92 research outputs found

    Direct and Inverse Computation of Jacobi Matrices of Infinite Homogeneous Affine I.F.S

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    We introduce a new set of algorithms to compute Jacobi matrices associated with measures generated by infinite systems of iterated functions. We demonstrate their relevance in the study of theoretical problems, such as the continuity of these measures and the logarithmic capacity of their support. Since our approach is based on a reversible transformation between pairs of Jacobi matrices, we also discuss its application to an inverse / approximation problem. Numerical experiments show that the proposed algorithms are stable and can reliably compute Jacobi matrices of large order.Comment: 20 pages 6 figure

    High resolution melting analysis for a rapid identification of heterozygous and homozygous sequence changes in the MUTYH gene

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    Background: MUTYH-associated polyposis (MAP) is an autosomal recessive form of intestinal polyposis predisposing to colorectal carcinoma. High resolution melting analysis (HRMA) is a mutation scanning method that allows detection of heterozygous sequence changes with high sensitivity, whereas homozygosity for a nucleotide change may not lead to significant curve shape or melting temperature changes compared to homozygous wildtype samples. Therefore, HRMA has been mainly applied to the detection of mutations associated with autosomal dominant or X-linked disorders, while applications to autosomal recessive conditions are less common. Methods: MUTYH coding sequence and UTRs were analyzed by both HRMA and sequencing on 88 leukocyte genomic DNA samples. Twenty-six samples were also examined by SSCP. Experiments were performed both with and without mixing the test samples with wild-type DNA. Results: The results show that all MUTYH sequence variations, including G > C and A > T homozygous changes, can be reliably identified by HRMA when a condition of artificial heterozygosity is created by mixing test and reference DNA. HRMA had a sensitivity comparable to sequencing and higher than SSCP. Conclusions: The availability of a rapid and inexpensive method for the identification of MUTYH sequence variants is relevant for the diagnosis of colorectal cancer susceptibility, since the MAP phenotype is highly variable

    Health-related quality of life following a clinical weight loss intervention among overweight and obese adults: intervention and 24 month follow-up effects

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    BACKGROUND: Despite a growing literature on the efficacy of behavioral weight loss interventions, we still know relatively little about the long terms effects they have on HRQL. Therefore, we conducted a study to investigate the immediate post-intervention (6 months) and long-term (12 and 24 months) effects of clinically based weight management programs on HRQL. METHODS: We conducted a randomized clinical trial in which all participants completed a 6 month clinical weight loss program and were randomized into two 6-month extended care groups. Participants then returned at 12 and 24 months for follow-up assessments. A total of 144 individuals (78% women, M age = 50.2 (9.2) yrs, M BMI = 32.5 (3.8) kg/m(2)) completed the 6 month intervention and 104 returned at 24 months. Primary outcomes of weight and HRQL using the SF-36 were analyzed using multivariate repeated measures analyses. RESULTS: There was complete data on 91 participants through the 24 months of the study. At baseline the participants scored lower than U.S. age-specific population norms for bodily pain, vitality, and mental health. At the completion of the 6 month clinical intervention there were increases in the physical and mental composite measures as well as physical functioning, general health, vitality, and mental health subscales of the SF-36. Despite some weight regain, the improvements in the mental composite scale as well as the physical functioning, vitality, and mental health subscales were maintained at 24 months. There were no significant main effects or interactions by extended care treatment group or weight loss group (whether or not they maintained 5% loss at 24 months). CONCLUSION: A clinical weight management program focused on behavior change was successful in improving several factors of HRQL at the completion of the program and many of those improvements were maintained at 24 months. Maintaining a significant weight loss (> 5%) was not necessary to have and maintain improvements in HRQL

    Quadrature Strategies for Constructing Polynomial Approximations

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    Finding suitable points for multivariate polynomial interpolation and approximation is a challenging task. Yet, despite this challenge, there has been tremendous research dedicated to this singular cause. In this paper, we begin by reviewing classical methods for finding suitable quadrature points for polynomial approximation in both the univariate and multivariate setting. Then, we categorize recent advances into those that propose a new sampling approach and those centered on an optimization strategy. The sampling approaches yield a favorable discretization of the domain, while the optimization methods pick a subset of the discretized samples that minimize certain objectives. While not all strategies follow this two-stage approach, most do. Sampling techniques covered include subsampling quadratures, Christoffel, induced and Monte Carlo methods. Optimization methods discussed range from linear programming ideas and Newton's method to greedy procedures from numerical linear algebra. Our exposition is aided by examples that implement some of the aforementioned strategies

    Genetic screening of Fabry patients with EcoTILLING and HRM technology

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    <p>Abstract</p> <p>Background</p> <p>Anderson-Fabry disease (FD) is caused by a deficit of the α-galactosidase A enzyme which leads to the accumulation of complex sphingolipids, especially globotriaosylceramide (Gb3), in all the cells of the body, causing the onset of a multi-systemic disease with poor prognosis in adulthood. In this article, we describe two alternative methods for screening the <it>GLA </it>gene which codes for the α-galactosidase A enzyme in subjects with probable FD in order to test analysis strategies which include or rely on initial pre-screening.</p> <p>Findings</p> <p>We analyzed 740 samples using EcoTILLING, comparing two mismatch-specific<ul/>endonucleases, CEL I and ENDO-1, while conducting a parallel screening of the same samples using HRM (High Resolution Melting). Afterwards, all samples were subjected to direct sequencing. Overall, we identified 12 different genetic variations: -10C>T, -12G>A, -30G>A, IVS2-76_80del5, D165H, C172Y, IVS4+16A>G, IVS4 +68 A>G, c.718_719delAA, D313Y, IVS6-22C>T, G395A. This was consistent with the high genetic heterogeneity found in FD patients and carriers. All of the mutations were detected by HRM, whereas 17% of the mutations were not found by EcoTILLING. The results obtained by EcoTILLING comparing the CEL I and ENDO-1 endonucleases were perfectly overlapping.</p> <p>Conclusion</p> <p>On the basis of its simplicity, flexibility, repeatability, and sensitivity, we believe that<ul/>HRM analysis of the <it>GLA </it>gene is a reliable presequencing screening tool. This method can be applied to any genomic feature to identify known and unknown genetic alterations, and it is ideal for conducting screening and population studies.</p

    The role of whole brain radiation therapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline

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    QUESTION: Should patients with newly-diagnosed metastatic brain tumors undergo open surgical resection versus whole brain radiation therapy (WBRT) and/or other treatment modalities such as radiosurgery, and in what clinical settings? TARGET POPULATION: These recommendations apply to adults with a newly diagnosed single brain metastasis amenable to surgical resection. RECOMMENDATIONS: Surgical resection plus WBRT versus surgical resection alone Level 1 Surgical resection followed by WBRT represents a superior treatment modality, in terms of improving tumor control at the original site of the metastasis and in the brain overall, when compared to surgical resection alone. Surgical resection plus WBRT versus SRS + or - WBRT Level 2 Surgical resection plus WBRT, versus stereotactic radiosurgery (SRS) plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (\u3e3 cm) or for those causing significant mass effect (\u3e1 cm midline shift). Level 3 Underpowered class I evidence along with the preponderance of conflicting class II evidence suggests that SRS alone may provide equivalent functional and survival outcomes compared with resection + WBRT for patients with single brain metastases, so long as ready detection of distant site failure and salvage SRS are possible. Note The following question is fully addressed in the WBRT guideline paper within this series by Gaspar et al. Given that the recommendation resulting from the systematic review of the literature on this topic is also highly relevant to the discussion of the role of surgical resection in the management of brain metastases, this recommendation has been included below
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