1,475 research outputs found

    An NIH intramural percubator as a model of academic-industry partnerships: from the beginning of life through the valley of death

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    In 2009 the NIH publicly announced five strategic goals for the institutes that included the critical need to translate research discoveries into public benefit at an accelerated pace, with a commitment to find novel ways to engage academic investigators in the process. The emphasis on moving scientific advancements from the laboratory to the clinic is an opportune time to discuss how the NIH intramural program in Bethesda, the largest biomedical research center in the world, can participate in this endeavor. Proposed here for consideration is a percolator-incubator program, a 'percubator' designed to enable NIH intramural investigators to develop new medical interventions as quickly and efficiently as possible

    Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial

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    Date of acceptance: 01/07/2015 © 2015 Witham et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements UK NIHR HTA grant 10/71/01. We acknowledge the financial support of NHS Research Scotland in conducting this trial.Peer reviewedPublisher PD

    Epidemiology and reporting characteristics of preclinical systematic reviews

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    In an effort to better utilize published evidence obtained from animal experiments, systematic reviews of preclinical studies are increasingly more common-along with the methods and tools to appraise them (e.g., SYstematic Review Center for Laboratory animal Experimentation [SYRCLE's] risk of bias tool). We performed a cross-sectional study of a sample of recent preclinical systematic reviews (2015-2018) and examined a range of epidemiological characteristics and used a 46-item checklist to assess reporting details. We identified 442 reviews published across 43 countries in 23 different disease domains that used 26 animal species. Reporting of key details to ensure transparency and reproducibility was inconsistent across reviews and within article sections. Items were most completely reported in the title, introduction, and results sections of the reviews, while least reported in the methods and discussion sections. Less than half of reviews reported that a risk of bias assessment for internal and external validity was undertaken, and none reported methods for evaluating construct validity. Our results demonstrate that a considerable number of preclinical systematic reviews investigating diverse topics have been conducted; however, their quality of reporting is inconsistent. Our study provides the justification and evidence to inform the development of guidelines for conducting and reporting preclinical systematic reviews

    Alcohol affects neuronal substrates of response inhibition but not of perceptual processing of stimuli signalling a stop response

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    Alcohol impairs inhibitory control, including the ability to terminate an initiated action. While there is increasing knowledge about neural mechanisms involved in response inhibition, the level at which alcohol impairs such mechanisms remains poorly understood. Thirty-nine healthy social drinkers received either 0.4g/kg or 0.8g/kg of alcohol, or placebo, and performed two variants of a Visual Stop-signal task during acquisition of functional magnetic resonance imaging (fMRI) data. The two task variants differed only in their instructions: in the classic variant (VSST), participants inhibited their response to a “Go-stimulus” when it was followed by a “Stop-stimulus”. In the control variant (VSST_C), participants responded to the “Go-stimulus” even if it was followed by a “Stop-stimulus”. Comparison of successful Stop-trials (Sstop)>Go, and unsuccessful Stop-trials (Ustop)>Sstop between the three beverage groups enabled the identification of alcohol effects on functional neural circuits supporting inhibitory behaviour and error processing. Alcohol impaired inhibitory control as measured by the Stop-signal reaction time, but did not affect other aspects of VSST performance, nor performance on the VSST_C. The low alcohol dose evoked changes in neural activity within prefrontal, temporal, occipital and motor cortices. The high alcohol dose evoked changes in activity in areas affected by the low dose but importantly induced changes in activity within subcortical centres including the globus pallidus and thalamus. Alcohol did not affect neural correlates of perceptual processing of infrequent cues, as revealed by conjunction analyses of VSST and VSST_C tasks. Alcohol ingestion compromises the inhibitory control of action by modulating cortical regions supporting attentional, sensorimotor and action-planning processes. At higher doses the impact of alcohol also extends to affect subcortical nodes of fronto-basal ganglia- thalamo-cortical motor circuits. In contrast, alcohol appears to have little impact on the early visual processing of infrequent perceptual cues. These observations clarify clinically-important effects of alcohol on behaviour

    AdS_3/LCFT_2 - Correlators in Cosmological Topologically Massive Gravity

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    For cosmological topologically massive gravity at the chiral point we calculate momentum space 2- and 3-point correlators of operators in the postulated dual CFT on the cylinder. These operators are sourced by the bulk and boundary gravitons. Our correlators are fully consistent with the proposal that cosmological topologically massive gravity at the chiral point is dual to a logarithmic CFT. In the process we give a complete classification of normalizable and non-normalizeable left, right and logarithmic solutions to the linearized equations of motion in global AdS_3.Comment: 39 pages + appendices, 1 eps figure, v2: minor changes in text in 4.1.2, corrected typo in (2.31

