Search

Mantle cell lymphoma (MCL) is a biologically and clinically heterogeneous disease, emphasizing the need for prognostic biomarkers. In this study we aimed at comparing the prognostic value of two RNA-based risk scores, circSCORE and MCL35, in 149 patients from the MCL2 (ISRCTN87866680) and MCL3 (NCT00514475) patient cohorts. Both risk scores provided significant stratification of high versus low risk for progression free survival (PFS) and overall survival (OS). The circSCORE retained significant prognostic value in adjusted multivariable Cox regressions for PFS, but not for OS. Furthermore, circSCORE added significant prognostic value to MIPI in the pooled cohort (MCL2 and MCL3) for PFS and OS, and for PFS in MCL3 alone, outperforming Ki67 and MCL35. We suggest a new, combined MIPI-circSCORE with improved prognostic value, and with potential for future clinical implementation, if validated in a larger, independent cohort. [ABSTRACT FROM AUTHOR]

Ibrutinib has dramatically changed the treatment landscape for chronic lymphocytic leukemia (CLL) since its availability in British Columbia (BC), Canada in 2014. We analyzed patterns of use and real-world survival outcomes in 370 patients who received ibrutinib for first-line (1 L, n = 35) and relapsed/refractory (R/R, n = 335) CLL between 2014–2018 in BC. Dose reductions and interruptions were frequent in 32% and 27%, respectively. With a median follow-up of 27.6 months, 35% of patients discontinued ibrutinib, primarily for adverse events (AEs) rather than progressive disease. Over the course of treatment, 87% of patients experienced at least one adverse event. The 2-year overall survival (OS) and event-free survival (EFS) were excellent at 83.9% and 76.1%, respectively, with medians not reached. However, patients who discontinued ibrutinib had a median OS of 32.5 months and median EFS of only 3.8 months from time of discontinuation, highlighting the need to minimize toxicity in the real-world. [ABSTRACT FROM AUTHOR]

In that study, patients who started treatment more than 8 weeks after diagnosis were older and had other identifiable reasons for treatment delays (ex. comorbidities) that may have contributed to the association between treatment delay and OS. "Refusers" were further refined to patients who had at least a 16-week interval between pathologic diagnosis and treatment, and after chart review had declined to undergo the recommended treatment. With extended follow up, 13% of patients in the refuser cohort (2 of 15 refusers) died from cHL specifically, compared to 4% of patients in the control cohort (2 of 47 controls) though this did not reach statistical significance ( I p i = 0.185, Figure 1(c)). Fortunately, treatment refusal is uncommon, as only 17 (0.6%) patients out of a total of 2640 diagnosed with cHL over 20 years had documented initial treatment refusal. [Extracted from the article]

Up-regulation of BCL2 in cases of diffuse large B-cell lymphoma (DLBCL) can confer treatment resistance. Quantitative immunofluorescence (QIF) histology allows objective quantification of protein-based biomarkers. We investigated the utility of QIF for evaluating BCL2 as a biomarker in DLBCL by quantifying BCL2 selectively in CD20-expressing lymphoma cells in biopsy samples from 116 cases of DLBCL in two cohorts one of which consisted of relapsed/refractory cases from a clinical trial. BCL2 protein by QIF correlated with BCL2 mRNA abundance and was associated with both translocation and copy number gain of the BCL2 gene. Elevated BCL2 protein expression by QIF, but not immunohistochemistry or mRNA quantification, was associated with inferior overall and relapse-free survival in the relapsed/refractory cohort. QIF is an effective means of quantifying BCL2 protein objectively in routine cancer biopsy specimens and shows promise for identifying relapsed/refractory DLBCL patients at risk of inferior outcomes after salvage therapy. [ABSTRACT FROM AUTHOR]

Non-ductile reinforced concrete frames have seismic vulnerabilities due to inadequate reinforcing details. Adequately characterizing the performance of these details is critical to the development of analytical models. This study presents a methodology to simulate the response of such frames with and without fiber-reinforced polymer column jackets. The bond-slip effects between reinforcing bars and surrounding concrete, observed in column lap-splice and beam–column joints, are modeled with one-dimensional slide line models in LS-DYNA. The model is defined from failure modes and bonding conditions observed in full-scale dynamic tests and can predict story displacements, inter-story drifts, and damage mechanisms. [ABSTRACT FROM AUTHOR]

