101 research outputs found

    Situationally-sensitive knowledge translation and relational decision making in hyperacute stroke: a qualitive study

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    Stroke is a leading cause of disability. Early treatment of acute ischaemic stroke with rtPA reduces the risk of longer term dependency but carries an increased risk of causing immediate bleeding complications. To understand the challenges of knowledge translation and decision making about treatment with rtPA in hyperacute stroke and hence to inform development of appropriate decision support we interviewed patients, their family and health professionals. The emergency setting and the symptomatic effects of hyper-acute stroke shaped the form, content and manner of knowledge translation to support decision making. Decision making about rtPA in hyperacute stroke presented three conundrums for patients, family and clinicians. 1) How to allow time for reflection in a severely time-limited setting. 2) How to facilitate knowledge translation regarding important treatment risks and benefits when patient and family capacity is blunted by the effects and shock of stroke. 3) How to ensure patient and family views are taken into account when the situation produces reliance on the expertise of clinicians. Strategies adopted to meet these conundrums were fourfold: face to face communication; shaping decisions; incremental provision of information; and communication tailored to the individual patient. Relational forms of interaction were understood to engender trust and allay anxiety. Shaping decisions with patients was understood as an expression of confidence by clinicians that helped alleviate anxiety and offered hope and reassurance to patients and their family experiencing the shock of the stroke event. Neutral presentations of information and treatment options promoted uncertainty and contributed to anxiety. ‘Drip feeding’ information created moments for reflection: clinicians literally made time. Tailoring information to the particular patient and family situation allowed clinicians to account for social and emotional contexts. The principal responses to the challenges of decision making about rtPA in hyperacute stroke were relational decision support and situationally-sensitive knowledge translation

    ANGLOR: A Composite Machine-Learning Algorithm for Protein Backbone Torsion Angle Prediction

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    We developed a composite machine-learning based algorithm, called ANGLOR, to predict real-value protein backbone torsion angles from amino acid sequences. The input features of ANGLOR include sequence profiles, predicted secondary structure and solvent accessibility. In a large-scale benchmarking test, the mean absolute error (MAE) of the phi/psi prediction is 28°/46°, which is ∼10% lower than that generated by software in literature. The prediction is statistically different from a random predictor (or a purely secondary-structure-based predictor) with p-value <1.0×10−300 (or <1.0×10−148) by Wilcoxon signed rank test. For some residues (ILE, LEU, PRO and VAL) and especially the residues in helix and buried regions, the MAE of phi angles is much smaller (10–20°) than that in other environments. Thus, although the average accuracy of the ANGLOR prediction is still low, the portion of the accurately predicted dihedral angles may be useful in assisting protein fold recognition and ab initio 3D structure modeling

    Statistical learning of peptide retention behavior in chromatographic separations: a new kernel-based approach for computational proteomics

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    <p>Abstract</p> <p>Background</p> <p>High-throughput peptide and protein identification technologies have benefited tremendously from strategies based on tandem mass spectrometry (MS/MS) in combination with database searching algorithms. A major problem with existing methods lies within the significant number of false positive and false negative annotations. So far, standard algorithms for protein identification do not use the information gained from separation processes usually involved in peptide analysis, such as retention time information, which are readily available from chromatographic separation of the sample. Identification can thus be improved by comparing measured retention times to predicted retention times. Current prediction models are derived from a set of measured test analytes but they usually require large amounts of training data.</p> <p>Results</p> <p>We introduce a new kernel function which can be applied in combination with support vector machines to a wide range of computational proteomics problems. We show the performance of this new approach by applying it to the prediction of peptide adsorption/elution behavior in strong anion-exchange solid-phase extraction (SAX-SPE) and ion-pair reversed-phase high-performance liquid chromatography (IP-RP-HPLC). Furthermore, the predicted retention times are used to improve spectrum identifications by a <it>p</it>-value-based filtering approach. The approach was tested on a number of different datasets and shows excellent performance while requiring only very small training sets (about 40 peptides instead of thousands). Using the retention time predictor in our retention time filter improves the fraction of correctly identified peptide mass spectra significantly.</p> <p>Conclusion</p> <p>The proposed kernel function is well-suited for the prediction of chromatographic separation in computational proteomics and requires only a limited amount of training data. The performance of this new method is demonstrated by applying it to peptide retention time prediction in IP-RP-HPLC and prediction of peptide sample fractionation in SAX-SPE. Finally, we incorporate the predicted chromatographic behavior in a <it>p</it>-value based filter to improve peptide identifications based on liquid chromatography-tandem mass spectrometry.</p

