Optimizing the use of electronic medical records for large scale research in psychiatry

The explosion and abundance of digital data could facilitate large scale research for psychiatry and mental health. Research using so-called “real world data” – such as electronic medical/health records – can be resource-efficient, facilitate rapid hypothesis generation and testing, complement existing evidence (e.g. from trials and evidence-synthesis) and may enable a route to translate evidence into clinically effective, outcomes-driven care for patient populations that may be under-represented. However, the interpretation and processing of real world data sources is complex because the clinically important ‘signal’ is often contained in both structured and unstructured (narrative or “free-text”) data. Techniques for extracting meaningful information (signal) from unstructured text exist and have advanced the re-use of routinely collected clinical data but these techniques require cautious evaluation. In this paper, we survey the opportunities, risks and progress made in the use of electronic medical record (real world) data for psychiatric research

Modelling rotational failure in confined geometries using DLO

Discontinuity layout optimisation (DLO) is a generally applicable numerical limit analysis procedure that can be used to identify critical plastic collapse mechanisms in engineering problems. Considering the modelling of in-plane failure, the authors have previously presented a formulation capable of identifying rotational failure mechanisms in non-dilating media. However, the formulation presented did not explicitly address cases involving confined geometries, where curved slip lines could potentially intersect boundaries. In this paper, methods are outlined which permit efficient modelling of such cases. Details of the kinematic and equilibrium formulations are provided, which are then verified through application to various geotechnical and structural mechanics problems. It is shown that results of high accuracy can be obtained, both in terms of the predicted collapse load and the corresponding failure mechanism

Mathematical models of magnetospheric convection and its coupling to the ionosphere

Mathematical models of magnetospheric convection and its coupling to ionospher

Effect of Covid-19 Vaccination on Transmission of Alpha and Delta Variants

BACKGROUND: Before the emergence of the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccination reduced transmission of SARS-CoV-2 from vaccinated persons who became infected, potentially by reducing viral loads. Although vaccination still lowers the risk of infection, similar viral loads in vaccinated and unvaccinated persons who are infected with the delta variant call into question the degree to which vaccination prevents transmission. METHODS: We used contact-testing data from England to perform a retrospective observational cohort study involving adult contacts of SARS-CoV-2–infected adult index patients. We used multivariable Poisson regression to investigate associations between transmission and the vaccination status of index patients and contacts and to determine how these associations varied with the B.1.1.7 (alpha) and delta variants and time since the second vaccination. RESULTS: Among 146,243 tested contacts of 108,498 index patients, 54,667 (37%) had positive SARS-CoV-2 polymerase-chain-reaction (PCR) tests. In index patients who became infected with the alpha variant, two vaccinations with either BNT162b2 or ChAdOx1 nCoV-19 (also known as AZD1222), as compared with no vaccination, were independently associated with reduced PCR positivity in contacts (adjusted rate ratio with BNT162b2, 0.32; 95% confidence interval [CI], 0.21 to 0.48; and with ChAdOx1 nCoV-19, 0.48; 95% CI, 0.30 to 0.78). Vaccine-associated reductions in transmission of the delta variant were smaller than those with the alpha variant, and reductions in transmission of the delta variant after two BNT162b2 vaccinations were greater (adjusted rate ratio for the comparison with no vaccination, 0.50; 95% CI, 0.39 to 0.65) than after two ChAdOx1 nCoV-19 vaccinations (adjusted rate ratio, 0.76; 95% CI, 0.70 to 0.82). Variation in cycle-threshold (Ct) values (indicative of viral load) in index patients explained 7 to 23% of vaccine-associated reductions in transmission of the two variants. The reductions in transmission of the delta variant declined over time after the second vaccination, reaching levels that were similar to those in unvaccinated persons by 12 weeks in index patients who had received ChAdOx1 nCoV-19 and attenuating substantially in those who had received BNT162b2. Protection in contacts also declined in the 3-month period after the second vaccination. CONCLUSIONS: Vaccination was associated with a smaller reduction in transmission of the delta variant than of the alpha variant, and the effects of vaccination decreased over time. PCR Ct values at diagnosis of the index patient only partially explained decreased transmission. (Funded by the U.K. Government Department of Health and Social Care and others.