    Identification of storage conditions stabilizing extracellular vesicles pre

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    Extracellular vesicles (EVs) play a key role in many physiological and pathophysiological processes and hold great potential for therapeutic and diagnostic use. Despite significant advances within the last decade, the key issue of EV storage stability remains unresolved and under investigated. Here, we aimed to identify storage conditions stabilizing EVs and comprehensively compared the impact of various storage buffer formulations at different temperatures on EVs derived from different cellular sources for up to 2 years. EV features including concentration, diameter, surface protein profile and nucleic acid contents were assessed by complementary methods, and engineered EVs containing fluorophores or functionalized surface proteins were utilized to compare cellular uptake and ligand binding. We show that storing EVs in PBS over time leads to drastically reduced recovery particularly for pure EV samples at all temperatures tested, starting already within days. We further report that using PBS as diluent was found to result in severely reduced EV recovery rates already within minutes. Several of the tested new buffer conditions largely prevented the observed effects, the lead candidate being PBS supplemented with human albumin and trehalose (PBS-HAT). We report that PBS-HAT buffer facilitates clearly improved short-term and long-term EV preservation for samples stored at -80°C, stability throughout several freeze-thaw cycles, and drastically improved EV recovery when using a diluent for EV samples for downstream applications

    Oppilaitten eettinen toimijuus videotutkimuksessa

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    The rapid development of various recording technologies in recent years has created appealing opportunities for researchers to document and study science, technology, engineering, and mathematics (STEM) learning in ways which previously were either impossible, high-priced, or impractical. The potential access that low-cost and ever-smaller recorders provide us has been wisely tempered with cautions that researchers critically reflect on whether the benefits of the research outweigh the invasion of participants’ privacy, especially in research with children. These cautions rightfully place the burden of ethical deliberation on the researcher. However, by so doing they also direct attention away from the ethical work done by study participants and overshadow their agency in relation to the research. In effect, the cautions join and reinforce dominant narratives of participant, especially children’s, vulnerability in research and the researcher as the main ethical actor during the research process. This study seeks to balance such narratives by drawing attention to how children demonstrate their awareness of the audience of nearby recorders to each other and, through such actions, also create spaces for private, out-of-view interaction they do not wish to be recorded. With demonstrative vignettes from a yearlong ethnographic study of children’s learning in an alternative STEM learning infrastructure, the study argues that such moments highlight children’s ethical agency in research.The rapid development of various recording technologies in recent years has created appealing opportunities for researchers to document and study science, technology, engineering, and mathematics (STEM) learning in ways which previously were either impossible, high-priced, or impractical. The potential access that low-cost and ever-smaller recorders provide us has been wisely tempered with cautions that researchers critically reflect on whether the benefits of the research outweigh the invasion of participants’ privacy, especially in research with children. These cautions rightfully place the burden of ethical deliberation on the researcher. However, by so doing they also direct attention away from the ethical work done by study participants and overshadow their agency in relation to the research. In effect, the cautions join and reinforce dominant narratives of participants’, especially children’s, vulnerability in research and the researcher as the main ethical actor during the research process. This study seeks to balance such narratives by drawing attention to how children demonstrate their awareness of the audience of nearby recorders to each other and, through such actions, also create spaces for private, out-of-view interaction they do not wish to be recorded. With demonstrative vignettes from a yearlong ethnographic study of children’s learning in an alternative STEM learning infrastructure, the study argues that such moments highlight children’s ethical agency in research.Peer reviewe

    Childbearing intentions in a low fertility context: the case of Romania

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    This paper applies the Theory of Planned Behaviour (TPB) to find out the predictors of fertility intentions in Romania, a low-fertility country. We analyse how attitudes, subjective norms and perceived behavioural control relate to the intention to have a child among childless individuals and one-child parents. Principal axis factor analysis confirms which items proposed by the Generation and Gender Survey (GGS 2005) act as valid and reliable measures of the suggested theoretical socio-psychological factors. Four parity-specific logistic regression models are applied to evaluate the relationship between the socio-psychological factors and childbearing intentions. Social pressure emerges as the most important aspect in fertility decision-making among childless individuals and one-child parents, and positive attitudes towards childbearing are a strong component in planning for a child. This paper also underlines the importance of the region-specific factors when studying childbearing intentions: planning for the second child significantly differs among the development regions, representing the cultural and socio-economic divisions of the Romanian territory
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