926 research outputs found

    What The Oregon Health Study Can Tell Us About Expanding Medicaid

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    The recently enacted Patient Protection and Affordable Care Act includes a major expansion of Medicaid to low-income adults in 2014. This paper describes the Oregon Health Study, a randomized controlled trial that will be able to shed some light on the likely effects of such expansions. In 2008, Oregon randomly drew names from a waiting list for its previously closed public insurance program. Our analysis of enrollment into this program found that people who signed up for the waiting list and enrolled in the Oregon Medicaid program were likely to have worse health than those who did not. However, actual enrollment was fairly low, partly because many applicants did not meet eligibility standards.United States. Dept. of Health and Human Services. Office of the Assistant Secretary for Planning and EvaluationCalifornia HealthCare FoundationJohn D. and Catherine T. MacArthur FoundationNational Institute on AgingRobert Wood Johnson FoundationAlfred P. Sloan FoundationUnited States. Social Security Administratio

    Estimation of colorectal adenoma recurrence with dependent censoring

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    <p>Abstract</p> <p>Background</p> <p>Due to early colonoscopy for some participants, interval-censored observations can be introduced into the data of a colorectal polyp prevention trial. The censoring could be dependent of risk of recurrence if the reasons of having early colonoscopy are associated with recurrence. This can complicate estimation of the recurrence rate.</p> <p>Methods</p> <p>We propose to use midpoint imputation to convert interval-censored data problems to right censored data problems. To adjust for potential dependent censoring, we use information from auxiliary variables to define risk groups to perform the weighted Kaplan-Meier estimation to the midpoint imputed data. The risk groups are defined using two risk scores derived from two working proportional hazards models with the auxiliary variables as the covariates. One is for the recurrence time and the other is for the censoring time. The method described here is explored by simulation and illustrated with an example from a colorectal polyp prevention trial.</p> <p>Results</p> <p>We first show that midpoint imputation under an assumption of independent censoring will produce an unbiased estimate of recurrence rate at the end of the trial, which is often the main interest of a colorectal polyp prevention trial, and then show in simulations that the weighted Kaplan-Meier method using the information from auxiliary variables based on the midpoint imputed data can improve efficiency in a situation with independent censoring and reduce bias in a situation with dependent censoring compared to the conventional methods, while estimating the recurrence rate at the end of the trial.</p> <p>Conclusion</p> <p>The research in this paper uses midpoint imputation to handle interval-censored observations and then uses the information from auxiliary variables to adjust for dependent censoring by incorporating them into the weighted Kaplan-Meier estimation. This approach can handle a situation with multiple auxiliary variables by deriving two risk scores from two working PH models. Although the idea of this approach might appear simple, the results do show that the weighted Kaplan-Meier approach can gain efficiency and reduce bias due to dependent censoring.</p

    Estimation of Recurrence of Colorectal Adenomas with Dependent Censoring Using Weighted Logistic Regression

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    In colorectal polyp prevention trials, estimation of the rate of recurrence of adenomas at the end of the trial may be complicated by dependent censoring, that is, time to follow-up colonoscopy and dropout may be dependent on time to recurrence. Assuming that the auxiliary variables capture the dependence between recurrence and censoring times, we propose to fit two working models with the auxiliary variables as covariates to define risk groups and then extend an existing weighted logistic regression method for independent censoring to each risk group to accommodate potential dependent censoring. In a simulation study, we show that the proposed method results in both a gain in efficiency and reduction in bias for estimating the recurrence rate. We illustrate the methodology by analyzing a recurrent adenoma dataset from a colorectal polyp prevention trial

    Potentials of Mean Force for Protein Structure Prediction Vindicated, Formalized and Generalized

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    Understanding protein structure is of crucial importance in science, medicine and biotechnology. For about two decades, knowledge based potentials based on pairwise distances -- so-called "potentials of mean force" (PMFs) -- have been center stage in the prediction and design of protein structure and the simulation of protein folding. However, the validity, scope and limitations of these potentials are still vigorously debated and disputed, and the optimal choice of the reference state -- a necessary component of these potentials -- is an unsolved problem. PMFs are loosely justified by analogy to the reversible work theorem in statistical physics, or by a statistical argument based on a likelihood function. Both justifications are insightful but leave many questions unanswered. Here, we show for the first time that PMFs can be seen as approximations to quantities that do have a rigorous probabilistic justification: they naturally arise when probability distributions over different features of proteins need to be combined. We call these quantities reference ratio distributions deriving from the application of the reference ratio method. This new view is not only of theoretical relevance, but leads to many insights that are of direct practical use: the reference state is uniquely defined and does not require external physical insights; the approach can be generalized beyond pairwise distances to arbitrary features of protein structure; and it becomes clear for which purposes the use of these quantities is justified. We illustrate these insights with two applications, involving the radius of gyration and hydrogen bonding. In the latter case, we also show how the reference ratio method can be iteratively applied to sculpt an energy funnel. Our results considerably increase the understanding and scope of energy functions derived from known biomolecular structures