    Probucol Suppresses Enterocytic Accumulation of Amyloid-β Induced by Saturated Fat and Cholesterol Feeding

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    Amyloid-β (Aβ) is secreted from lipogenic organs such as intestine and liver as an apolipoprotein of nascent triacylglycerol rich lipoproteins. Chronically elevated plasma Aβ may compromise cerebrovascular integrity and exacerbate amyloidosis—a hallmark feature of Alzheimer’s disease (AD). Probucol is a hypocholesterolemic agent that reduces amyloid burden in transgenic amyloid mice, but the mechanisms for this effect are presently unclear. In this study, the effect of Probucol on intestinal lipoprotein-Aβ homeostasis was explored. Wild-type mice were fed a control low-fat diet and enterocytic Aβ was stimulated by high-fat (HF) diet enriched in 10% (w/w) saturated fat and 1% (w/w) cholesterol for the duration of 1 month. Mice treated with Probucol had the drug incorporated into the chow at 1% (w/w). Quantitative immunofluorescence was utilised to determine intestinal apolipoprotein B (apo B) and Aβ abundance. We found apo B in both the perinuclear region of the enterocytes and the lacteals in all groups. However, HF feeding and Probucol treatment increased secretion of apo B into the lacteals without any change in net villi abundance. On the other hand, HF-induced enterocytic perinuclear Aβ was significantly attenuated by Probucol. No significant changes in Aβ were observed within the lacteals. The findings of this study support the notion that Probucol suppresses dietary fat induced stimulation of Aβ biosynthesis and attenuate availability of apo B lipoprotein-Aβ for secretion

    A novel formulation technology for baculoviruses protects biopesticide from degradation by ultraviolet radiation

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    Biopesticides are biological pest control agents that are viewed as safer alternatives to the synthetic chemicals that dominate the global insecticide market. A major constraint on the wider adoption of biopesticides is their susceptibility to the ultraviolet (UV: 290–400 nm) radiation in sunlight, which limits their persistence and efficacy. Here, we describe a novel formulation technology for biopesticides in which the active ingredient (baculovirus) is micro-encapsulated in an ENTOSTAT wax combined with a UV absorbant (titanium dioxide, TiO2). Importantly, this capsule protects the sensitive viral DNA from degrading in sunlight, but dissolves in the alkaline insect gut to release the virus, which then infects and kills the pest. We show, using simulated sunlight, in both laboratory bioassays and trials on cabbage and tomato plants, that this can extend the efficacy of the biopesticide well beyond the few hours of existing virus formulations, potentially increasing the spray interval and/or reducing the need for high application rates. The new formulation has a shelf-life at 30 °C of at least 6 months, which is comparable to standard commercial biopesticides and has no phytotoxic effect on the host plants. Taken together, these findings suggest that the new formulation technology could reduce the costs and increase the efficacy of baculovirus biopesticides, with the potential to make them commercially competitive alternatives to synthetic chemicals

    Predicting Individuals' Learning Success from Patterns of Pre-Learning MRI Activity

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    Performance in most complex cognitive and psychomotor tasks improves with training, yet the extent of improvement varies among individuals. Is it possible to forecast the benefit that a person might reap from training? Several behavioral measures have been used to predict individual differences in task improvement, but their predictive power is limited. Here we show that individual differences in patterns of time-averaged T2*-weighted MRI images in the dorsal striatum recorded at the initial stage of training predict subsequent learning success in a complex video game with high accuracy. These predictions explained more than half of the variance in learning success among individuals, suggesting that individual differences in neuroanatomy or persistent physiology predict whether and to what extent people will benefit from training in a complex task. Surprisingly, predictions from white matter were highly accurate, while voxels in the gray matter of the dorsal striatum did not contain any information about future training success. Prediction accuracy was higher in the anterior than the posterior half of the dorsal striatum. The link between trainability and the time-averaged T2*-weighted signal in the dorsal striatum reaffirms the role of this part of the basal ganglia in learning and executive functions, such as task-switching and task coordination processes. The ability to predict who will benefit from training by using neuroimaging data collected in the early training phase may have far-reaching implications for the assessment of candidates for specific training programs as well as the study of populations that show deficiencies in learning new skills