In this study, we analyzed the evolution of the prognosis of primary central nervous system lymphoma (PCNSL) patients as they reach selected progression-free survival (PFS) milestones after high-dose methotrexate (HD-MTX)-based therapy. In total, 258 and 146 patients were included from Denmark and British Columbia, respectively. All patients were diagnosed during 2000–2017. The 5-year PFS was 27% (95% CI 23; 32); however, for patients reaching 5 years of PFS, this increased to 71% (95% CI 57; 86). Within the first 5 years after diagnosis, patients lost 2.0 years (95% CI 1.8; 2.2) when compared to a similar background population. This reduced to 0.5 years (95% CI 0.2; 0.9) for patients reaching 5 years of PFS. Treatment with rituximab was associated with improved outcomes. The prognosis of patients with PCNSL treated with HD-MTX-based regimens in this cohort is poor, although it improves as patients survive without progression/relapse. However, survival does not conclusively normalize to that of a similar background population. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) accounts for about 20% of all non-Hodgkin lymphoma (NHL) and is the most common indolent form. More importantly, the leading cause of death among patients with FL remains the disease itself, particularly among the 20% that will experience an early event or those whose disease will eventually transform [[2]], making these events the real unmet need in FL. With the addition of 224 cases of de novo HT (8%, excluded from predictive marker analysis), Madsen et al. [[13]] report here a total of 521 HT, representing the largest cohort of HT in the literature. While presenting a similar PFS, patients with a I de novo i HT had a significantly shorter OS than non-transformed patients (68 versus 82% at 5 years, even though non-re-biopsied but clinically transformed patients were, by definition, included in the latest group), highlighting slight distinctions from pre-R-era data [[4]]. [Extracted from the article]

In this article, we apply Peter Berger's theory of religion as a social construct to learn how The Church of Jesus Christ of Latter-day Saints (the Mormon Church) advances a heteronormative view of family relationships in the United States using a document titled The Family: A Proclamation to the World. Furthermore, applying cultural studies theory, we examine how believing Mormons negotiate the tension that arises when their secular values compete with those expressed by Church leaders. We argue that, although the Proclamation addresses a number of issues, the Church offers a closed text that emphasizes war narratives in which same-sex marriage is portrayed as a threat to LDS identity and the heteronormative family. This closed text is further legitimized by emphasis on the authority of Church leaders as oracles of God. The study participants largely accept the dominant narrative, and those who reject it, do so with some trepidation. [ABSTRACT FROM AUTHOR]

University ranking is a popular yet controversial endeavor. Most rankings are based on both public data, such as student test scores and retention rates, and proprietary data, such as school reputation as perceived by high school counselors and academic peers. The weights applied to these characteristics to compute the rankings are often determined in a subjective fashion. Of significant importance in the academic field, the Carnegie Classification was developed by the Carnegie Foundation for the Advancement of Teaching. It has been updated approximately every 5 years since 1973, most recently in February 2016. Based on bivariate scores, Carnegie assigns one of three classes (R1/R2/R3) to doctorate-granting universities according to their level of research activity. The Carnegie methodology uses only publicly available data and determines weights via principal component analysis. In this article, we review Carnegie's stated goals and the extent to which their methodology achieves those goals. In particular, we examine Carnegie's separation of aggregate and per capita (per tenured/tenure-track faculty member) variables and its use of two separate principal component analyses on each; the resulting bivariate scores are very highly correlated. We propose and evaluate two alternatives and provide a graphical tool for evaluating and comparing the three scenarios. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on the use of Lymph2Cx assay, digital gene expression, to diffuse large B-cell lymphoma (DLBCL) cell-of-origin (COO) classification.

In recent decades, there has been growing interest in learning how museums reinforce and challenge popular culture. Scholars are beginning to examine the manner in which the use of objects, visual display, and media-saturated discourse in museums empowers their message. This study adds to this literature by examining the role of media, religion and the subjectivities of religious patrons in meaning-making practices at the Creation Museum in Kentucky. We learn that the museum's narrative resonates with the public memory regarding the role of traditional museums and a biblio-centric view of the world. This increases the veracity of its religious message. [ABSTRACT FROM AUTHOR]

We investigate a robust penalized logistic regression algorithm based on a minimum distance criterion. Influential outliers are often associated with the explosion of parameter vector estimates, but in the context of standard logistic regression, the bias due to outliers always causes the parameter vector to implode, that is, shrink toward the zero vector. Thus, using LASSO-like penalties to perform variable selection in the presence of outliers can result in missed detections of relevant covariates. We show that by choosing a minimum distance criterion together with an elastic net penalty, we can simultaneously find a parsimonious model and avoid estimation implosion even in the presence of many outliers in the important smallnlargepsituation. Minimizing the penalized minimum distance criterion is a challenging problem due to its nonconvexity. To meet the challenge, we develop a simple and efficient MM (majorization–minimization) algorithm that can be adapted gracefully to the smallnlargepcontext. Performance of our algorithm is evaluated on simulated and real datasets. This article has supplementary materials available online. [ABSTRACT FROM AUTHOR]

