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Search Results: 1 - 10 of 486950 matches for " Thomas A. Sellers "
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Regular Multivitamin Supplement Use, Single Nucleotide Polymorphisms in ATIC, SHMT2, and SLC46A1, and Risk of Ovarian Carcinoma
Linda E. Kelemen,Qinggang Wang,Robert A. Vierkant,Julie M. Cunningham,Ernest K. Amankwah,Thomas A. Sellers
Frontiers in Genetics , 2012, DOI: 10.3389/fgene.2012.00033
Abstract: ATIC, SHMT2, and SLC46A1 have essential roles in one-carbon (1-C) transfer. The authors examined whether associations between ovarian carcinoma and 15 variants in these genes are modified by regular multivitamin use, a source of 1-C donors, among Caucasian participants from two US case–control studies. Using a phased study design, variant-by-multivitamin interactions were tested, and associations between variants and ovarian carcinoma were reported stratified by multivitamin supplement use. Per-allele risk associations were modified by multivitamin use at six variants among 655 cases and 920 controls (Phase 1). In a larger sample of 968 cases and 1,265 controls (Phases 1 and 2), interactions were significant (P ≤ 0.03) for two variants, particularly among regular multivitamin users: ATIC rs7586969 [odds ratio (OR) = 0.7, 95% confidence interval (CI) = 0.6–0.9] and ATIC rs16853834 (OR = 1.5, 95% CI = 1.1–2.0). The two ATIC single nucleotide polymorphisms (SNPs) did not share the same haplotype; however, the haplotypes they comprised mirrored their SNP risk associations among regular multivitamin supplement users. A multi-variant analysis was also performed by comparing the observed likelihood ratio test statistic from adjusted models with and without the two ATIC variant-by-multivitamin interaction terms with a null distribution of test statistics generated by permuting case status 10,000 times. The corresponding observed P value of 0.001 was more extreme than the permutation-derived P value of 0.009, suggesting rejection of the null hypothesis of no association. In summary, there is little statistical evidence that the 15 variants are independently associated with risk of ovarian carcinoma. However, the statistical interaction of ATIC variants with regular multivitamin intake, when evaluated at both the SNP and gene level, may support these findings as relevant to ovarian health and disease processes.
Allele-Specific Amplification in Cancer Revealed by SNP Array Analysis
Thomas LaFramboise,Barbara A Weir,Xiaojun Zhao,Rameen Beroukhim,Cheng Li,David Harrington,William R Sellers,Matthew Meyerson
PLOS Computational Biology , 2005, DOI: 10.1371/journal.pcbi.0010065
Abstract: Amplification, deletion, and loss of heterozygosity of genomic DNA are hallmarks of cancer. In recent years a variety of studies have emerged measuring total chromosomal copy number at increasingly high resolution. Similarly, loss-of-heterozygosity events have been finely mapped using high-throughput genotyping technologies. We have developed a probe-level allele-specific quantitation procedure that extracts both copy number and allelotype information from single nucleotide polymorphism (SNP) array data to arrive at allele-specific copy number across the genome. Our approach applies an expectation-maximization algorithm to a model derived from a novel classification of SNP array probes. This method is the first to our knowledge that is able to (a) determine the generalized genotype of aberrant samples at each SNP site (e.g., CCCCT at an amplified site), and (b) infer the copy number of each parental chromosome across the genome. With this method, we are able to determine not just where amplifications and deletions occur, but also the haplotype of the region being amplified or deleted. The merit of our model and general approach is demonstrated by very precise genotyping of normal samples, and our allele-specific copy number inferences are validated using PCR experiments. Applying our method to a collection of lung cancer samples, we are able to conclude that amplification is essentially monoallelic, as would be expected under the mechanisms currently believed responsible for gene amplification. This suggests that a specific parental chromosome may be targeted for amplification, whether because of germ line or somatic variation. An R software package containing the methods described in this paper is freely available at http://genome.dfci.harvard.edu/~tlaframb?/PLASQ.
A Latent Model for Prioritization of SNPs for Functional Studies
Brooke L. Fridley,Ed Iversen,Ya-Yu Tsai,Gregory D. Jenkins,Ellen L. Goode,Thomas A. Sellers
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0020764
Abstract: One difficult question facing researchers is how to prioritize SNPs detected from genetic association studies for functional studies. Often a list of the top M SNPs is determined based on solely the p-value from an association analysis, where M is determined by financial/time constraints. For many studies of complex diseases, multiple analyses have been completed and integrating these multiple sets of results may be difficult. One may also wish to incorporate biological knowledge, such as whether the SNP is in the exon of a gene or a regulatory region, into the selection of markers to follow-up. In this manuscript, we propose a Bayesian latent variable model (BLVM) for incorporating “features” about a SNP to estimate a latent “quality score”, with SNPs prioritized based on the posterior probability distribution of the rankings of these quality scores. We illustrate the method using data from an ovarian cancer genome-wide association study (GWAS). In addition to the application of the BLVM to the ovarian GWAS, we applied the BLVM to simulated data which mimics the setting involving the prioritization of markers across multiple GWAS for related diseases/traits. The top ranked SNP by BLVM for the ovarian GWAS, ranked 2nd and 7th based on p-values from analyses of all invasive and invasive serous cases. The top SNP based on serous case analysis p-value (which ranked 197th for invasive case analysis), was ranked 8th based on the posterior probability of being in the top 5 markers (0.13). In summary, the application of the BLVM allows for the systematic integration of multiple SNP “features” for the prioritization of loci for fine-mapping or functional studies, taking into account the uncertainty in ranking.