    Pembauran Budaya di Desa Rantau Sakti Kecamatan Tambusai Utara Kabupaten Rokan Hulu

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    This study is to research how the intercourse of culture that existed in the Rantau Sakti village Tambusai Utara District and Rokan Hulu Regent intertribal nasions of Java, Medan Java, Batak, Minang, and Melayu. Theres a launching factors and hindrance factors too in culture intercourse. The data tekhnic collection with the koesioner, interview, and documentation. And the analisys of data is descriptive where the data presented in the form of a diagrams, percentages, pictures, and explanations. The research results show that The lives of the multicultural that could lead to the occurrence of intercourse of culture through assimilation, acculturation, and amalgamation. The intercourse of culture through three aspects of it can run well theres happened in Rantau Sakti village on seven principles like language, system of knowledge , a social organization , celebration life and technologi, means of subsistence, religion, and art . There is also intercourse of culture with amalgamation culture that leads to assimilation and acculturation. Its launching factor are the attitude of tolerance and open, in common religion, and the same occasion in the economic field. While the hindrance factor are differences of religion and stereotype (ethnic prejudice). Those two factors each happened to the process of changing culture with assimilation, acculturation, and amalgamation That leads to a positive thing.Keyword: The Culture Intercourse, Inter-ethnic

    Toward a model-based predictive controller design in brain-computer interfaces

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    A first step in designing a robust and optimal model-based predictive controller (MPC) for brain-computer interface (BCI) applications is presented in this article. An MPC has the potential to achieve improved BCI performance compared to the performance achieved by current ad hoc, nonmodel-based filter applications. The parameters in designing the controller were extracted as model-based features from motor imagery task-related human scalp electroencephalography. Although the parameters can be generated from any model-linear or non-linear, we here adopted a simple autoregressive model that has well-established applications in BCI task discriminations. It was shown that the parameters generated for the controller design can as well be used for motor imagery task discriminations with performance (with 8-23% task discrimination errors) comparable to the discrimination performance of the commonly used features such as frequency specific band powers and the AR model parameters directly used. An optimal MPC has significant implications for high performance BCI applications.Grants K25NS061001 (MK) and K02MH01493 (SJS) from the National Institute of Neurological Disorders And Stroke (NINDS) and the National Institute of Mental Health (NIMH), the Portuguese Foundation for Science and Technology (FCT) Grant SFRH/BD/21529/2005 (NSD), the Pennsylvania Department of Community and Economic Development Keystone Innovation Zone Program Fund (SJS), and the Pennsylvania Department of Health using Tobacco Settlement Fund (SJS)

    Ethical considerations in prehospital ambulance based research : qualitative interview study of expert informants

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    Abstract: Background: Prehospital ambulance based research has unique ethical considerations due to urgency, time limitations and the locations involved. We sought to explore these issues through interviews with experts in this research field. Methods: We undertook semi-structured interviews with expert informants, primarily based in the UK, seeking their views and experiences of ethics in ambulance based clinical research. Participants were questioned regarding their experiences of ambulance based research, their opinions on current regulations and guidelines, and views about their general ethical considerations. Participants were chosen because they were actively involved in, or in their expert capacity (e.g. law) expressed an interest in, ambulance based research. Results: Fourteen participants were interviewed including principal investigators, researchers, ethicists and medical lawyers. Five major themes were identified: Capacity, Consent, Clinical Considerations, Consultation and Regulation. Questions regarding consent and capacity were foremost in the discussions as all participants highlighted these as areas for concern. The challenges and use of multiple consent models reflected the complexity of research in this environment. The clinical theme referred to the role of paramedics in research and how research involving ambulance services is increasingly informing improvements to patient care and outcomes and reducing the burden on hospital services. Most felt that, although current regulations were fit for purpose, more specific guidance on implementing these in the ambulance setting would be beneficial. This related closely to the theme of consultation, which examined the key role of ethics committees and other regulatory bodies, as well as public engagement. Conclusions: By interviewing experts in research or ethics in this setting we were able to identify key concerns and highlight areas for future development such as improved guidance
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