OAK (Online Access to Knowledge) Commons (Young Harris College)
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Unintended consequences of patient online access to health records: a qualitative study in UK primary care
No full textAre we leaving money on the table in infertility RCTs? Trialists should statistically adjust for prespecified, prognostic covariates to increase power.
No full textInfertility RCTs are often too small to detect realistic treatment effects. Large observational studies have been proposed as a solution. However, this strategy threatens to weaken the evidence base further, because non-random assignment to treatments makes it impossible to distinguish effects of treatment from confounding factors. Alternative solutions are required. Power in an RCT can be increased by adjusting for prespecified, prognostic covariates when performing statistical analysis, and if stratified randomization or minimization has been used, it is essential to adjust in order to get the correct answer. We present data showing that this simple, free, and frequently necessary strategy for increasing power is seldom employed, even in trials appearing in leading journals. We use this to motivate a pedagogical discussion and provide a worked example. While covariate adjustment can’t solve the problem of underpowered trials outright, there is an imperative to use sound methodology to maximize the information each trial yields
Adrenergic prolongation of action potential duration in rainbow trout myocardium via inhibition of the delayed rectifier potassium current, IKr.
No full textCatecholamines mediate the ‘fight or flight’ response in a wide variety of vertebrates.The endogenous catecholamine adrenaline increases heart rate and contractilestrength to raise cardiac output. The increase in contractile force is driven in large partby an increase in myocyte Ca 2+ influx on the L-type Ca current (I CaL ) during thecardiac action potential (AP). Here, we report a K + - based mechanism that prolongsAP duration (APD) in fish hearts following adrenergic stimulation. We show thatadrenergic stimulation inhibits the delayed rectifier K + current (I Kr ) in rainbow trout( Oncorhynchus mykiss ) cardiomyocytes. This slows repolarization and prolongsAPD which may contribute to positive inotropy following adrenergic stimulation in fishhearts. The endogenous ligand, adrenaline (10 -6 M), which activates both α- and βARs reduced maximal I Kr tail current to 61.4±3.9% of control in atrial and ventricularmyocytes resulting in an APD prolongation of ~ 20% at both 50 and 90%repolarization. This effect was reproduced by the α-specific adrenergic agonist,phenylephrine (10 -6 M), but not the β-specific adrenergic agonist isoproterenol (10 -6 M). Adrenaline (10 -6 M) in the presence of β 1 and β 2 -blockers (10 -6 Matenolol and 10 -6 M ICI-118551, respectively) also inhibited I Kr . Thus, I Krsuppression following adrenergic stimulation leads to APD prolongation in the rainbowtrout heart. This is the first time this mechanism has been identified in fish and may actin unison with the well-known enhancement of I CaL following adrenergic stimulationto prolong APD and increase cardiac inotropy
Enhanced biosynthesis of Polyhydroxyalkanoates by continuous feeding of volatile fatty acids in Haloferax mediterranei
No full textIn this work, the biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) in Haloferax mediterranei was enhanced by continuous feeding of volatile fatty acids. Using this strategy, polymer production was doubled to around 5 g L–1 PHBV when compared to pulse-fed fed-batch fermentations. Polymer productivity and yield increased up to 12.8 mg L–1 h–1 and 0.63 g g–1 respectively when the carbon concentration in the fermentation media was kept constant at 0.25 molar. This biopolymer production was achieved in less than half the time when compared to pulse feeding, effectively quadrupling the overall PHA productivity. Control over co-polymer composition was achieved and maintained at around 40 mol% 3-hydroxyvalerate (3HV). A correlation between substrate consumption and cell growth was observed, providing a crucial tool for feeding rate selection in future fermentations. The higher productivity and yield obtained with the novel feeding strategy will be key to future industrial scale PHA production
Hybrid Autoregressive Inference for Scalable Multi-hop Explanation Regeneration
No full textRegenerating natural language explanations in the scientific domain has been proposed as a benchmark to evaluate complex multi-hop and explainable inference. In this context, large language models can achieve state-of-the-art performance when employed as cross-encoder architectures and fine-tuned on human-annotated explanations. However, while much attention has been devoted to the quality of the explanations, the problem of performing inference efficiently is largely under-studied. Cross-encoders, in fact, are intrinsically not scalable, possessing limited applicability to real world scenarios that require inference on massive facts banks.To enable complex multi-hop reasoning at scale, this paper focuses on bi-encoder architectures, investigating the problem of scientific explanation regeneration at the intersection of dense and sparse models. Specifically, we present SCAR (for Scalable Autoregressive Inference), a hybrid framework that iteratively combines a Transformer-based bi-encoder with a sparse model of explanatory power, designed to leverage explicit inference patterns in the explanations. Our experiments demonstrate that the hybrid framework significantly outperforms previous sparse models, achieving performance comparable with that of state-of-the-art cross-encoders while being ≈ 50 times faster and scalable to corpora of millions of facts. Further analyses on semantic drift and multi-hop question answering reveal that the proposed hybridisation boosts the quality of the most challenging explanations, contributing to improved performance on downstream inference tasks
Evaluation of two-year recall of self-reported pesticide exposure among Ugandan smallholder farmers
