13,877 research outputs found

    On Variants of CM-triviality

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    We introduce a generalization of CM-triviality relative to a fixed invariant collection of partial types, in analogy to the Canonical Base Property defined by Pillay, Ziegler and Chatzidakis which generalizes one-basedness. We show that, under this condition, a stable field is internal to the family, and a group of finite Lascar rank has a normal nilpotent subgroup such that the quotient is almost internal to the family

    Reducing systematic review workload using text mining: opportunities and pitfalls

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    This EAHIL workshop focussed on three applications of text mining to assist with screening citations for systematic reviews, and encouraged participants to discuss issues affecting their adoption. This paper outlines these applications and summarises the factors raised by participants in relation to their uptake. Key aspects to uptake include having an accepted advantage over existing approaches, coupled with training and user support

    Potent and selective inhibitors of histone deacetylase-3 containing chiral oxazoline capping groups and a N-(2-Aminophenyl)-benzamide binding unit

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    A novel series of potent chiral inhibitors of histone deacetylase (HDAC) is described that contains an oxazoline capping group and a N-(2-aminophenyl)-benzamide unit. Among several new inhibitors of this type exhibiting Class I selectivity and potent inhibition of HDAC3-NCoR2, in vitro assays for the inhibition of HDAC1, HDAC2, and HDAC3-NCoR2 by N-(2-aminophenyl)-benzamide 15k gave respective IC50 values of 80, 110, and 6 nM. Weak inhibition of all other HDAC isoforms (HDAC4, 5, 6, 7, and 9: IC50 > 100 000 nM; HDAC8: IC50 = 25 000 nM; HDAC10: IC50 > 4000 nM; HDAC11: IC50 > 2000 nM) confirmed the Class I selectivity of 15k. 2-Aminoimidazolinyl, 2-thioimidazolinyl, and 2-aminooxazolinyl units were shown to be effective replacements for the pyrimidine ring present in many other 2-(aminophenyl)-benzamides previously reported, but the 2-aminooxazolinyl unit was the most potent in inhibiting HDAC3-NCoR2. Many of the new HDAC inhibitors showed higher solubilities and lower binding to human serum albumin than that of Mocetinostat. Increases in histone H3K9 acetylation in the human cell lines U937 and PC-3 was observed for all three oxazolinyl inhibitors evaluated; those HDAC inhibitors also lowered cyclin E expression in U937 cells but not in PC-3 cells, indicating underlying differences in the mechanisms of action of the inhibitors on those two cell lines

    Principled Versus Statistical Thinking in Diagnosis and Treatment of Stroke

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    Medical science is now synonymous with probability-based statistics. Statistics deals with a group; it does not need probability theory. Probability theory is consistent with the worldview that the universe is infinite, bounded, random, and governed by chance. Its logic is binary, its geometry is Cartesian, its rules offer a scientific method by which hypotheses may be tested. Clinical trials and even hypothesis testing at the bedside have nestled into the probability foundation. As a result, scientific “evidence” now appears only through the lens of probability theory. Because there is no definitive truth in the worldview of probability theory, the truth of evidence lies in probabilities only. The probabilistic view of science has a firm impact on the practice of medicine and implications for medical–legal decisions

    2d Gauge Theories and Generalized Geometry

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    We show that in the context of two-dimensional sigma models minimal coupling of an ordinary rigid symmetry Lie algebra g\mathfrak{g} leads naturally to the appearance of the "generalized tangent bundle" TMTMTM\mathbb{T}M \equiv TM \oplus T^*M by means of composite fields. Gauge transformations of the composite fields follow the Courant bracket, closing upon the choice of a Dirac structure DTMD \subset \mathbb{T}M (or, more generally, the choide of a "small Dirac-Rinehart sheaf" D\cal{D}), in which the fields as well as the symmetry parameters are to take values. In these new variables, the gauge theory takes the form of a (non-topological) Dirac sigma model, which is applicable in a more general context and proves to be universal in two space-time dimensions: A gauging of g\mathfrak{g} of a standard sigma model with Wess-Zumino term exists, \emph{iff} there is a prolongation of the rigid symmetry to a Lie algebroid morphism from the action Lie algebroid M×gMM \times \mathfrak{g}\to M into DMD\to M (or the algebraic analogue of the morphism in the case of D\cal{D}). The gauged sigma model results from a pullback by this morphism from the Dirac sigma model, which proves to be universal in two-spacetime dimensions in this sense.Comment: 22 pages, 2 figures; To appear in Journal of High Energy Physic

    A Study of Initialization in Linux and OpenBSD

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    The code that initializes a system can be notoriously difficult to understand. In secure systems, initialization is critical for establishing a starting state that is secure. This paper explores two architectures used for bringing an operating system to its initial state, once the operating system gains control from the boot loader. Specifically, the ways in which the OpenBSD and Linux operating systems handle initialization are dissected

