370 research outputs found

    Twitter journal clubs and continuing professional development: An analysis of a #MedRadJClub tweet chat

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    Introduction Online Twitter journal clubs are a recent and popular innovation with the potential to increase research awareness and inform practice. The medical radiation sciences' MedRadJournalClub (MJRC) is a Twitter-based event that attracts a global group of participants at the monthly chats. An analysis of a recent MedRadJournalClub discussion evaluated the perceived benefits and limitations of medical radiation practitioners participating in an online journal club. Methods The February 2017 chat used for analysis was based on the Journal of Medical Imaging and Radiation Sciences article by Currie et al. “Twitter Journal Club in Medical Radiation Science” that examines the educational theory behind learning and evidencing professional development through MRJC and social media. The data consisted of chat tweets which were collated using the Twitter advanced search function using the #medradjclub. An initial reviewed was performed to exclude irrelevant content. A second review was then undertaken to categorize the main theme of the tweet. The data were then subjected to thematic analysis which yielded seven different categories. Results The main benefits included global access due to the online nature of MRJC that has facilitated networking and collaboration. Open access to recently published research was another key benefit. The character limitation of a tweet was the most common constraint, and the dynamic nature of the twitter conversation requires multi-tasking that may be difficult. Conclusion Our analysis indicated that participants use MedRadJournalClub as a source of continuing professional development with some evidence that this is directly informing clinical and educational practice

    Functional analysis identifies damaging CHEK2 missense variants associated with increased cancer risk.

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    Heterozygous carriers of germline loss-of-function variants in the tumor suppressor gene checkpoint kinase 2 (CHEK2) are at an increased risk for developing breast and other cancers. While truncating variants in CHEK2 are known to be pathogenic, the interpretation of missense variants of uncertain significance (VUS) is challenging. Consequently, many VUS remain unclassified both functionally and clinically. Here we describe a mouse embryonic stem (mES) cell-based system to quantitatively determine the functional impact of 50 missense VUS in human CHEK2. By assessing the activity of human CHK2 to phosphorylate one of its main targets, Kap1, in Chek2 knockout mES cells, 31 missense VUS in CHEK2 impaired protein function to a similar extent as truncating variants, and 9 CHEK2 missense VUS resulted in intermediate functional defects. Mechanistically, most VUS impaired CHK2 kinase function by causing protein instability or by impairing activation through (auto)phosphorylation. Quantitative results showed that the degree of CHK2 kinase dysfunction correlates with an increased risk for breast cancer. Both damaging CHEK2 variants as a group (OR 2,23; 95% CI 1,62-3,07; pG/p.D162G, was also identified, which co-segregated with familial prostate cancer. Altogether, these functional assays efficiently and reliably identified VUS in CHEK2 that associate with cancer

    Diffuse idiopathic skeletal hyperostosis is associated with incident stroke in patients with increased cardiovascular risk

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    OBJECTIVES: Earlier retrospective studies have suggested a relation between DISH and cardiovascular disease, including myocardial infarction. The present study assessed the association between DISH and incidence of cardiovascular events and mortality in patients with high cardiovascular risk. METHODS: In this prospective cohort study, we included 4624 patients (mean age 58.4 years, 69.6% male) from the Second Manifestations of ARTerial disease cohort. The main end point was major cardiovascular events (MACE: stroke, myocardial infarction and vascular death). Secondary endpoints included all-cause mortality and separate vascular events. Cause-specific proportional hazard models were used to evaluate the risk of DISH on all outcomes, and subdistribution hazard models were used to evaluate the effect of DISH on the cumulative incidence. All models were adjusted for age, sex, body mass index, blood pressure, diabetes, non-HDL cholesterol, packyears, renal function and C-reactive protein. RESULTS: DISH was present in 435 (9.4%) patients. After a median follow-up of 8.7 (IQR 5.0–12.0) years, 864 patients had died and 728 patients developed a MACE event. DISH was associated with an increased cumulative incidence of ischaemic stroke. After adjustment in cause-specific modelling, DISH remained significantly associated with ischaemic stroke (HR 1.55; 95% CI: 1.01, 2.38), but not with MACE (HR 0.99; 95% CI: 0.79, 1.24), myocardial infarction (HR 0.88; 95% CI: 0.59, 1.31), vascular death (HR 0.94; 95% CI: 0.68, 1.27) or all-cause mortality (HR 0.94; 95% CI: 0.77, 1.16). CONCLUSIONS: The presence of DISH is independently associated with an increased incidence and risk for ischaemic stroke, but not with MACE, myocardial infarction, vascular death or all-cause mortality

    U.S. IOOS coastal and ocean modeling testbed : inter-model evaluation of tides, waves, and hurricane surge in the Gulf of Mexico

