Why democratize bioinformatics?

Network bioinformatics and web-based data collection instruments have the capacity to improve the efficiency of the UK’s appropriately high levels of investment into cardiovascular research. A very large proportion of scientific data falls into the long-tail of the cardiovascular research distribution curve, with numerous small independent research efforts yielding a rich variety of specialty data sets. The merging of such myriad datasets and the eradication of data silos, plus linkage with outcomes could be greatly facilitated through the provision of a national set of standardised data collection instruments—a shared-cardioinformatics library of tools designed by and for clinical academics active in the long-tail of biomedical research. Across the cardiovascular research domain, like the rest of medicine, the national aggregation and democratization of diverse long-tail data is the best way to convert numerous small but expensive cohort data sources into big data, expanding our knowledge-base, breaking down translational barriers, improving research efficiency and with time, improving patient outcomes

Arteriography during ex vivo renal perfusion A complication

A case of bilateral renal-cell carcinoma unsuccessfully treated with bench surgery is reported. The reason for failure was apparently the toxicity of the contrast media used during the ex vivo arteriographic studies. © 1973

Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

‘Not a country at all’: landscape and Wuthering Heights

This article explores the issue of women’s representational genealogies through an analysis of Andrea Arnold’s 2011 Wuthering Heights. Beginning with 1970s feminist arguments for a specifically female literary tradition, it argues that running through both these early attempts to construct an alternative female literary tradition and later work in feminist philosophy, cultural geography and film history is a concern with questions of ‘alternative landscapes’: of how to represent, and how to encounter, space differently. Adopting Mary Jacobus’ notion of intertextual ‘correspondence’ between women’s texts, and taking Arnold’s film as its case study, it seeks to trace some of the intertextual movements – the reframings, deframings and spatial reorderings – that link Andrea Arnold’s film to Emily Brontë’s original novel. Focusing on two elements of her treatment of landscape – her use of ‘unframed’ landscape and her focus on visceral textural detail – it points to correspondences in other women’s writing, photography and film-making. It argues that these intensely tactile close-up sequences which puncture an apparently realist narrative constitute an insistent presence beneath, or within, the ordered framing which is our more usual mode of viewing landscape. As the novel Wuthering Heights is unmade in Arnold’s adaptation and its framings ruptured, it is through this disturbance of hierarchies of time, space and landscape that we can trace the correspondences of an alternative genealogy

Intelligent audio plugin framework for the Web Audio API

The Web Audio API introduced native audio processing into web browsers. Audio plugin standards have been created for developers to create audio-rich processors and deploy them into media rich websites. It is critical these standards support flexible designs with clear host-plugin interaction to ease integration and avoid non-standard plugins. Intelligent features should be embedded into standards to help develop next-generation interfaces and designs. This paper presents a discussion on audio plugins in the web audio API, how they should behave and leverage web technologies with an overview of current standards

High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a stepped-wedge, cluster-randomised controlled trial.

BACKGROUND: High-sensitivity cardiac troponin assays permit use of lower thresholds for the diagnosis of myocardial infarction, but whether this improves clinical outcomes is unknown. We aimed to determine whether the introduction of a high-sensitivity cardiac troponin I (hs-cTnI) assay with a sex-specific 99th centile diagnostic threshold would reduce subsequent myocardial infarction or cardiovascular death in patients with suspected acute coronary syndrome. METHODS: In this stepped-wedge, cluster-randomised controlled trial across ten secondary or tertiary care hospitals in Scotland, we evaluated the implementation of an hs-cTnI assay in consecutive patients who had been admitted to the hospitals' emergency departments with suspected acute coronary syndrome. Patients were eligible for inclusion if they presented with suspected acute coronary syndrome and had paired cardiac troponin measurements from the standard care and trial assays. During a validation phase of 6-12 months, results from the hs-cTnI assay were concealed from the attending clinician, and a contemporary cardiac troponin I (cTnI) assay was used to guide care. Hospitals were randomly allocated to early (n=5 hospitals) or late (n=5 hospitals) implementation, in which the high-sensitivity assay and sex-specific 99th centile diagnostic threshold was introduced immediately after the 6-month validation phase or was deferred for a further 6 months. Patients reclassified by the high-sensitivity assay were defined as those with an increased hs-cTnI concentration in whom cTnI concentrations were below the diagnostic threshold on the contemporary assay. The primary outcome was subsequent myocardial infarction or death from cardiovascular causes at 1 year after initial presentation. Outcomes were compared in patients reclassified by the high-sensitivity assay before and after its implementation by use of an adjusted generalised linear mixed model. This trial is registered with ClinicalTrials.gov, number NCT01852123. FINDINGS: Between June 10, 2013, and March 3, 2016, we enrolled 48 282 consecutive patients (61 [SD 17] years, 47% women) of whom 10 360 (21%) patients had cTnI concentrations greater than those of the 99th centile of the normal range of values, who were identified by the contemporary assay or the high-sensitivity assay. The high-sensitivity assay reclassified 1771 (17%) of 10 360 patients with myocardial injury or infarction who were not identified by the contemporary assay. In those reclassified, subsequent myocardial infarction or cardiovascular death within 1 year occurred in 105 (15%) of 720 patients in the validation phase and 131 (12%) of 1051 patients in the implementation phase (adjusted odds ratio for implementation vs validation phase 1·10, 95% CI 0·75 to 1·61; p=0·620). INTERPRETATION: Use of a high-sensitivity assay prompted reclassification of 1771 (17%) of 10 360 patients with myocardial injury or infarction, but was not associated with a lower subsequent incidence of myocardial infarction or cardiovascular death at 1 year. Our findings question whether the diagnostic threshold for myocardial infarction should be based on the 99th centile derived from a normal reference population. FUNDING: The British Heart Foundation

Allocating Unique Property Reference Numbers to Patient Addresses Using A Deterministic Address-Matching Algorithm: Evaluation of Accuracy, Match Rate and Bias

Conference Proceedings from International Population Data Linkage Conference 202