COordination of Standards in MetabOlomicS (COSMOS): facilitating integrated metabolomics data access

Metabolomics has become a crucial phenotyping technique in a range of research fields including medicine, the life sciences, biotechnology and the environmental sciences. This necessitates the transfer of experimental information between research groups, as well as potentially to publishers and funders. After the initial efforts of the metabolomics standards initiative, minimum reporting standards were proposed which included the concepts for metabolomics databases. Built by the community, standards and infrastructure for metabolomics are still needed to allow storage, exchange, comparison and re-utilization of metabolomics data. The Framework Programme 7 EU Initiative ‘coordination of standards in metabolomics’ (COSMOS) is developing a robust data infrastructure and exchange standards for metabolomics data and metadata. This is to support workflows for a broad range of metabolomics applications within the European metabolomics community and the wider metabolomics and biomedical communities’ participation. Here we announce our concepts and efforts asking for re-engagement of the metabolomics community, academics and industry, journal publishers, software and hardware vendors, as well as those interested in standardisation worldwide (addressing missing metabolomics ontologies, complex-metadata capturing and XML based open source data exchange format), to join and work towards updating and implementing metabolomics standards

Evaluation of the effects of implementing an electronic early warning score system: protocol for a stepped wedge study

Background: An Early Warning Score is a clinical risk score based upon vital signs intended to aid recognition of patients in need of urgent medical attention. The use of an escalation of care policy based upon an Early Warning Score is mandated as the standard of practice in British hospitals. Electronic systems for recording vital sign observations and Early Warning Score calculation offer theoretical benefits over paper-based systems. However, the evidence for their clinical benefit is limited. Previous studies have shown inconsistent results. The majority have employed a “before and after” study design, which may be strongly confounded by simultaneously occurring events. This study aims to examine how the implementation of an electronic early warning score system, System for Notification and Documentation (SEND), affects the recognition of clinical deterioration occurring in hospitalised adult patients. Methods: This study is a non-randomised stepped wedge evaluation carried out across the four hospitals of the Oxford University Hospitals NHS Trust, comparing charting on paper and charting using SEND. We assume that more frequent monitoring of acutely ill patients is associated with better recognition of patient deterioration. The primary outcome measure is the time between a patient’s first observations set with an Early Warning Score above the alerting threshold and their subsequent set of observations. Secondary outcome measures are in-hospital mortality, cardiac arrest and Intensive Care admission rates, hospital length of stay and system usability measured using the System Usability Scale. We will also measure Intensive Care length of stay, Intensive Care mortality, Acute Physiology and Chronic Health Evaluation (APACHE) II acute physiology score on admission, to examine whether the introduction of SEND has any effect on Intensive Care-related outcomes. Discussion: The development of this protocol has been informed by guidance from the Agency for Healthcare Research and Quality (AHRQ) Health Information Technology Evaluation Toolkit and Delone and McLeans’s Model of Information System Success. Our chosen trial design, a stepped wedge study, is well suited to the study of a phased roll out. The choice of primary endpoint is challenging. We have selected the time from the first triggering observation set to the subsequent observation set. This has the benefit of being easy to measure on both paper and electronic charting and having a straightforward interpretation. We have collected qualitative measures of system quality via a user questionnaire and organisational descriptors to help readers understand the context in which SEND has been implemented

Long-term follow-up of patients undergoing free tissue transfer to the lower limb following trauma

Background Free flap transfer reconstruction following severe lower limb trauma has become an increasingly used tool over the past four decades. However, little is known about the long-term outcome of these complex and costly procedures. The aim of this work is to assess the long-term outcomes in patients undergoing free flap transfer reconstruction of Gustillo IIIB lower limb injuries at the John Radcliffe Hospital, Oxford (UK). Methods Forty-two potential participants were identified and contacted after review of operation records between 1990 and 2000. Physical and psychosocial outcomes were assessed using SIP, WOMAC and study-specific questionnaires. Results Eighteen participants responded, with a median follow-up time of 14 years since reconstruction. Road traffic collisions were the most common cause of trauma (12/18). The majority of participants (13/18) had SIP physical and psychosocial sub-scores equivalent to the general population (<5), and half the participants reported normal function in the study specific questionnaire (9/18). Two participants reported SIP physical sub-scores of ≥20, implying severe physical disability, associated with higher pain and stiffness scores in the WOMAC and study-specific questionnaire. Conclusions The participants considered in this cohort generally have excellent long-term outcomes, in terms of function, aesthetic appearance and psychosocial well-being. The cohort presented here sets a standard by which other long-term studies can be measured

Effects of infant cleft lip on adult gaze and perceptions of ‘cuteness'

Objective: Early mother-infant interactions are impaired in the context of infant cleft lip, and are associated with adverse child psychological outcomes, but the nature of these interaction difficulties is not yet fully understood. The aim of this study was to explore adult gaze behaviour and cuteness perception, which are particularly important during early social exchanges, in response to infants with cleft lip, in order to investigate potential foundations for the interaction difficulties seen in this population. Methods: Using an eye-tracker, eye movements were recorded as adult participants viewed images of infant faces with and without cleft lip. Participants also rated each infant on a scale of cuteness. Results: Participants fixated significantly longer on the mouths of infants with cleft lip, which occurred at the expense of fixation on eyes. Severity of cleft lip was associated with the strength of fixation bias, with participants looking even longer at the mouths of infants with the most severe clefts. Infants with cleft lip were rated as significantly less cute than unaffected infants. Men rated infants as less cute than women overall, but gave particularly low ratings to infants with cleft lip Conclusions: Results demonstrate that the limited disturbance in infant facial configuration of cleft lip can significantly alter adult gaze patterns and cuteness perception. Our findings could have important implications for early interactions, and may help in the development of interventions to foster healthy development in infants with cleft lip