    Solitary waves in the Nonlinear Dirac Equation

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    In the present work, we consider the existence, stability, and dynamics of solitary waves in the nonlinear Dirac equation. We start by introducing the Soler model of self-interacting spinors, and discuss its localized waveforms in one, two, and three spatial dimensions and the equations they satisfy. We present the associated explicit solutions in one dimension and numerically obtain their analogues in higher dimensions. The stability is subsequently discussed from a theoretical perspective and then complemented with numerical computations. Finally, the dynamics of the solutions is explored and compared to its non-relativistic analogue, which is the nonlinear Schr{\"o}dinger equation. A few special topics are also explored, including the discrete variant of the nonlinear Dirac equation and its solitary wave properties, as well as the PT-symmetric variant of the model

    Direct targets of the transcription factors ABA-Insensitive(ABI)4 and ABI5 reveal synergistic action by ABI4 and several bZIP ABA response factors

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    The plant hormone abscisic acid (ABA) is a key regulator of seed development. In addition to promoting seed maturation, ABA inhibits seed germination and seedling growth. Many components involved in ABA response have been identified, including the transcription factors ABA insensitive (ABI)4 and ABI5. The genes encoding these factors are expressed predominantly in developing and mature seeds, and are positive regulators of ABA mediated inhibition of seed germination and growth. The direct effects of ABI4 and ABI5 in ABA response remain largely undefined. To address this question, plants over-expressing ABI4 or ABI5 were used to allow identification of direct transcriptional targets. Ectopically expressed ABI4 and ABI5 conferred ABA-dependent induction of slightly over 100 genes in 11 day old plants. In addition to effector genes involved in seed maturation and reserve storage, several signaling proteins and transcription factors were identified as targets of ABI4 and/or ABI5. Although only 12% of the ABA- and ABI-dependent transcriptional targets were induced by both ABI factors in 11 day old plants, 40% of those normally expressed in seeds had reduced transcript levels in both abi4 and abi5 mutants. Surprisingly, many of the ABI4 transcriptional targets do not contain the previously characterized ABI4 binding motifs, the CE1 or S box, in their promoters, but some of these interact with ABI4 in electrophoretic mobility shift assays, suggesting that sequence recognition by ABI4 may be more flexible than known canonical sequences. Yeast one-hybrid assays demonstrated synergistic action of ABI4 with ABI5 or related bZIP factors in regulating these promoters, and mutant analyses showed that ABI4 and these bZIPs share some functions in plants

    Curriculum, intellectual property rights and open educational resources in British universities — and beyond

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    Is the curriculum in British universities being influenced by decisions about ownership of intellectual property rights (IPR) in ‘open educational resources’ (OERs) that are available online under Creative Commons licenses, free of charge? This paper provides the context for, describes and analyses three significant examples in British higher education where OERs are being created for use by academics and learners on campus or at a distance. OpenLearn and iTunes U, two of the British examples, are drawn from the Open University of the United Kingdom, which teaches over 200,000 undergraduate and graduate students almost entirely at a distance. The third example, OTTER, is at the University of Leicester, a campus university in England with about 7,000 distance learners. Both universities depend on government funding, student fees, research and entrepreneurial income. All three examples are funded indirectly by the British government, though OpenLearn has received substantial US foundation support as well. In presenting these examples, the questions arise of whether the projects are supply- or demand-driven, and of whether they are altruistic or not. Debate over intellectual property rights has influenced creation of the OERs and vice versa, but from these three examples it seems doubtful whether, as yet, OERs and IPR have significantly influenced British universities’ curriculum. The paper ends with discussion of how OERs created in British universities are influencing teaching and learning in other countries, as globalisation advances

    Multidetector row CT for imaging the paediatric tracheobronchial tree

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    The introduction of multidetector row computed tomography (MDCT) scanners has altered the approach to imaging the paediatric thorax. In an environment where the rapid acquisition of CT data allows general hospitals to image children instead of referring them to specialist paediatric centres, it is vital that general radiologists have access to protocols appropriate for paediatric applications. Thus a dramatic reduction in the delivered radiation dose is ensured with optimal contrast bolus delivery and timing, and inappropriate repetition of the scans is avoided. This article focuses on the main principles of volumetric CT imaging that apply generically to all MDCT scanners. We describe the reconstruction techniques for imaging the paediatric thorax and the low-dose protocols used in our institution on a 16-slice detector CT scanner. Examples of the commonest clinical applications are also given

    Association between reduced bronchodilatory effect of deep inspiration and loss of alveolar attachments

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    BACKGROUND: We have previously shown that the bronchodilatory effect of deep inspiration is attenuated in individuals with COPD. This study was designed to investigate whether the impairment in this effect is associated with loss of alveolar attachments. METHODS: We measured deep inspiration (DI)-induced bronchodilation in 15 individuals with and without COPD (67 ± 2.2 yrs of age, mean ± SEM) undergoing lobar resection for peripheral pulmonary nodule. Prior to surgery, we measured TLCO and determined the bronchodilatory effect of deep inspiration after constricting the airways with methacholine. The number of destroyed alveolar attachments, as well as airway wall area and airway smooth muscle area, were determined in tumor-free, peripheral lung tissue. RESULTS: The bronchodilatory effect of deep inspiration correlated inversely with the % destroyed attachments (r = -0.51, p = 0.05) and directly with the airway smooth muscle area (r = 0.59, p = 0.03), but not with the total wall area (r = 0.39, p = 0.15). CONCLUSION: We postulate that attenuation of airway stretch due to loss of alveolar attachments contributes to the loss of the bronchodilatory effect of lung inflation in COPD
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