Frequency tables are often constructed on intervals of irregular width. When plotted as bar charts, the underlying true density information may be quite distorted. The majority of introductory statistics texts recommend tabulating data into intervals of equal width, but seldom caution the consequences of failing to do so. An occasional introductory text correctly emphasizes that area rather than frequency should be plotted. Nevertheless, the correctly scaled density figure is often visually less informative than one might expect, with wide bins at constant height. In many cases, the rightmost bin interval has no well-defined endpoint, making its depiction somewhat arbitrary. In this note, we introduce a regular histogram approximation that matches the frequencies and also minimizes a roughness criterion for visual and exploratory appeal. The resulting estimate can reveal the density structure much more clearly. We also formulate an alternative criterion that explicitly takes account of the uncertainty in the bin frequencies. [ABSTRACT FROM AUTHOR]

This study applies a textual analysis of the marketing efforts and on-site representations of history at the Church of Jesus Christ of Latter-day Saints' Temple Square in Salt Lake City, Utah. Guided by the literature regarding museums as discursive constructs that at times sacrifice historic accuracy in order to appeal to visitors' expectations, this study demonstrates the role of pioneer mythology and the discursive construct of "museumness" at Temple Square as elements that contribute to the success of the square as a tourist destination. [ABSTRACT FROM AUTHOR]

This research is premised on Stuart Hall's encoding/decoding model and on Berger's concept that religiosity is socially constructed. However, unlike the early Birmingham studies' emphasis on socioeconomic status as a "cultural code" through which audience members would decode media texts, this study examines the readings of television texts from the perspective of audience members who are, because of their religious practices, ideologically situated to the right of much that is offered on television. The findings in this case are consistent with Hall's notion that individuals bring contradictory and conflicting discourse into their readings of media texts. [ABSTRACT FROM AUTHOR]

Cyberspace constitutes a place where people can build personal relationships and share norms or expectations that are meaningful and real for them (Paccagnella, 2002). Rooted in the social constructivist tradition (Berger & Luckmann, 1966), this study examines the role of religiosity and the Internet in the discursive strategies of single Mormons seeking relationships on the Web. The findings add to the literature addressing both virtual and religious communities by demonstrating how a virtual community is built and sustained by the religious discourse of its members. [ABSTRACT FROM AUTHOR]

Presents a study which calculated measure of similarity between pairs of densities and illustrated its use in recursively collapsing components. Use of mixture models in modeling complex densities; Equation used in similarity measure for densities; Simplification of a mixture model based on an average shifted histogram density estimate.

Presents a study which investigated the use of integrated square error (ISE) as a theoretical and practical estimation tool for a variety of parametric statistical models. Estimation criteria in which parametric and nonparametric algorithms are based; Derivation of the nonparametric least squares cross-validation algorithm; Demonstration of the consistency and asymptotic normality of the ISE parameters.

Theoretical and practical aspects of the sample-point adaptive positive kernel density estimator are examined A closed-form expression for the mean integrated squared error is obtained through the device of preprocessing the data by binning. With this expression, the exact behavior of the optimally adaptive smoothing parameter function is studied for the first time. The approach differs from most earlier techniques in that bias of the adaptive estimator remains O(h²) and is not "improved" to the rate O(h²). A practical algorithm is constructed using a modification of least squares cross-validation. Simulated and real examples are presented, including comparisons with a fixed bandwidth estimator and a fully automatic version of Abramson's adaptive estimator. The results are very promising. [ABSTRACT FROM AUTHOR]

Proposes a new hybrid method that combines nonparametric regression with the L1 norm. Problem of estimating the regression function; Limitations of the robust procedure and the nonparametric regression models; Advantages of the new hybrid method.

Nonparametric density estimation requires the specification of smoothing parameters. The demands of statistical objectivity make it highly desirable to base the choice on properties of the data set. In this article we introduce some biased cross-validation criteria for selection of smoothing parameters for kernel and histogram density estimators, closely related to one investigated in Scott and Factor (1981). These criteria are obtained by estimating L[sub 2] norms of derivatives of the unknown density and provide slightly biased estimates of the average squared L[sub 2] error or mean integrated squared error. These criteria are roughly the analog of Wahba's (1981) generalized cross-validation procedure for orthogonal series density estimators. We present the relationship of the biased cross-validation procedure to the least squares cross-validation procedure, which provides unbiased estimates of the mean integrated squared error. Both methods are shown to be based on U statistics. We compare the two methods by theoretical calculation of the noise in the cross-validation functions and corresponding cross-validated smoothing parameters, by Monte Carlo simulation, and by example. Surprisingly large gains in asymptotic efficiency are observed when biased cross-validation is compared with unbiased cross-validation if the underlying density is sufficiently smooth. The theoretical results explain some of the small sample behavior of cross-validation functions: we show that cross-validation algorithms can be unreliable for sample sizes that are "too small." To aid the practitioner in the use of these appealing automatic cross-validation algorithms and to help facilitate evaluation of future algorithms, we must address some oftentimes controversial issues in density estimation: squared loss, the integrated squared error and mean integrated squared... [ABSTRACT FROM AUTHOR]