Comparison of percent density from raw and processed full-field digital mammography data
Celine M Vachon, Erin EE Fowler, Gail Tiffenberg, Christopher G Scott, V Shane Pankratz, Thomas A Sellers, John J Heine
Breast Cancer Research , 2013, DOI: 10.1186/bcr3372
Abstract: A case-control study of 180 cases and 180 controls matched by age, postmenopausal hormone use, and screening history was conducted. Mammograms were acquired from a General Electric Senographe 2000D FFDM unit. Percent density (PD) was assessed for each FFDM representation using the operator-assisted Cumulus method. Reproducibility within image type (n = 80) was assessed using Lin's concordance correlation coefficient (rc). Correlation of PD between image representations (n = 360) was evaluated using Pearson's correlation coefficient (r) on the continuous measures and the weighted kappa statistic (κ) for quartiles. Conditional logistic regression was used to estimate odds ratios (ORs) for the PD and breast cancer associations for both image representations with 95% confidence intervals. The area under the receiver operating characteristic curve (AUC) was used to assess the discriminatory accuracy.Percent density from the two representations provided similar intra-reader reproducibility (rc= 0.92 for raw and rc= 0.87 for processed images) and was correlated (r = 0.82 and κ = 0.64). When controlling for body mass index, the associations of quartiles of PD with breast cancer and discriminatory accuracy were similar for the raw (OR: 1.0 (ref.), 2.6 (1.2 to 5.4), 3.1 (1.4 to 6.8), 4.7 (2.1 to 10.6); AUC = 0.63) and processed representations (OR: 1.0 (ref.), 2.2 (1.1 to 4.1), 2.2 (1.1 to 4.4), 3.1 (1.5 to 6.6); AUC = 0.64).Percent density measured with an operator-assisted method from raw and processed FFDM images is reproducible and correlated. Both percent density measures provide similar associations with breast cancer.Increased mammographic breast density is an established breast cancer risk factor [1-3]. Irrespective of the method of measurement, the majority of studies have found a three- to sixfold increased risk of breast cancer in the highest vs. lowest density categories [2]. The majority of these studies estimated density from digitized film mammograms. Currently
Mammographic density, breast cancer risk and risk prediction
Celine M Vachon, Carla H van Gils, Thomas A Sellers, Karthik Ghosh, Sandhya Pruthi, Kathleen R Brandt, V Shane Pankratz
Breast Cancer Research , 2007, DOI: 10.1186/bcr1829
Abstract: Variation in the radiographic appearance of the breast reflects differences in tissue composition [1]: darker regions indicate fat tissue and lighter regions represent dense tissue, primarily fibroglandular tissue consisting of the functional elements or parenchyma, and supporting elements or stroma [2]. The proportion of the lighter or dense regions on the mammogram, characterized as mammographic density (MD), has consistently been one of the strongest risk factors for breast cancer, with risk estimates that are three- to five-fold greater for women in the highest quartile of density than for women of similar age in the lowest quartile [3]. As increased MD is common in the population, with 26% to 32% of women in the general population having densities of 50% or greater (Table 1), 16% to 32% of breast cancers may be attributed to this trait [4,5], with an even larger estimated proportion among premenopausal women [6].The magnitude and consistency of the MD and breast cancer association place its importance as a breast cancer risk factor alongside age, the presence of atypia on a breast biopsy, or carrying a highly penetrant breast cancer susceptibility gene (for example, BRCA1 and BRCA2) [7], the latter two which are rare in the population and responsible for only a small proportion of breast cancer. However, until recently, MD has not been used in clinical risk prediction models or clinical decision making. The purpose of this review is to summarize the evidence and strength of MD as a risk factor, review the studies that have evaluated MD in risk prediction, and discuss the implications of incorporating this trait into clinical practice for improving breast cancer risk assessment.The association between MD and breast cancer has been investigated in more than 50 studies over the last three decades. These studies have varied in their approaches to the measurement of MD (reviewed in Table 2), study designs, and populations. The majority (n = 42) of these studies were
An Unexpected Congruence Modulo 5 for 4--Colored Generalized Frobenius Partitions
James A. Sellers
Mathematics , 2013,
Abstract: In his 1984 AMS Memoir, George Andrews defined the family of $k$--colored generalized Frobenius partition functions. These are denoted by $c\phi_k(n)$ where $k\geq 1$ is the number of colors in question. In that Memoir, Andrews proved (among many other things) that, for all $n\geq 0,$ $c\phi_2(5n+3) \equiv 0\pmod{5}.$ Soon after, many authors proved congruence properties for various $k$--colored generalized Frobenius partition functions, typically with a small number of colors. In 2011, Baruah and Sarmah proved a number of congruence properties for $c\phi_4$, all with moduli which are powers of 4. In this brief note, we add to the collection of congruences for $c\phi_4$ by proving this function satisfies an unexpected result modulo 5. The proof is elementary, relying on Baruah and Sarmah's results as well as work of Srinivasa Ramanujan.
