353 research outputs found

    Aortic Coarctation Following Aortic Valve Replacement: Problem Solving with Multimodality Cardiac Imaging

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    Contributions of Muscles and External Forces to Medial Knee Load Reduction Due to Osteoarthritis Braces

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    Background Braces for medial knee osteoarthritis can reduce medial joint loads through a combination of three mechanisms: application of an external brace abduction moment, alteration of gait dynamics, and reduced activation of antagonistic muscles. Although the effect of knee bracing has been reported independently for each of these parameters, no previous study has quantified their relative contributions to reducing medial knee loads. Methods In this study, we used a detailed musculoskeletal model to investigate immediate changes in medial and lateral loads caused by two different knee braces: OA Assist and OA Adjuster 3 (DJO Global). Seventeen osteoarthritis subjects and eighteen healthy controls performed overground gait trials in unbraced and braced conditions. Results Across all subjects, bracing reduced medial loads by 0.1 to 0.3 times bodyweight (BW), or roughly 10%, and increased lateral loads by 0.03 to 0.2 BW. Changes in gait kinematics due to bracing were subtle, and had little effect on medial and lateral joint loads. The knee adduction moment was unaltered unless the brace moment was included in its computation. Only one muscle, biceps femoris, showed a significant change in EMG with bracing, but this did not contribute to altered peak medial contact loads. Conclusions Knee braces reduced medial tibiofemoral loads primarily by applying a direct, and substantial, abduction moment to each subject's knee. To further enhance brace effectiveness, future brace designs should seek to enhance the magnitude of this unloader moment, and possibly exploit additional kinematic or neuromuscular gait modifications

    Folding Circular Permutants of IL-1β: Route Selection Driven by Functional Frustration

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    Interleukin-1β (IL-1β) is the cytokine crucial to inflammatory and immune response. Two dominant routes are populated in the folding to native structure. These distinct routes are a result of the competition between early packing of the functional loops versus closure of the β-barrel to achieve efficient folding and have been observed both experimentally and computationally. Kinetic experiments on the WT protein established that the dominant route is characterized by early packing of geometrically frustrated functional loops. However, deletion of one of the functional loops, the β-bulge, switches the dominant route to an alternative, yet, as accessible, route, where the termini necessary for barrel closure form first. Here, we explore the effect of circular permutation of the WT sequence on the observed folding landscape with a combination of kinetic and thermodynamic experiments. Our experiments show that while the rate of formation of permutant protein is always slower than that observed for the WT sequence, the region of initial nucleation for all permutants is similar to that observed for the WT protein and occurs within a similar timescale. That is, even permutants with significant sequence rearrangement in which the functional-nucleus is placed at opposing ends of the polypeptide chain, fold by the dominant WT “functional loop-packing route”, despite the entropic cost of having to fold the N- and C- termini early. Taken together, our results indicate that the early packing of the functional loops dominates the folding landscape in active proteins, and, despite the entropic penalty of coalescing the termini early, these proteins will populate an entropically unfavorable route in order to conserve function. More generally, circular permutation can elucidate the influence of local energetic stabilization of functional regions within a protein, where topological complexity creates a mismatch between energetics and topology in active proteins

    Taking Action Together: A YMCA-based protocol to prevent Type-2 Diabetes in high-BMI inner-city African American children

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    <p>Abstract</p> <p>Background</p> <p>Associated with a tripling in obesity since 1970, type 2 diabetes mellitus (T2DM) in children has risen 9-10 fold. There is a critical need of protocols for trials to prevent T2DM in children.</p> <p>Methods/Design</p> <p>This protocol includes the theory, development, evaluation components and lessons learned from a novel YMCA-based T2DM prevention intervention designed specifically for high-BMI African American children from disadvantaged, inner-city neighborhoods of Oakland, California. The intervention was developed on the basis of: review of epidemiological and intervention studies of pediatric T2DM; a conceptual theory (social cognitive); a comprehensive examination of health promotion curricula designed for children; consultation with research, clinical experts and practitioners and; input from community partners. The intervention, <it>Taking Action Together</it>, included culturally sensitive and age-appropriate programming on: healthy eating; increasing physical activity and, improving self esteem.</p> <p>Discussion</p> <p>Evaluations completed to date suggest that <it>Taking Action Together </it>may be an effective intervention, and results warrant an expanded evaluation effort. This protocol could be used in other community settings to reduce the risk of children developing T2DM and related health consequences.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT01039116.</p

    NAFTA Chapter 11 as Supraconstitution

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    More and more legal scholars are turning to constitutional law to make sense of the growth of transnational and international legal orders. They often employ constitutional terminology loosely, in a bewildering variety of ways, with little effort to clarify their analytical frameworks or acknowledge the normative presuppositions embedded in their analysis. The potential of constitutional analysis as an instrument of critique of transnational legal orders is frequently lost in methodological confusion and normative controversy. An effort at clarification is necessary. We propose a functional approach to supraconstitutional analysis that applies across issue areas, accommodates variation in kinds and degrees of supraconstitutionalization, recognizes its simultaneously domestic and transnational character, and reflects its uneven incidence and impacts. We apply this framework to NAFTA to consider whether and how it superimposes a supraconstitutional legal order on member states\u27 domestic constitutional orders. We show that the main thrust of this contemporary supraconstitutional project is to restructure state and international political forms to promote market efficiency and discipline, enable free capital movement, confer privileged rights of citizenship and representation on corporate capital, insulate key aspects of the economy from state interference, and constrain democratic decision-making

    From 'trading zones' to 'buffer zones': Art and metaphor in the communication of psychiatric genetics to publics

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    Psychiatric genetics has a difficult relationship with the public given its unshakeable connection to eugenics. Drawing from a five-year public engagement programme that emerged from an internationally renowned psychiatric genetics centre, we propose the concept of the Buffer Zone to consider how an exchange of viewpoints between groups of people – including psychiatric geneticists and lay publics - who are often uneasy in one another’s company can be facilitated through the use of art and metaphor. The artwork at the exhibitions provided the necessary socio-cultural context for scientific endeavours, whilst also enabled public groups to be part of, and remain in, the conversation. Crucial to stress is that this mitigation was not to protect the science; it was to protect the discussion

    Inductively coupled plasma mass spectrometric detection for multielement flow injection analysis and elemental speciation by reversed-phase liquid chromatography

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    The feasibility of using an inductively coupled plasma mass spectrometer as a muitieiement detector for flow injection analysis (FIA) and ion-pair reversed-phase liquid chromatography was investigated. Sample introduction was by uitrasonk nebulization with aerosol desolvation. Absolute detecton limits for FIA ranged from 0.01 to 0.1 ng for most elements using 10-pL injections. Over 30 elements were surveyed for their response to both anionic and cationic ion pairing reagents. The separation and selective detection of various As and Se species were demonstrated, yielding detection limits near 0.1 ng (as element) for ail six species present. Determination of 15 elements in a single injection with multiple ion monitoring produced shniiar detection limits. Isotope ratios were measured with sufficient precision (better than 2%) and accuracy (about 1 %) on eluting peaks of Cd and Pb to demonstrate that liquid chromatographyhductively coupled plasma mass spectrometry should make speciation studies with stable tracer isotopes feasible
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