439 research outputs found

    Monte Carlo Euler approximations of HJM term structure financial models

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    We present Monte Carlo-Euler methods for a weak approximation problem related to the Heath-Jarrow-Morton (HJM) term structure model, based on \Ito stochastic differential equations in infinite dimensional spaces, and prove strong and weak error convergence estimates. The weak error estimates are based on stochastic flows and discrete dual backward problems, and they can be used to identify different error contributions arising from time and maturity discretization as well as the classical statistical error due to finite sampling. Explicit formulas for efficient computation of sharp error approximation are included. Due to the structure of the HJM models considered here, the computational effort devoted to the error estimates is low compared to the work to compute Monte Carlo solutions to the HJM model. Numerical examples with known exact solution are included in order to show the behavior of the estimates

    Interaction of cysteine proteinases with recombinant kininogen domain 2, expressed in Escherichia coli

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    AbstractThe calpain-binding domain 2 of the kininogens, the major plasma inhibitors of cysteine proteinases, was expressed in Escherichia coli. Expression of soluble protein was optimal at 15°C and was augmented by growing the bacteria in sorbitol and betaine. The recombinant domain showed high affinity (Ki 0.3–1 nM) for cathepsin L and papain, and a somewhat lower affinity (Ki∼ 15 nM) for calpain. The binding to cathepsin H was substantially weaker, and no inhibition of actinidin and cathepsin B was detected. The affinity for cathepsin L was comparable to that reported for the domain isolated from plasma L-kininogen, whereas the affinities for papain and calpain were about tenfold lower. The latter difference may be due to the recombinant domain being nonglycosylated

    Insights Gained From a Re-analysis of Five Improvement Cases in Healthcare Integrating System Dynamics Into Action Research

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    Background Healthcare is complex with multi-professional staff and a variety of patient care pathways. Time pressure and minimal margins for errors, as well as tension between hierarchical power and the power of the professions, make it challenging to implement new policies or procedures. This paper explores five improvement cases in healthcare integrating system dynamics (SD) into action research (AR), aiming to identify methodological aspects of how this integration supported multi-professional groups to discover workable solutions to work-related challenges. Methods This re-analysis was conducted by a multi-disciplinary research group using an iterative abductive approach applying qualitative analysis to structure and understand the empirical material. Frameworks for consultancy assignments/client projects were used to identify case project stages (workflow steps) and socio-analytical questions were used to bridge between the AR and SD perspectives. Results All studied cases began with an extensive AR-inspired inventory of problems/objectives and ended with an SDfacilitated experimental phase where mutually agreed solutions were tested in silico. Time was primarily divided between facilitated group discussions during meetings and modelling work between meetings. Work principles ensured that the voice of each participant was heard, inspired engagement, interaction, and exploratory mutual learning activities. There was an overall pattern of two major divergent and convergent phases, as each group moved towards a mutually developed point of reference for their problem/objective and solution, a case-specific multi-professional knowledge repository. Conclusion By integrating SD into AR, more favourable outcomes for the client organization may be achieved than when applying either approach in isolation. We found that SD provided a platform that facilitated experiential learning in the AR process. The identified results were calibrated to local needs and circumstances, and compared to traditional top-down implementation for change processes, improved the likelihood of sustained actualisation.publishedVersio

    Insights gained from a systematic reanalysis of a successful model-facilitated change process in health care

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    Health care is a complex system with multiprofessional staff and multiple patient care pathways. Time pressure and minimal margins for error make it challenging to implement new policies or procedures, no matter how desirable. Changes in health care also requires the participation of the staff. System dynamics (SD) simulations can lead to shared systems understanding and allows for the development and testing of new scenarios in silico before implementing solutions. However, research shows that the actual implementation rate of simulations is low. This paper presents a reanalysis of a successful change project in health care combining SD principles with basic action research (AR) premises. The analysis was done by a multidisciplinary research group using qualitative methodology and identifies that a fruitful combination of AR inquiry and SD modelling potentially can improve implementation rates.publishedVersio

    Numerical Analysis of the Non-uniform Sampling Problem

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    We give an overview of recent developments in the problem of reconstructing a band-limited signal from non-uniform sampling from a numerical analysis view point. It is shown that the appropriate design of the finite-dimensional model plays a key role in the numerical solution of the non-uniform sampling problem. In the one approach (often proposed in the literature) the finite-dimensional model leads to an ill-posed problem even in very simple situations. The other approach that we consider leads to a well-posed problem that preserves important structural properties of the original infinite-dimensional problem and gives rise to efficient numerical algorithms. Furthermore a fast multilevel algorithm is presented that can reconstruct signals of unknown bandwidth from noisy non-uniformly spaced samples. We also discuss the design of efficient regularization methods for ill-conditioned reconstruction problems. Numerical examples from spectroscopy and exploration geophysics demonstrate the performance of the proposed methods

    Prostate specific antigen concentration at age 60 and death or metastasis from prostate cancer: case-control study

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    Objective To determine the relation between concentrations of prostate specific antigen at age 60 and subsequent diagnosis of clinically relevant prostate cancer in an unscreened population to evaluate whether screening for prostate cancer and chemoprevention could be stratified by risk

    On the pp-supports of a holonomic D\mathcal{D}-module

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    For a smooth variety YY over a perfect field of positive characteristic, the sheaf DYD_Y of crystalline differential operators on YY (also called the sheaf of PDPD-differential operators) is known to be an Azumaya algebra over TY,T^*_{Y'}, the cotangent space of the Frobenius twist YY' of Y.Y. Thus to a sheaf of modules MM over DYD_Y one can assign a closed subvariety of TY,T^*_{Y'}, called the pp-support, namely the support of MM seen as a sheaf on TY.T^*_{Y'}. We study here the family of pp-supports assigned to the reductions modulo primes pp of a holonomic D\mathcal{D}-module. We prove that the Azumaya algebra of differential operators splits on the regular locus of the pp-support and that the pp-support is a Lagrangian subvariety of the cotangent space, for pp large enough. The latter was conjectured by Kontsevich. Our approach also provides a new proof of the involutivity of the singular support of a holonomic D\mathcal{D}-module, by reduction modulo p.p.Comment: The article has been rewritten with much improved exposition as well as some additional results, e.g. Corollary 6.3.1. This is the final version, accepted for publication in Inventiones Mathematica

    Pancreas and islet cell transplantation

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    Currently, for the patient with type 1 diabetes, a definitive treatment without resorting to the use of exogenous insulin can be achieved only with pancreas or islet cell transplantation. These means of restoring β-cell mass can completely maintain essentially normal long-term glucose homeostasis, although the need for powerful immunosuppressive regimens limits their application to only a subgroup of adult patients. Apart from the shortage of donors that has limited all kinds of transplantation, however, the widespread use of β-cell replacement has been precluded until recently by the drawbacks associated with both organ and islet cell transplantation. Although the study of recurrence of diabetes has generated attention, the fundamental obstacle to pancreas and islet transplantation has been, and remains, the alloimmune response. With a better elucidation of the mechanisms of alloengraftment achieved during the last 3 years, the stage has been set for further advances
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