    Generalized N = 2 Super Landau Models

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    We generalize previous results for the superplane Landau model to exhibit an explicit worldline N = 2 supersymmetry for an arbitrary magnetic field on any two-dimensional manifold. Starting from an off-shell N = 2 superfield formalism, we discuss the quantization procedure in the general case characterized by two independent potentials on the manifold and show that the relevant Hamiltonians are factorizable. In the restricted case when both the Gauss curvature and the magnetic field are constant over the manifold and, as a consequence, the underlying potentials are related, the Hamiltonians admit infinite series of factorization chains implying the integrability of the associated systems. We explicitly determine the spectrum and eigenvectors for the particular model with CP^1 as the bosonic manifold.Comment: 26 page

    Exploiting biological and physical determinants of radiotherapy toxicity to individualise treatment.

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    This is the final version of the article. It first appeared from the British Institute of Radiology via http://dx.doi.org/10.1259/bjr.20150172The recent advances in radiation delivery can improve tumour control probability and reduce treatment related toxicity. The use of intensity-modulated radiotherapy (IMRT) in particular can reduce normal tissue toxicity, an objective in its own right, and can allow safe dose escalation in selected cases. Ideally IMRT should be combined with image guidance to verify the position of the target, since patients, target and organs at risk can move day-to-day. Daily image guidance scans can be used to identify the position of normal tissue structures, and potentially to compute the daily delivered dose. Fundamentally, it is still the tolerance of the normal tissues which limits radiotherapy dose and therefore tumour control. However, the dose response relationships for both tumour and normal tissues are relatively steep, meaning that small dose differences can translate into clinically relevant improvements. Differences exist between individuals in the severity of toxicity experienced for a given dose of radiotherapy. Some of this difference may be the result of differences between the planned dose and the accumulated dose (DA). However, some may be due to intrinsic differences in radiosensitivity of the normal tissues between individuals. This field has been developing rapidly, with the demonstration of definite associations between genetic polymorphisms and variation in toxicity recently described. It might be possible to identify more resistant patients who would be suitable for dose escalation, as well as more sensitive patients for whom toxicity could be reduced or avoided. Daily differences in delivered dose have been investigated within the VoxTox research programme, using the rectum as an example organ at risk. In prostate cancer patients receiving curative radiotherapy, considerable daily variation in rectal position and dose can be demonstrated, although the median position matches the planning scan well. Overall, in 10 patients, the mean difference between planned and accumulated rectal equivalent uniform doses (EUDs) was -2.7 Gy (5%), and a dose reduction was seen in 7/10 cases. If dose escalation were performed to take rectal dose back to the planned level, this should increase the mean tumour control probability (TCP) (as biochemical progression-free survival) by 5%. Combining radiogenomics with individual estimates of DA might identify almost half of patients undergoing radical radiotherapy who might benefit from either dose escalation, suggesting improved tumour cure, or reduced toxicity, or both.JS is supported by Cancer Research UK through the Cambridge Cancer Centre. NGB is supported by the NIHR Cambridge Biomedical Research Centre. The VoxTox Research Programme is funded by Cancer Research UK

    Comparing pregnancy outcomes in patients with criteria and non-criteria autoimmune disease: A systematic review

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    Background: Not all patients fulfil criteria for specific autoimmune rheumatic diseases (ARDs) and are then defined as having non-criteria (nc)ARD. It is uncertain whether well-recognised associations with adverse pregnancy outcomes in patients with criteria ARD also exist in patients with ncARD or undifferentiated connective tissue disease (UCTD). Therefore, we undertook a systematic review of the prevalence of adverse pregnancy outcomes in various ncARD and UCTD compared with criteria ARD to identify whether there are increased risks and to examine for any benefits of treatment. // Methods: This study was conducted in accordance with the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. A systematic literature review was performed using online databases including Medline and PubMed from inception to the beginning of April 2021 using appropriate keywords for various ARD and pregnancy outcomes. // Results: After screening 665 articles, 36 articles were chosen for full text review and 15 selected for final analysis. There were eight studies of nc antiphospholipid syndrome (APS) of more than 7000 pregnancies and seven studies of UCTD of more than 1000 pregnancies. No studies of any other ncARD in pregnancy were identified. We found that patients with either ncAPS or UCTD seem to have an increased burden of poor pregnancy outcomes compared with the general population. Despite the heterogeneity and poor quality of the studies, we also noted that ncAPS and criteria APS patients may have similar rates of obstetric complications with standard and/or non-standard APS treatment regimens. // Conclusion: Our findings of increased risks of poor pregnancy outcomes in patients with ncAPS or UCTD will be helpful for pre-pregnancy counselling and management of these patients in pregnancy and support their referral to specialist obstetric-rheumatology and obstetric-haematology clinics
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