3,921 research outputs found

    Improving Proficiency in Central Venous Catheter Insertion: Standardized Simulation Based Training for Internal Medicine House Staff

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    Objectives: The objectives of this study are to assess residents\u27 pre-workshop ability and comfort with CVC placement, undergo a standardized online didactic and hands-on clinical training simulation workshop, and subsequently undergo a proficiency test using simulation models to assess competency. The goal of a standardized training module is to create a universal approach to CVC placement in our institution and improve comfort and technical ability of house staff. We hypothesize that this will reduce complications and improve patient care and safety.https://jdc.jefferson.edu/patientsafetyposters/1063/thumbnail.jp

    VEZF1 elements mediate protection from DNA methylation

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    There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm β-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin stat

    On the infrared behaviour of 3d Chern-Simons theories in N=2 superspace

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    We discuss the problem of infrared divergences in the N=2 superspace approach to classically marginal three-dimensional Chern-Simons-matter theories. Considering the specific case of ABJM theory, we describe the origin of such divergences and offer a prescription to eliminate them by introducing non-trivial gauge-fixing terms in the action. We also comment on the extension of our procedure to higher loop order and to general three-dimensional Chern-Simons-matter models.Comment: 26 pages, 6 figures, JHEP3; v2: minor corrections and references added; v3: introduction expanded, presentation of section 3.3.1 improved, references added, version to appear in JHE

    Regulation of Ventral Tegmental Area Dopamine Neuron Activity by Feeding-related Hypothalamic Neuropeptides

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    The prevalence of obesity has doubled worldwide since the 1980s, and having a high body mass index contributes to more deaths worldwide than being underweight. Over the past 20 years, consumption of calorie-dense foods has increased, and this is considered one of the major causes of the rapid rise in obesity. Thus, understanding the neural control of food intake is important for the development of new and effective treatments of obesity. Two important brain regions that regulate food intake are the hypothalamus and the mesocorticolimbic dopamine system. The hypothalamus is essential for the homeostatic control of feeding and body weight, while the mesocorticolimbic dopamine system, also known as the reward system, is the primary circuit for reward and motivated behavior. The reward system also regulates food intake and food reward, and there is increasing evidence that hypothalamic feeding-related neuropeptides alter dopamine neuron activity to affect feeding. Nevertheless, how these neuropeptides interact with the reward system to regulate feeding is not fully understood. For example, centrally delivered neurotensin and neuropeptide-Y (NPY) increase dopamine release in the nucleus accumbens, but cause opposite effects on food reward. In addition, injection of the hypothalamic neuropeptides neurotensin, NPY, or alpha-melanocyte-stimulating hormone (a-MSH) into the ventral tegmental area (VTA), where reward-related dopamine neurons are located, alters multiple aspects of feeding, but how these neuropeptides interact with the reward system to alter feeding at both the circuit and cellular levels is not fully understood. In these studies, I have used whole cell patch-clamp electrophysiology in acute brain slices from mice to examine how neurotensin, a-MSH, and NPY affect VTA dopamine neuron activity. I have demonstrated that these neuropeptides use multiple mechanisms to alter VTA dopamine neuron activity, including both pre- and post-synaptic mechanisms. Neurotensin and a-MSH increased dopamine neuron activity, while NPY had both excitatory and inhibitory effects on dopamine neuron activity. Overall, these studies provide an important advancement in our understanding of the different mechanisms utilized by hypothalamic neuropeptides to alter VTA dopamine neuron activity and how hypothalamic neuropeptides interact with the mesocorticolimbic dopamine system to control food intake and food reward

    Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands

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    "© 2015 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited"Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18 -25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation)

    Optimally combining dynamical decoupling and quantum error correction

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    We show how dynamical decoupling (DD) and quantum error correction (QEC) can be optimally combined in the setting of fault tolerant quantum computing. To this end we identify the optimal generator set of DD sequences designed to protect quantum information encoded into stabilizer subspace or subsystem codes. This generator set, comprising the stabilizers and logical operators of the code, minimizes a natural cost function associated with the length of DD sequences. We prove that with the optimal generator set the restrictive local-bath assumption used in earlier work on hybrid DD-QEC schemes, can be significantly relaxed, thus bringing hybrid DD-QEC schemes, and their potentially considerable advantages, closer to realization.Comment: 6 pages, 1 figur

    Toward evidence-based teaching: evaluating the effectiveness of two teaching strategies in an associate degree nursing program

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    The need for evidence based teaching has become an important ideology for nurse educators who are frequently encouraged to expand their teaching strategies based on recent advances in technology and student learning styles. Traditional lecture is often preferred by students, yet the literature encourages case study methodology for the development of critical thinking. A pilot study was conducted comparing learning outcomes using two different teaching strategies: lecture and case study instruction. Recommendations for using case study as a teaching methodology are offered

    Structure of the hDmc1-ssDNA filament reveals the principles of its architecture

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    In eukaryotes, meiotic recombination is a major source of genetic diversity, but its defects in humans lead to abnormalities such as Down's, Klinefelter's and other syndromes. Human Dmc1 (hDmc1), a RecA/Rad51 homologue, is a recombinase that plays a crucial role in faithful chromosome segregation during meiosis. The initial step of homologous recombination occurs when hDmc1 forms a filament on single-stranded (ss) DNA. However the structure of this presynaptic complex filament for hDmc1 remains unknown. To compare hDmc1-ssDNA complexes to those known for the RecA/Rad51 family we have obtained electron microscopy (EM) structures of hDmc1-ssDNA nucleoprotein filaments using single particle approach. The EM maps were analysed by docking crystal structures of Dmc1, Rad51, RadA, RecA and DNA. To fully characterise hDmc1-DNA complexes we have analysed their organisation in the presence of Ca2+, Mg2+, ATP, AMP-PNP, ssDNA and dsDNA. The 3D EM structures of the hDmc1-ssDNA filaments allowed us to elucidate the principles of their internal architecture. Similar to the RecA/Rad51 family, hDmc1 forms helical filaments on ssDNA in two states: extended (active) and compressed (inactive). However, in contrast to the RecA/Rad51 family, and the recently reported structure of hDmc1-double stranded (ds) DNA nucleoprotein filaments, the extended (active) state of the hDmc1 filament formed on ssDNA has nine protomers per helical turn, instead of the conventional six, resulting in one protomer covering two nucleotides instead of three. The control reconstruction of the hDmc1-dsDNA filament revealed 6.4 protein subunits per helical turn indicating that the filament organisation varies depending on the DNA templates. Our structural analysis has also revealed that the N-terminal domain of hDmc1 accomplishes its important role in complex formation through domain swapping between adjacent protomers, thus providing a mechanistic basis for coordinated action of hDmc1 protomers during meiotic recombination

    Fast flowing populations are not well mixed

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    In evolutionary dynamics, well-mixed populations are almost always associated with all-to-all interactions; mathematical models are based on complete graphs. In most cases, these models do not predict fixation probabilities in groups of individuals mixed by flows. We propose an analytical description in the fast-flow limit. This approach is valid for processes with global and local selection, and accurately predicts the suppression of selection as competition becomes more local. It provides a modelling tool for biological or social systems with individuals in motion.Comment: 19 pages, 8 figure
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