Psychometric findings and normative values for the CLEFT-Q based on 2434 children and young adult patients with cleft lip and/or palate from 12 countries

BACKGROUND: Patients with cleft lip and/or palate can undergo numerous procedures to improve appearance, speech, dentition and hearing. We developed a cleft-specific patient-reported outcome instrument to facilitate rigorous international measurement and benchmarking. METHODS: Data were collected from patients aged 8-29 years with cleft lip and/or palate at 30 hospitals in 12 countries between October 2014 and November 2016. Rasch measurement theory analysis was used to refine the scales and to examine reliability and validity. Normative CLEFT-Q values were computed for age, sex and cleft type. RESULTS: Analysis led to the refinement of an eating and drinking checklist and 12 scales measuring appearance (of the face, nose, nostrils, teeth, lips, jaws and cleft lip scar), health-related quality of life (psychological, social, school, speech distress) and speech function. All scales met the requirements of the Rasch model. Analysis to explore differential item functioning by age, sex and country provided evidence to support the use of a common scoring algorithm for each scale for international use. Lower (worse) scores on CLEFT-Q scales were associated with having a speech problem, being unhappy with facial appearance, and needing future cleft-related treatments, providing evidence of construct validity. Normative values for age, sex and cleft type showed poorer outcomes associated with older age, female sex and having a visible cleft. INTERPRETATION: The CLEFT-Q represents a rigorously developed instrument that can be used internationally to collect and compare evidence-based outcomes data from patients aged 8-29 years of age with cleft lip and/or palate

TD/GC–MS analysis of volatile markers emitted from mono- and co-cultures of Enterobacter cloacae and Pseudomonas aeruginosa in artificial sputum

Introduction: Infections such as ventilator-associated pneumonia (VAP) can be caused by one or more pathogens. Current methods for identifying these pathogenic microbes often require invasive sampling, and can be time consuming, due to the requirement for prolonged cultural enrichment along with selective and differential plating steps. This results in delays in diagnosis which in such critically ill patients can have potentially life-threatening consequences. Therefore, a non-invasive and timely diagnostic method is required. Detection of microbial volatile organic compounds (VOCs) in exhaled breath is proposed as an alternative method for identifying these pathogens and may distinguish between mono- and poly-microbial infections. Objectives: To investigate volatile metabolites that discriminate between bacterial mono- and co-cultures. Methods: VAP-associated pathogens Enterobacter cloacae and Pseudomonas aeruginosa were cultured individually and together in artificial sputum medium for 24 h and their headspace was analysed for potential discriminatory VOCs by thermal desorption gas chromatography–mass spectrometry. Results: Of the 70 VOCs putatively identified, 23 were found to significantly increase during bacterial culture (i.e. likely to be released during metabolism) and 13 decreased (i.e. likely consumed during metabolism). The other VOCs showed no transformation (similar concentrations observed as in the medium). Bacteria-specific VOCs including 2-methyl-1-propanol, 2-phenylethanol, and 3-methyl-1-butanol were observed in the headspace of axenic cultures of E. cloacae, and methyl 2-ethylhexanoate in the headspace of P. aeruginosa cultures which is novel to this investigation. Previously reported VOCs 1-undecene and pyrrole were also detected. The metabolites 2-methylbutyl acetate and methyl 2-methylbutyrate, which are reported to exhibit antimicrobial activity, were elevated in co-culture only. Conclusion: The observed VOCs were able to differentiate axenic and co-cultures. Validation of these markers in exhaled breath specimens could prove useful for timely pathogen identification and infection type diagnosis

Fine-mapping and candidate gene investigation within the PARK10 locus

Herein, we investigate whether single-nucleotide polymorphisms (SNPs) across the PARK10 locus are associated with susceptibility to Parkinson's disease (PD) or age at onset (AAO) of disease. One hundred and eighty-eight SNPs were genotyped across the PARK10 locus in 180 PD patients and 180 controls from central Norway (stage 1). We then used the linkage disequilibrium (LD) structure from stage 1 to select 75 SNPs for genotyping in 186 patients and 186 controls from Ireland (stage 2). Nineteen SNPs were selected from this and previous studies for follow-up in an extended Norwegian series (530 patients and 1142 controls), the Irish series and a US series (221 patients and 221 controls) (stage 3). After correction for multiple testing, markers within ubiquitin specific peptidase 24 (USP24) are significantly associated with PD within Norwegian, Irish, and US series combined (rs13312: odds ratio (OR) 0.78, P<0.001; rs487230: OR 0.80, P=0.001). Independently, the association for rs13312 is strongest in the extended Norwegian series (OR 0.76, P=0.005), although not significant after correction for multiple testing (P≤0.003 is considered significant). ORs in the Irish series are almost identical, and a similar but a weaker effect was observed for the US series. No marker showed consistent association with AAO. Our data indicate that genetic variability in USP24 is associated with PD. Although our work extends and confirms a previous report, the observed effect size does not explain the PARK10 linkage peak