No full textObjectives: To evaluate smallholder farmers’ recall of pesticide use and exposure determinants over a two-year period in a low-income country context. Methods: The Pesticide Use in Tropical Settings (PESTROP) study in Uganda consists of 302 smallholder farmers who were interviewed in 2017. In the same season in 2019, these farmers were re-questioned concerning pesticide use (e.g., use of active ingredients) and exposure information (e.g., crops, personal protective equipment [PPE], hygienic behaviours) they had previously provided. The extent of recall bias was assessed by comparing responses at follow-up in 2019 with practices and behaviours reported from the baseline interview in 2017.Results: An 84% (n=255) follow-up response rate was attained. We found instances of better recall (e.g., overall agreement >70% and Area Under the Curve (AUC) values >0.7) for the use of some active ingredients, commonly used PPE items, and washing clothes after application, whereas only 13.3% could correctly recall their three major crops. We observed a trend where more individuals reported the use of active ingredients, while fewer reported the use of PPE items, two years later. In general, we found better agreement in the recall of years working with pesticides compared to hours per day or days per week in the field, with no apparent systematic over or under reporting by demographic characteristics. Conclusions: While some of these findings provide consistency with those from high-income countries, more research is needed on recall in poorly educated agriculture communities in low- and middle-income settings to confirm these results
Comparison of biomedical relationship extraction methods and models for knowledge graph creation
No full textBiomedical research is growing at such an exponential pace that scientists, researchers, and practitioners are no more able to cope with the amount of published literature in the domain. The knowledge presented in the literature needs to be systematized in such a way that claims and hypotheses can be easily found, accessed, and validated. Knowledge graphs can provide such a framework for semantic knowledge representation from literature. However, in order to build a knowledge graph, it is necessary to extract knowledge as relationships between biomedical entities and normalize both entities and relationship types. In this paper, we present and compare a few rule-based and machine learning-based (Naive Bayes, Random Forests as examples of traditional machine learning methods and DistilBERT, PubMedBERT, T5, and SciFive-based models as examples of modern deep learning transformers) methods for scalable relationship extraction from biomedical literature, and for the integration into the knowledge graphs. We examine how resilient are these various methods to unbalanced and fairly small datasets. Our experiments show that transformer-based models handle well both small (due to pre-training on a large dataset) and unbalanced datasets. The best performing model was the PubMedBERT-based model fine-tuned on balanced data, with a reported F1-score of 0.92. The distilBERT-based model followed with an F1-score of 0.89, performing faster and with lower resource requirements. BERT-based models performed better than T5-based generative models
Educational psychologists’ use of cognitive behavioural therapy in professional practice
No full textAim: There is increasing recognition of the centrality schools have in supporting children and young people’s mental health and wellbeing, and the role of educational psychologists (EPs) in supporting this. Cognitive behavioural therapy (CBT) is a frequently-used, evidence-based approach for supporting a range of outcomes. The purpose of this study is to explore how EPs are operationalising CBT in their practice, and which therapeutic competencies are demonstrated. Method: Semi-structured interviews were completed with a self-selecting sample of eight EPs reporting to be knowledgeable about CBT and to regularly use it in their practice. Transcribed data were analysed using inductive and deductive thematic analysis. Findings: Key themes related to CBT in applied practice, the EP role, drawing on other psychological approaches, ethical practice, external influences and having a holistic view of the child. EPs were using CBT across a continuum of formality in therapeutic work and multi-faceted casework. A range of CBT competencies was demonstrated in practice with children and young people, and adults. Limitations: As an exploratory research study the sample size was very small. The self-selecting sample does not claim to be representative of the wider EP population. The extent to which findings enable an understanding of the effectiveness of CBT within wider EP practice is extremely limited. Conclusions: The flexibility of CBT as a therapeutic modality gives insight into its potential wider contribution across EP practice. Potential implications for EP professional training and practice are considered
Long-term antibody response following COVID-19 vaccination in patients receiving peritoneal dialysis
No full textMitochondrial antiviral-signalling protein is a client of the BAG6 protein quality control complex
No full textThe heterotrimeric BAG6 complex coordinates the direct handover of newly synthesised tail-anchored (TA) membrane proteins from an SGTA-bound preloading complex to the endoplasmic reticulum (ER) delivery component TRC40. In contrast, defective precursors, including aberrant TA proteins, form a stable complex with this cytosolic protein quality control factor, enabling such clients to be either productively re-routed or selectively degraded. We identify the mitochondrial TA protein MAVS (mitochondrial antiviral-signalling protein) as an endogenous client of both SGTA and the BAG6 complex. Our data suggest that the BAG6 complex binds to a cytosolic pool of MAVS before its misinsertion into the ER membrane, from where it can subsequently be removed via ATP13A1-mediated dislocation. This BAG6- associated fraction of MAVS is dynamic and responds to the activation of an innate immune response, suggesting that BAG6 may modulate the pool of MAVS that is available for coordinating the cellular response to viral infection