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    © The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Geophysical Research: Oceans 118 (2013): 5129–5172, doi:10.1002/jgrc.20376.A Gulf of Mexico performance evaluation and comparison of coastal circulation and wave models was executed through harmonic analyses of tidal simulations, hindcasts of Hurricane Ike (2008) and Rita (2005), and a benchmarking study. Three unstructured coastal circulation models (ADCIRC, FVCOM, and SELFE) validated with similar skill on a new common Gulf scale mesh (ULLR) with identical frictional parameterization and forcing for the tidal validation and hurricane hindcasts. Coupled circulation and wave models, SWAN+ADCIRC and WWMII+SELFE, along with FVCOM loosely coupled with SWAN, also validated with similar skill. NOAA's official operational forecast storm surge model (SLOSH) was implemented on local and Gulf scale meshes with the same wind stress and pressure forcing used by the unstructured models for hindcasts of Ike and Rita. SLOSH's local meshes failed to capture regional processes such as Ike's forerunner and the results from the Gulf scale mesh further suggest shortcomings may be due to a combination of poor mesh resolution, missing internal physics such as tides and nonlinear advection, and SLOSH's internal frictional parameterization. In addition, these models were benchmarked to assess and compare execution speed and scalability for a prototypical operational simulation. It was apparent that a higher number of computational cores are needed for the unstructured models to meet similar operational implementation requirements to SLOSH, and that some of them could benefit from improved parallelization and faster execution speed.This project was supported by NOAA via the U.S. IOOS Office (award: NA10NOS0120063 and NA11NOS0120141

    Cancer treatment induced metabolic syndrome:Improving outcome with lifestyle

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    Increasing numbers of long-term cancer survivors face important treatment related adverse effects. Cancer treatment induced metabolic syndrome (CTIMetS) is an especially prevalent and harmful condition. The aetiology of CTIMetS likely differs from metabolic syndrome in the general population, but effective treatment and prevention methods are probably similar. In this review, we summarize the potential mechanisms leading to the development of CTIMetS after various types of cancer treatment. Furthermore, we propose a safe and accessible method to treat or prevent CTIMetS through lifestyle change. In particular, we suggest that a lifestyle intervention and optimization of energy balance can prevent or mitigate the development of CTIMetS, which may contribute to optimal survivorship care. (C) 2016 Elsevier Ireland Ltd. All rights reserved

    Tune in to your emotions: a robust personalized affective music player

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    The emotional power of music is exploited in a personalized affective music player (AMP) that selects music for mood enhancement. A biosignal approach is used to measure listeners’ personal emotional reactions to their own music as input for affective user models. Regression and kernel density estimation are applied to model the physiological changes the music elicits. Using these models, personalized music selections based on an affective goal state can be made. The AMP was validated in real-world trials over the course of several weeks. Results show that our models can cope with noisy situations and handle large inter-individual differences in the music domain. The AMP augments music listening where its techniques enable automated affect guidance. Our approach provides valuable insights for affective computing and user modeling, for which the AMP is a suitable carrier application

    Physically-based Assessment of Hurricane Surge Threat under Climate Change

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    Storm surges are responsible for much of the damage and loss of life associated with landfalling hurricanes. Understanding how global warming will affect hurricane surges thus holds great interest. As general circulation models (GCMs) cannot simulate hurricane surges directly, we couple a GCM-driven hurricane model with hydrodynamic models to simulate large numbers of synthetic surge events under projected climates and assess surge threat, as an example, for New York City (NYC). Struck by many intense hurricanes in recorded history and prehistory, NYC is highly vulnerable to storm surges. We show that the change of storm climatology will probably increase the surge risk for NYC; results based on two GCMs show the distribution of surge levels shifting to higher values by a magnitude comparable to the projected sea-level rise (SLR). The combined effects of storm climatology change and a 1 m SLR may cause the present NYC 100-yr surge flooding to occur every 3–20 yr and the present 500-yr flooding to occur every 25–240 yr by the end of the century.United States. National Oceanic and Atmospheric Administration (Postdoctoral Fellowship Program)National Science Foundation (U.S.

    Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

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    In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

    Report from the EPAA workshop: In vitro ADME in safety testing used by EPAA industry sectors

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    AbstractThere are now numerous in vitro and in silico ADME alternatives to in vivo assays but how do different industries incorporate them into their decision tree approaches for risk assessment, bearing in mind that the chemicals tested are intended for widely varying purposes? The extent of the use of animal tests is mainly driven by regulations or by the lack of a suitable in vitro model. Therefore, what considerations are needed for alternative models and how can they be improved so that they can be used as part of the risk assessment process? To address these issues, the European Partnership for Alternative Approaches to Animal Testing (EPAA) working group on prioritisation, promotion and implementation of the 3Rs research held a workshop in November, 2008 in Duesseldorf, Germany. Participants included different industry sectors such as pharmaceuticals, cosmetics, industrial- and agro-chemicals. This report describes the outcome of the discussions and recommendations (a) to reduce the number of animals used for determining the ADME properties of chemicals and (b) for considerations and actions regarding in vitro and in silico assays. These included: standardisation and promotion of in vitro assays so that they may become accepted by regulators; increased availability of industry in vivo kinetic data for a central database to increase the power of in silico predictions; expansion of the applicability domains of in vitro and in silico tools (which are not necessarily more applicable or even exclusive to one particular sector) and continued collaborations between regulators, academia and industry. A recommended immediate course of action was to establish an expert panel of users, developers and regulators to define the testing scope of models for different chemical classes. It was agreed by all participants that improvement and harmonization of alternative approaches is needed for all sectors and this will most effectively be achieved by stakeholders from different sectors sharing data
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