1,214 research outputs found

    Actionable pharmacogenetic markers for prediction and prognosis in breast cancer

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    We would like to thank Professor Christian Scerri for advice and constructive discussions.Breast cancer is a heterogeneous disease that necessitates proper patient classification to direct surgery, pharmacotherapy, and radiotherapy. Despite patients within the same subgroup receiving similar pharmacotherapy, substantial variation in clinical outcomes is observed. Pharmacogenetic variations with direct effect on pharmacokinetics and pharmacodynamics play a central role in clinical outcomes. Pharmacogenetic markers associated with clinical outcome are known as biomarkers. They are termed prognostic biomarkers when their presence is associated with a specific clinical outcome. If the presence of such biomarkers guides treatment, they are termed predictive biomarkers. A number of pharmacogenetic markers have been described in relation to breast cancer pharmacotherapy both in the adjuvant and neoadjuvant setting. CYP2D6 allelic variants produce variable rates of tamoxifen metabolism and are associated with survival outcomes. Other biomarkers have been described in relation to other forms of endocrine therapy and trastuzumab. In neoadjuvant and adjuvant breast cancer chemotherapy, specific biomarkers were correlated with clinical outcomes and risk of drug toxicity. This review highlights key biomarkers in breast cancer pharmacotherapy with the potential of translating such study outcomes into clinical practice.peer-reviewe

    Design of ternary signals for MIMO identification in the presence of noise and nonlinear distortion

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    A new approach to designing sets of ternary periodic signals with different periods for multi-input multi-output system identification is described. The signals are pseudo-random signals with uniform nonzero harmonics, generated from Galois field GF(q), where q is a prime or a power of a prime. The signals are designed to be uncorrelated, so that effects of different inputs can be easily decoupled. However, correlated harmonics can be included if necessary, for applications in the identification of ill-conditioned processes. A design table is given for q les 31. An example is presented for the design of five uncorrelated signals with a common period N = 168 . Three of these signals are applied to identify the transfer function matrix as well as the singular values of a simulated distillation column. Results obtained are compared with those achieved using two alternative methods

    The influence of innate and adaptive immunity on Crohn’s disease severity

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    This article was originally published in a special issue, entitled: "Inflammatory Bowel Disease", Edited by Nancy Louis, Emory University, USA and Ostanin Dmitry Vladimirovich, Louisiana State University Health Sciences Center, USAStricturing and penetrating disease are classified as severe Crohn’s disease types and are frequently associated with an increased risk for bowel surgery. Research has shown that early treatment with aggressive immunosuppression (including biological and thiopurine therapies – the so-called “top-down approach”) results in a diminished risk of developing these complicated disease types. However, these therapies carry significant risks and cost. Being able to predict which patients are at an increased risk of developing severe Crohn’s disease may enable us to treat patients individually, with the aggressive “top-down approach” started at diagnosis in patients with a significantly increased risk of developing complicated disease types. Defects of innate and adaptive immunity both play a role in Crohn’s disease pathophysiology. Identifying whether defects of innate immunity (through gene mutations) or adaptive immunity (through antibodies to microbial antigens) are associated with stricturing/penetrating disease types may enable us to predict the course of the disease and therefore decide on who would benefit most from the “top-down approach”. This review discusses the role of NOD2 and other gene polymorphisms in predicting Crohn’s disease severity. It also highlights the evidence linking the role of the various antibodies involved in adaptive immunity (ASCA, OmpC, GM-CSF) and complicated Crohn’s disease types.peer-reviewe

    Orthodontists and the thyroid gland

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    Fresh stirrings among statisticians: statistical commentary

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    Practical synthesis of ternary sequences for system identification

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    Several issues related to the practical synthesis of ternary sequences with specified spectra are addressed in this paper. Specifically, sequences with harmonic multiples of two and three suppressed are studied, given their relevance to system identification applications. In particular, the effect of non-uniform Digital to Analog Converter (DAC) levels on the spectral properties of the generated signal is analyzed. It is analytically shown that the DAC non-uniform levels result in degraded harmonic suppression performance. Moreover, a new approach is proposed for designing ternary sequences, which is flexible and can be adapted to suit different requirements. The resulting sequences, denoted as randomized constrained sequences, are compared to direct sequences already proposed in the literature. The approach is validated by numerical simulations and experimental results, showing the potential to achieve harmonic suppression performance of approximately 100 dB

    Retinal Wave Behavior through Activity- Dependent Refractory Periods

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    In the developing mammalian visual system, spontaneous retinal ganglion cell (RGC) activity contributes to and drives several aspects of visual system organization. This spontaneous activity takes the form of spreading patches of synchronized bursting that slowly advance across portions of the retina. These patches are non-repeating and tile the retina in minutes. Several transmitter systems are known to be involved, but the basic mechanism underlying wave production is still not well-understood. We present a model for retinal waves that focuses on acetylcholine mediated waves but whose principles are adaptable to other developmental stages. Its assumptions are that a) spontaneous depolarizations of amacrine cells drive wave activity; b) amacrine cells are locally connected, and c) cells receiving more input during their depolarization are subsequently less responsive and have longer periods between spontaneous depolarizations. The resulting model produces waves with non-repeating borders and randomly distributed initiation points. The wave generation mechanism appears to be chaotic and does not require neural noise to produce this wave behavior. Variations in parameter settings allow the model to produce waves that are similar in size, frequency, and velocity to those observed in several species. Our results suggest that retinal wave behavior results from activity-dependent refractory periods and that the average velocity of retinal waves depends on the duration a cell is excitatory: longer periods of excitation result in slower waves. In contrast to previous studies, we find that a single layer of cells is sufficient for wave generation. The principles described here are very general and may be adaptable to the description of spontaneous wave activity in other areas of the nervous system

    The evaluation of brine prospects and the requirement for modifications to filing standards

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    The recent increase in demand for lithium has led to the development of new brine prospects, particularly in the Central Andes. The brines are hosted in closed basin aquifers of two types: mature, halite dominant, and immature, clastic dominant. The estimate of elemental resources in these salars depends on a detailed knowledge of aquifer geometry, porosity, and brine grade. The geometry of the aquifers can be evaluated by classical geophysical and drilling techniques, but because the resource is a fluid, with the attendant problems of in-aquifer mixing and reorganization, existing codes for filing resource and reserve estimates need modification. Total porosity is relatively straightforward to measure, but effective porosity and specific yield, which are required to estimate the resource, are more difficult. Recovery factors are low compared with most metalliferous and industrial mineral deposits due to reliance on pumping of the brine from wells for extraction. These and related issues lead us to believe that modifications to the existing standards for reporting mineral resources and reserves are required for these prospects
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