1,318 research outputs found

    Decision Analysis for the Evaluation of Risk in Nuclear Waste Management

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    The implementation of a nuclear waste management technology raises several issues concerning the regulation of social risk. The most basic of those issues are how to regulate a technology when the uncertainties in social consequences are important, and how to incorporate the relevant social values in the regulations. This paper presents a decision analytic approach to resolving these issues, based on the development of radiological risk evaluation indices. While it is essentially a case study, describing work carried out for the U.S. Nuclear Regulatory Commission, this case is used to discuss the more general issues involved. We begin by discussing the need for risk evaluation to provide a clear and defensible basis for regulating technologies involving social risk. We then present an overview of the problem of evaluating the risk of nuclear waste management, and an overview of our approach. That is followed by a development of risk evaluation indices for the regulation of nuclear waste management. The indices developed are expected utilities, based on preferences elicited from groups of people. The use of the indices developed is illustrated in a hypothetical example. Finally, components of the analysis requiring further development are identified and discussed, and the usefulness of the methodology evaluated

    PMS70 Tumor Necrosis Factor (TNF)-Blocker Dose Escalation among Patients with Rheumatoid Arthritis (RA) in a Large Managed Care Population in the United States

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    Do theories of change enable innovation platforms?

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    Theories of change (ToCs) are increasingly used to articulate pathways for interventions and to support learning. This responds to the recognition of the complexity of agricultural development. Through two examples, this paper examines how ToCs have enabled practitioners to navigate towards impact in settings characterized by a multiplicity of views from different actors on issues of joint concern. The cases discuss how the intervention programs test the ToCs, as well as organize and reflect on feedback. The cases reveal that one cannot predict the route to impact, but one can compose plausible story lines explicating the assumptions. Developing and using ToCs takes time and requires a deliberate effort to monitor actions and changes. Connecting practitioners with researchers makes it possible to use more intermediate theorisations tailored to situated and specific impact pathways. However, the dynamics captured by ToCs may contrast with the donors’ demands for accountability and consistent reliance on a rigid log-frame approach to determine project activities and outputs. Therefore, it is relevant to make explicit choices about how to relate ToCs to M&E efforts

    Model thrombi formed under flow reveal the role of factor XIII-mediated cross-linking in resistance to fibrinolysis

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    Background: Activated factor XIII (FXIIIa), a transglutaminase, introduces fibrin-fibrin and fibrin-inhibitor cross-links, resulting in more mechanically stable clots. The impact of cross-linking on resistance to fibrinolysis has proved challenging to evaluate quantitatively. Methods: We used a whole blood model thrombus system to characterize the role of cross-linking in resistance to fibrinolytic degradation. Model thrombi, which mimic arterial thrombi formed in vivo, were prepared with incorporated fluorescently labeled fibrinogen, in order to allow quantification of fibrinolysis as released fluorescence units per minute. Results: A site-specific inhibitor of transglutaminases, added to blood from normal donors, yielded model thrombi that lysed more easily, either spontaneously or by plasminogen activators. This was observed both in the cell/platelet-rich head and fibrin-rich tail. Model thrombi from an FXIII-deficient patient lysed more quickly than normal thrombi; replacement therapy with FXIII concentrate normalized lysis. In vitro addition of purified FXIII to the patient's preprophylaxis blood, but not to normal control blood, resulted in more stable thrombi, indicating no further efficacy of supraphysiologic FXIII. However, addition of tissue transglutaminase, which is synthesized by endothelial cells, generated thrombi that were more resistant to fibrinolysis; this may stabilize mural thrombi in vivo. Conclusions: Model thrombi formed under flow, even those prepared as plasma 'thrombi', reveal the effect of FXIII on fibrinolysis. Although very low levels of FXIII are known to produce mechanical clot stability, and to achieve ?-dimerization, they appear to be suboptimal in conferring full resistance to fibrinolysis

    CO1 COMPARATIVE EFFECTIVENESS ANALYSIS OF TNF BLOCKERS IN RHEUMATOID ARTHRITIS (RA) PATIENTS IN A REAL-WORLD SETTING

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    Eye-movements reveal attention to social information in autism spectrum disorder

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    Autism spectrum disorder (ASD) is a neurodevelopmental condition in which children show reduced attention to social aspects of the environment. However in adults with ASD, evidence for social attentional deficits is equivocal. One problem is that many paradigms present social information in an unrealistic, isolated way. This study presented adults and adolescents, with and without ASD, with a complex social scene alongside another, non-social scene, and measured eye-movements during a 3-s viewing period. Analyses first identified viewing time to different regions and then investigated some more complex issues. These were: the location of the very first fixation in a trial (indicating attentional priority); the effect of a task instruction on scan paths; the extent to which gaze-following was evident; and the degree to which participants’ scan paths were influenced by the low-level properties of a scene. Results indicate a superficially normal attentional preference for social information in adults with ASD. However, more sensitive measures show that ASD does entail social attention problems across the lifespan, supporting accounts of the disorder which emphasise lifelong neurodevelopmental atypicalities. These subtle abnormalities may be sufficient to produce serious difficulties in real-life scenarios

    Direct visualisation of collateral ventilation in COPD with hyperpolarised gas MRI

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    Abstract Background Collateral ventilation has been proposed as a mechanism of compensation of respiratory function in obstructive lung diseases but observations of it in vivo are limited. The assessment of collateral ventilation with an imaging technique might help to gain insight into lung physiology and assist the planning of new bronchoscopic techniques for treating emphysema. Objective To obtain images of delayed ventilation that might be related to collateral ventilation over the period of a single breath-hold in patients with chronic obstructive pulmonary disease (COPD). Methods Time-resolved breath-hold hyperpolarised 3He MRI was used to obtain images of the progressive influx of polarised gas into initially non-ventilated defects. Results A time-series of images showed that 3He moves into lung regions which were initially non-ventilated. Ventilation defects with delayed filling were observed in 8 of the 10 patients scanned. Conclusions A method for direct imaging of delayed ventilation within a single breath-hold has been demonstrated in patients with COPD. Images of what is believed to be collateral ventilation and slow filling of peripheral airspaces due to increased flow resistance are presented. The technique provides 3D whole-lung coverage with sensitivity to regional information, and is non-invasive and non-ionising
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