Vacuum Preparation, Optimization of Cylinder Length and Postoperative Daily Inflation Reduces Complaints of Shortened Penile Length Following Implantation of Inflatable Penile Prosthesis  [PDF]
Tom Sellers, Martin Dineen, Emad A. Salem, Steven K. Wilson
Advances in Sexual Medicine (ASM) , 2013, DOI: 10.4236/asm.2013.31003
Abstract:

Introduction: The inflatable penile prosthesis (IPP) has been used to treat erectile dysfunction for 40 years. Loss of penile length following IPP remains the single biggest patient complaint. We describe a preoperative and postoperative patient preparation protocol to assist in setting realistic patient expectations and decreasing the complaint of reduced penile length. Materials & Methods: 750 Patients are instructed to use a vacuum erection device for 10 minutes each day for up to 2 months prior to IPP implant. After two months, maximization of cylinder length is accomplished regardless of IPP manufacturer. Cylinders are left partially inflated in the post-operative period and daily inflation for 3 months immediately upon patient tolerance. The average implanted cylinder length has increased dramatically with the preoperative vacuum usage when compared to the authors’ previous implantations and when compared to the national average of implanted cylinders obtained from one manufacturer. Results: Preoperative use of the vacuum device has allowed maximization of cylinder length. After the vacuum program, patients tend to experience less pain following implantation allowing earlier device instruction cycling and use. The average implanted cylinder length continued to increase annually for the first 5 years as the protocol evolved and seems to have remained stable for the last five years. Conclusions: Preoperative vacuum usage and postoperative capsule management has nearly eliminated patient complaints of reduced penile length. We believe this to be the result of larger size cylinders being implanted when compared to our previous implantations absent of the patient participation protocol.

Computational proofs of congruences for -colored Frobenius partitions
Dennis Eichhorn,James A. Sellers
International Journal of Mathematics and Mathematical Sciences , 2002, DOI: 10.1155/s0161171202007342
Abstract: In 1994, the following infinite family of congruences was conjectured for the partition function cΦ2(n) which counts the number of 2-colored Frobenius partitions of n: for all n≥0 and α≥1, cΦ2(5αn
Congruences for spin characters of the double covers of the symmetric and alternating groups
Rishi Nath,James A. Sellers
Mathematics , 2015,
Abstract: Let $p$ be an odd prime. The bar partitions with sign and $p$-bar-core partitions with sign respectively label the spin characters and $p$-defect zero spin characters of the double cover of the symmetric group, and by restriction, those of the alternating group. The generating functions for these objects have been determined by J. Olsson. We study these functions from an arithmetic perspective, using classical analytic tools and elementary generating function manipulation to obtain many Ramanujan-like congruences.
A combinatorial proof of a relationship between maximal $(2k-1,2k+1)$ and $(2k-1,2k,2k+1)$-cores
Rishi Nath,James A. Sellers
Mathematics , 2015,
Abstract: Integer partitions which are simultaneously $t$--cores for distinct values of $t$ have attracted significant interest in recent years. When $s$ and $t$ are relatively prime, Olsson and Stanton have determined the size of the maximal $(s,t)$-core $\kappa_{s,t}$. When $k\geq 2$, a conjecture of Amdeberhan on the maximal $(2k-1,2k,2k+1)$-core $\kappa_{2k-1,2k,2k+1}$ has also recently been verified by numerous authors. In this work, we analyze the relationship between maximal $(2k-1,2k+1)$-cores and maximal $(2k-1,2k,2k+1)$-cores. In previous work, the first author noted that, for all $k\geq 1,$ $$ \vert \, \kappa_{2k-1,2k+1}\, \vert = 4\vert \, \kappa_{2k-1,2k,2k+1}\, \vert $$ and requested a combinatorial interpretation of this unexpected identity. Here, using the theory of abaci, partition dissection, and elementary results relating triangular numbers and squares, we provide such a combinatorial proof.
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