-analyses was undertaken for the most promising intervention: CBT for sexual abuse. Analyses of the cost-effectiveness of CBT were limited by the lack of cost data beyond the cost of CBT itself. CONCLUSIONS: It is not possible to draw firm conclusions about which interventions are effective for children with different maltreatment profiles, which are of no benefit or are harmful, and which factors encourage people to seek therapy, accept the offer of therapy and actively engage with therapy. Little is known about the cost-effectiveness of alternative interventions. LIMITATIONS: Studies were largely conducted outside the UK. The heterogeneity of outcomes and measures seriously impacted on the ability to conduct meta-analyses. FUTURE WORK: Studies are needed that assess the effectiveness of interventions within a UK context, which address the wider effects of maltreatment, as well as specific clinical outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003889. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Binarity and multiperiodicity in high-amplitude delta Scuti stars

We have carried out a photometric and spectroscopic survey of bright high-amplitude delta Scuti (HADS) stars. The aim was to detect binarity and multiperiodicity (or both) in order to explore the possibility of combining binary star astrophysics with stellar oscillations. Here we present the first results for ten, predominantly southern, HADS variables. We detected the orbital motion of RS Gru with a semi-amplitude of ~6.5 km/s and 11.5 days period. The companion is inferred to be a low-mass dwarf star in a close orbit around RS Gru. We found multiperiodicity in RY Lep both from photometric and radial velocity data and detected orbital motion in the radial velocities with hints of a possible period of 500--700 days. The data also revealed that the amplitude of the secondary frequency is variable on the time-scale of a few years, whereas the dominant mode is stable. Radial velocities of AD CMi revealed cycle-to-cycle variations which might be due to non-radial pulsations. We confirmed the multiperiodic nature of BQ Ind, while we obtained the first radial velocity curves of ZZ Mic and BE Lyn. The radial velocity curve and the O-C diagram of CY Aqr are consistent with the long-period binary hypothesis. We took new time series photometry on XX Cyg, DY Her and DY Peg, with which we updated their O-C diagrams.Comment: 15 pages, 16 pages, accepted for publication in MNRA

Particle suspension reactors and materials for solar-driven water splitting

Reactors based on particle suspensions for the capture, conversion, storage, and use of solar energy as H_2 are projected to be cost-competitive with fossil fuels. In light of this, this review paper summarizes state-of-the-art particle light absorbers and cocatalysts as suspensions (photocatalysts) that demonstrate visible-light-driven water splitting on the laboratory scale. Also presented are reactor descriptions, theoretical considerations particular to particle suspension reactors, and efficiency and performance characterization metrics. Opportunities for targeted research, analysis, and development of reactor designs are highlighted