In this article I investigate the theoretical properties and applications of the frequency polygon, which is constructed by connecting with straight lines the mid-bin values of a histogram. For estimating an unknown probability density function using a random sample, the frequency polygon is shown to dominate the histogram with respect to the criterion of integrated mean squared error, achieving the same rate of convergence to zero of the integrated mean squared error as non-negative kernel estimators. Data-based algorithms for constructing frequency polygons are discussed and illustrated. One is based on a histogram with bin width equal to 2.15sn[sup -1/5], where s is an estimate of the standard deviation from a sample of size n. Another approach is based on the method of generalized cross-validation. The bivariate frequency polygon is also investigated. Comparisons are made between the frequency polygon and other density estimators. Examples with data in one and two dimensions are presented. [ABSTRACT FROM AUTHOR]

The optimal histogram for a sample of size n from a density defined on the entire real line requires at least (2n)[sup 1/3] bins, under mild smoothness conditions. Similar bounds exist for the frequency polygon and kernel estimators. Values near these bounds give nearly optimal results for a variety of smooth densities, providing good, quick density estimates. [ABSTRACT FROM AUTHOR]

Although the theoretical properties of modern nonparametric probability density estimators have been studied for 25 years, there remains the practical problem of how to specify the amount of bias or smoothing in a density estimate based on a random sample. In this paper we review and evaluate three recently developed data-based algorithms that completely specify a density estimate from a random sample. Using Monte Carlo techniques, we compare the statistical accuracy of these algorithms as measured by the integrated mean squared error. In addition, we examine the sensitivity of these algorithms to outliers and estimate computer time requirements. One conclusion we draw is that the statistical accuracy of these data-based algorithms seems comparable to levels predicted by theoretical models. [ABSTRACT FROM AUTHOR]

The article discusses the permanent location of the National Collection of Fine Arts in the renovated Old Patent Office Building in downtown Washington. It also discusses a variety of specialized training and study opportunities provided by the National Collection via internships and research grants offered by the Smithsonian's Office of Education and Training. It suggests that various programs of the National Collection provide informational, educational and research facilities by promoting travel assistance and government art activities such as the Smithsonian Traveling Exhibition Service and the White House rotating exhibition.

Given the relatively slow convergence of cross-validation methods, it is very helpful to compare several different cross-validation algorithms. When these agree authors are satisfied. When they do not, authors investigate further. Methods preferred by authors are all highly correlated. Development of a complementary biased cross-validation procedure in regression may be as useful as in density estimation. Any difficulties with cross-validation do not necessarily imply that an excellent nonparametric regression curve does not exist. Authors have provided a deeper understanding of the theory and practice of databased methods in non-parametric regression. Although the error criterion introduced in regression is average squared error, most theoretical work has examined the mean average squared error. In density-estimation simulations, authors found the improvement was only occasionally large and was small relative to the range of observed integrated squared errors. Perhaps unexpectedly, a clear preference is not always made with such large data sets, but the author believes that many interesting and practical questions remain about applying cross-validation procedures.

Introduces a series of articles published in the volume 12, number 4, December 2003 issue of the "Journal of Computational and Graphical Statistics."

Statisticians like Good and Gaskins have given to bump-hunters an inventive approach that uses the special structure of their maximum penalized-likelihood, MPL procedure. This article demonstrates the usefulness of nonparametric density-estimation techniques for unearthing features such as modes in the body of the data without concern for possible tail pathologies. With medical data the estimation and comparison of modes has proved more revealing than simpler tests. For example, the discovery of bimodal bivariate density functions in lipid data has led to clarification of the roles of certain cardiovascular risk factors. Investigators interested in the statistical significance of modes should also find Good and Gaskins's paper useful. The important algorithms presented in this paper deal with optimization of the smoothness or variance-bias trade-off of the density estimate and with removal of potential bumps by surgery.

Comments on the article "Transformations in Density Estimation," by M.P. Wand, J.S. Warron and D. Ruppert, which focuses on kernel density estimation for one dimensional data. Improvement in the informal use of data transformation for density estimation; Importance of using transformations for multivariate density estimation; Theoretical investigation of the asymptotic global properties of adaptive density estimators.