Pulling together: keeping track of pedagogy, design and evaluation through the development of scenarios: a case study

This case study describes the multipurpose use of scenarios in a large multinational research project (MOBIlearn) whose aims are to design and develop a pedagogically sound mobile learning environment. Maintaining effective communication and design focus in large consortia is a wellknown problem (see Carroll, 2000), and we describe the role of scenarios in addressing this. Scenarios were initially used to simply envision the future system in order to inform design, but as the project progressed, the role of the scenarios grew to encompass (i) relating system design and implementation to pedagogy by providing a common frame of reference for developers and pedagogic experts; (ii) through a process of refinement, defining the evaluation strategy for the user trials; and (iii) allowing us to keep the user at the heart of the development project. Thus, scenarios helped to resolve the difficulty identified by Taylor (2004) of how to bring together the relatively high level issues of pedagogic evaluation and the more technical user-centred system evaluation. The development of a first-aid training scenario is used as an illustrative example

Digital PCR methods improve detection sensitivity and measurement precision of low abundance mtDNA deletions

Mitochondrial DNA (mtDNA) mutations are a common cause of primary mitochondrial disorders, and have also been implicated in a broad collection of conditions, including aging, neurodegeneration, and cancer. Prevalent among these pathogenic variants are mtDNA deletions, which show a strong bias for the loss of sequence in the major arc between, but not including, the heavy and light strand origins of replication. Because individual mtDNA deletions can accumulate focally, occur with multiple mixed breakpoints, and in the presence of normal mtDNA sequences, methods that detect broad-spectrum mutations with enhanced sensitivity and limited costs have both research and clinical applications. In this study, we evaluated semi-quantitative and digital PCR-based methods of mtDNA deletion detection using double-stranded reference templates or biological samples. Our aim was to describe key experimental assay parameters that will enable the analysis of low levels or small differences in mtDNA deletion load during disease progression, with limited false-positive detection. We determined that the digital PCR method significantly improved mtDNA deletion detection sensitivity through absolute quantitation, improved precision and reduced assay standard error

Bistability in Apoptosis by Receptor Clustering

Apoptosis is a highly regulated cell death mechanism involved in many physiological processes. A key component of extrinsically activated apoptosis is the death receptor Fas, which, on binding to its cognate ligand FasL, oligomerize to form the death-inducing signaling complex. Motivated by recent experimental data, we propose a mathematical model of death ligand-receptor dynamics where FasL acts as a clustering agent for Fas, which form locally stable signaling platforms through proximity-induced receptor interactions. Significantly, the model exhibits hysteresis, providing an upstream mechanism for bistability and robustness. At low receptor concentrations, the bistability is contingent on the trimerism of FasL. Moreover, irreversible bistability, representing a committed cell death decision, emerges at high concentrations, which may be achieved through receptor pre-association or localization onto membrane lipid rafts. Thus, our model provides a novel theory for these observed biological phenomena within the unified context of bistability. Importantly, as Fas interactions initiate the extrinsic apoptotic pathway, our model also suggests a mechanism by which cells may function as bistable life/death switches independently of any such dynamics in their downstream components. Our results highlight the role of death receptors in deciding cell fate and add to the signal processing capabilities attributed to receptor clustering.Comment: Accepted by PLoS Comput Bio

The impact of non-severe burn injury on cardiac function and long-term cardiovascular pathology

Severe burn injury significantly affects cardiovascular function for up to 3 years. However, whether this leads to long-term pathology is unknown. The impact of non-severe burn injury, which accounts for over 80% of admissions in developed countries, has not been investigated. Using a rodent model of non-severe burn injury with subsequent echocardiography we showed significantly increased left ventricular end systolic diameter (LVESD) and ventricular wall thickness at up to 3 months post-injury. Use of propranolol abrogated the changes in cardiac measures observed. Subsequently we investigated changes in a patient cohort with non-severe injury. Echocardiography measured at baseline and at 3 months post-injury showed increased LVESD at 3 months and significantly decreased posterior wall diameter. Finally, 32 years of Western Australian hospital records were used to investigate the incidence of cardiovascular disease admissions after burn injury. People who had experienced a burn had increased hospital admissions and length of stay for cardiovascular diseases when compared to a matched uninjured cohort. This study presents animal, patient and population data that strongly suggest non-severe burn injury has significant effects on cardiovascular function and long-term morbidity in some burn patients. Identification of patients at risk will promote better intervention and outcomes for burn patients