93 research outputs found

    Selective recruitment designs for improving observational studies using electronic health records

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    Large‐scale electronic health records (EHRs) present an opportunity to quickly identify suitable individuals in order to directly invite them to participate in an observational study. EHRs can contain data from millions of individuals, raising the question of how to optimally select a cohort of size n from a larger pool of size N . In this article, we propose a simple selective recruitment protocol that selects a cohort in which covariates of interest tend to have a uniform distribution. We show that selectively recruited cohorts potentially offer greater statistical power and more accurate parameter estimates than randomly selected cohorts. Our protocol can be applied to studies with multiple categorical and continuous covariates. We apply our protocol to a numerically simulated prospective observational study using an EHR database of stable acute coronary disease patients from 82 089 individuals in the U.K. Selective recruitment designs require a smaller sample size, leading to more efficient and cost‐effective studies

    A combinatorial approach to optimal designs.

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    PhDA typical problem in experimental design theory is to find a block design in a class that is optimal with respect to some criteria, which are usually convex functions of the Laplacian eigenvalues. Although this question has a statistical background, there are overlaps with graph and design theory: some of the optimality criteria correspond to graph properties and designs considered ‘nice’ by combinatorialists are often optimal. In this thesis we investigate this connection from a combinatorial point of view. We extend a result on optimality of some generalized polygons, in particular the generalized hexagon and octagon, to a third optimality criterion. The E-criterion is equivalent with the graph theoretical problem of maximizing the algebraic connectivity. We give a new upper bound for regular graphs and characterize a class of E-optimal regular graph designs (RGDs). We then study generalized hexagons as block designs and prove some properties of the eigenvalues of the designs in that class. Proceeding to higher-dimensional geometries, we look at projective spaces and find optimal designs among two-dimensional substructures. Some new properties of Grassmann graphs are proved. Stepping away from the background of geometries, we study graphs obtained from optimal graphs by deleting one or several edges. This chapter highlights the currently available methods to compare graphs on the A- and D-criteria. The last chapter is devoted to designs to which a number of blocks are added. Cheng showed that RGDs are A- and D-optimal if the number of blocks is large enough for which we give a bound and characterize the best RGDs in terms of their underlying graphs. We then present the results of an exhaustive computer search for optimal RGDs for up to 18 points. The search produced examples supporting several open conjectures

    An Automated System for Strain Engineering and Straintronics of 2D Materials

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    This work presents an automated three-point bending apparatus that can be used to study strain engineering and straintronics in 2D materials. This work benchmarks the system by reporting reproducible strain tuned micro-reflectance, Raman, and photoluminescence spectra for monolayer molybdenum disulfide (MoS2). These results are in good agreement with reported literature using conventional bending apparatus. This work further utilizes the system to automate strain investigations of straintronic devices by measuring the piezoresistive effect and the strain effect on photoresponse in an MoS2 electrical device. The details of the construction of the straightforward system are given and it is anticipated that it can be easily implemented for study of strain engineering and straintronics in a wide variety of 2D material systems

    Genome-wide reconstitution of chromatin transactions reveals that RSC preferentially disrupts H2AZ-containing nucleosomes

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    Chromatin transactions are typically studied in vivo, or in vitro using artificial chromatin lacking the epigenetic complexity of the natural material. Attempting to bridge the gap between these approaches, we established a system for isolating the yeast genome as a library of mononucleosomes harboring the natural epigenetic signature, suitable for biochemical manipulation. Combined with deep sequencing, this library was used to investigate the stability of individual nucleosomes and, as proof of principle, the nucleosome preference of the chromatin remodeling complex, RSC. This approach uncovered a distinct preference of RSC for nucleosomes derived from regions with a high density of histone variant H2AZ, and this preference is indeed markedly diminished using nucleosomes from cells lacking H2AZ. The preference for H2AZ remodeling/nucleosome ejection can also be reconstituted with recombinant nucleosome arrays. Together, our data indicate that, despite being separated from their genomic context, individual nucleosomes can retain their original identity as promoter- or transcription start site (TSS)-nucleosomes. Besides shedding new light on substrate preference of the chromatin remodeler RSC, the simple experimental system outlined here should be generally applicable to the study of chromatin transactions

    Primary central nervous system lymphoma presenting as a pure third ventricular lesion: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Primary central nervous system lymphomas are infrequently occurring lymphomas that account for only 0.3-1.5% of all intra-cranial neoplasms in patients without acquired immune deficiency syndrome. However, a pure third ventricle lymphoma is extremely rare. Here, we discuss the similar radiological appearances of lesions localized in the third ventricle and the importance of accurately diagnosing primary central nervous system lymphomas for favorable treatment outcomes.</p> <p>Case presentation</p> <p>A 38-year-old Caucasian man from Turkey presented with a severe headache lasting for three months that failed to respond to any medication. Both severity and duration of the symptoms increased gradually, resulting in vomiting, nausea and gait disturbance that accompanied the headache for three weeks. Neuro-imaging studies showed a lesion located solely in the third ventricle, resulting in partial obstruction of the foramen of Monro. The pre-operative diagnosis was a colloid cyst. Following the surgical procedure, the results of pathological and immunochemical assays revealed that the pre-operative diagnosis was incorrect and that the lesion was a primary central system lymphoma.</p> <p>Conclusion</p> <p>Pure third ventricle lymphomas are extremely rare and are exceptionally localized. It is important to be aware of, and to differentiate between, other possible third ventricular lesions that may mimic the same radiological appearance. Accurate diagnosis is necessary for selecting appropriate treatment modalities.</p

    Estimating the prevalence of functional exonic splice regulatory information

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