Simultaneous inference based on rank statistics in linear models

Mansouri, Hossein

doi:10.1080/00949655.2013.836292

Cited by 7 publications

(9 citation statements)

References 15 publications

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“…S5). To determine the impact on activation and polarization of TAMs, expression of iNOS (typical of classically activated inflammatory M1 macrophages) and Arg1 (typical of alternatively-activated anti-inflammatory M2 macrophages) [24,34], were assessed by flow cytometry. We found that PLN, but not PLN-alen, increased numbers of a mixed M1/M2 TAM population, characterized by production of both iNOS and Arg1, as compared to vehicle control ( P = 0.045) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Splenic myeloid cells (macrophages, resident monocytes, inflammatory monocytes, granulocytes, and dendritic cells) and tumor myeloid cells (TAM and MDSC) were identified and enumerated. Expression of iNOS and Arg1 was used to define M1 (iNOS + Arg1 − ), M2 (iNOS − Arg1 + ), and mixed M1/M2 (iNOS + Arg1 + ) phenotypes [24,34]. T-cells (TCRβ + CD8b + or TCRβ + CD4 + ) were enumerated in a similar manner.…”

Section: Methodsmentioning

confidence: 99%

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Liposome-induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome-encapsulated alendronate

Rajan

Sabnani

Mavinkurve

et al. 2018

Journal of Controlled Release

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Liposomal nanoparticles are the most commonly used drug nano-delivery platforms. However, recent reports show that certain pegylated liposomal nanoparticles (PLNs) and polymeric nanoparticles have the potential to enhance tumor growth and inhibit antitumor immunity in murine cancer models. We sought herein to identify the mechanisms and determine whether PLN-associated immunosuppression and tumor growth can be reversed using alendronate, an immune modulatory drug. By conducting in vivo and ex vivo experiments with the immunocompetent TC-1 murine tumor model, we found that macrophages were the primary cells that internalized PLN in the tumor microenvironment and that PLN-induced tumor growth was dependent on macrophages. Treatment with PLN increased immunosuppression as evidenced by increased expression of arginase-1 in CD11b+Gr1+ cells, diminished M1 functionality in macrophages, and globally suppressed T-cell cytokine production. Encapsulating alendronate in PLN reversed these effects on myeloid cells and shifted the profile of multi-cytokine producing T-cells towards an IFNγ+ perforin+ response, suggesting increased cytotoxic functionality. Importantly, we also found that PLN-encapsulated alendronate (PLN-alen), but not free alendronate, abrogated PLN-induced tumor growth and increased progression-free survival. In summary, we have identified a novel mechanism of PLN-induced tumor growth through macrophage polarization and immunosuppression that can be targeted and inactivated to improve the anticancer efficacy of PLN-delivered drugs. Importantly, we also determined that PLN-alen not only reversed protumoral effects of the PLN carrier, but also had moderate antitumor activity. Our findings strongly support the inclusion of immune-responsive tumor models and in-depth immune functional studies in the preclinical drug development paradigm for cancer nanomedicines, and the further development of chemo-immunotherapy strategies to co-deliver alendronate and chemotherapy for the treatment of cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Liposome-induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome-encapsulated alendronate

Rajan

Sabnani

Mavinkurve

et al. 2018

Journal of Controlled Release

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“…Indeed, some ART contrast methods have been presented in the literature [1,4,[29][30][31], but the authors did not address how or whether their methods can be used across multiple factors, showing only examples of single-factor contrasts even in the presence of signifcant interaction efects. Simulation studies analyzing the efectiveness of ART contrasts also only included data with a single factor [1,4,34].…”

Section: Multifactor Contrastsmentioning

confidence: 99%

An Aligned Rank Transform Procedure for Multifactor Contrast Tests

Elkin

Kay

Higgins

et al. 2021

The 34th Annual ACM Symposium on User Interface Software and Technology

325

126

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Data from multifactor HCI experiments often violates the assumptions of parametric tests (i.e., nonconforming data). The Aligned Rank Transform (ART) has become a popular nonparametric analysis in HCI that can fnd main and interaction efects in nonconforming data, but leads to incorrect results when used to conduct post hoc contrast tests. We created a new algorithm called ART-C for conducting contrast tests within the ART paradigm and validated it on 72,000 synthetic data sets. Our results indicate that ART-C does not infate Type I error rates, unlike contrasts based on ART, and that ART-C has more statistical power than a t-test, Mann-Whitney U test, Wilcoxon signed-rank test, and ART. We also extended an open-source tool called ARTool with our ART-C algorithm for both Windows and R. Our validation had some limitations (e.g., only six distribution types, no mixed factorial designs, no random slopes), and data drawn from Cauchy distributions should not be analyzed with ART-C.

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“…Although pairwise comparisons based on overall ranking are extended to factorial designs and general linear models based on the aligned rank transformation methodology, Mansouri [12], the methods based on separate rankings are limited to one-way layouts and randomized complete blocks, see [7]. It is the aims of this investigation to extend the method of pairwise comparisons based on separate rankings to a model that includes the factorial models and analysis of covariance as a special case.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Rank Tests in Analysis of Covariance Based on Pairwise Ranking

Mansouri

Zhang²

2018

Preprint

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Nonparametric tests provide robust and powerful alternatives to the corresponding least squares methods. There are two approaches to nonparametric pairwise comparisons of treatment effects, the method based on pairwise rankings and the method based on overall ranking. The former is generally recommended in the literature because of its strong control of familywise error rate. However, this method is developed only for one-way layouts and randomized complete blocks. By combining the method of aligned ranks and pairwise ranking, we extend the Steel-Dwass pairwise comparisons to the analysis of covariance and factorial models for both one-sided and two-sided comparisons as well as testing for treatment versus control. Unlike the traditional twosample standardization of test statistics, we propose a weighted estimate of the scale parameter for ranks and show through simulation that it has superior small sample performance by controlling the familywise error rate at nominal level. This method provides an improvement for large sample approximation of Steel-Dwass method for one-way layouts. The marginal and joint asymptotic distributions are derived and power comparisons are made with the method of aligned rank transformation and the least squares method.

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Simultaneous inference based on rank statistics in linear models

Cited by 7 publications

References 15 publications

Liposome-induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome-encapsulated alendronate

Liposome-induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome-encapsulated alendronate

An Aligned Rank Transform Procedure for Multifactor Contrast Tests

Simultaneous Rank Tests in Analysis of Covariance Based on Pairwise Ranking

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