PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 15573413

An age-adjusted bootstrap-based Poly-k test.

Hojin Moon·Hongshik Ahn·Ralph L Kodell
View original source ↗Export metadata ↓

Abstract

The assumption of an asymptotic normal distribution of some test statistics may be invalid in certain dose-response trend tests. For instance, the survival-adjusted Cochran-Armitage test, known as the Poly-k test, is asymptotically standard normal under the null hypothesis. However, the asymptotic normality is not valid if there is a deviation from the tumour onset distribution that is assumed in this test or if the competing risks survival rates differ across groups. We develop an age-adjusted bootstrap-based method to assess the significance of assumed asymptotic normal tests for animal carcinogenicity data. The proposed method differs from conventional bootstrap methods in the aspect of preserving the mortality rate in each dose group under the null hypothesis of equal tumour incidence rates among the groups. We investigate an empirical distribution of the Poly-3 (P3) trend test statistic using the proposed age-adjusted bootstrap-based method and compare it with the P3 test statistic referenced to the assumed standard normal distribution. A simulation study is conducted to evaluate the robustness of these tests to various Weibull-family tumour onset distributions. The proposed method is applied to National Toxicology Program data sets to evaluate a dose-related trend of a test substance on the incidence of neoplasms.

Explore related subjects

Age FactorsAlgorithmsAnimalsBiometryCarcinogenicity TestsCarcinogensDose-Response Relationship, DrugFemaleFuransLiver Neoplasms, ExperimentalLung NeoplasmsMaleMiceModels, StatisticalMonte Carlo MethodRatsRats, Inbred F344Journal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Hojin Moon, Hongshik Ahn, Ralph L Kodell. 2005-04-30. An age-adjusted bootstrap-based Poly-k test.. https://doi.org/10.1002/sim.1967

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Mean deviation fluctuation in eyes with stable Humphrey 24-2 visual fields.

AIM: To describe the expected fluctuation in the mean deviation (MD) scores on a large, long-term series of stable visual field reports for particular grades of defect in order to give clinicians an aid to the correct diagnosis of glaucomatous progression. METHOD: Visual field reports of subjects with five reliable consecutive Humphrey 24-2 visual fields, recorded over a period of at least 3 years, were scored using the Advanced Glaucoma Intervention Study (AGIS) system. The AGIS scores of the first and last visual fields were required to be identical. RESULTS: A total of 202 eyes from 202 patients were used in the study, with a total of 1010 visual fields being used in the analysis. Visual fields with no defect (AGIS score 0) had a 99% confidence interval (CI) of 0.3 dB, mild defects 0.4 dB, moderate defects 0.8 dB, severe 1 dB, and 1.3 dB for end-stage defects when considering variation of MD scores. Using a one-way ANOVA incorporating all stages showed very little fluctuation throughout the series (P=0.96). The correlation between the CI and grade of field defect showed a good positive correlation (r=0.7, P=0.0003) indicating an increase in CI as field defects worsen. CONCLUSION: When considering a series of reliable visual fields in a stable eye, one should expect only very little fluctuation in the MD, indicating that an increase in the MD beyond that of the 99% CI described may suggest progression. The reliability indices of the visual field test should be regarded as a primary consideration when assessing visual fields.

Age Factors↗
PubMed2006

Effect of methylglyoxal modification and phosphorylation on the chaperone and anti-apoptotic properties of heat shock protein 27.

Heat shock protein 27 (Hsp27) is a stress-inducible protein in cells that functions as a molecular chaperone and also as an anti-apoptotic protein. Methylglyoxal (MGO) is a reactive dicarbonyl compound produced from cellular glycolytic intermediates that reacts non-enzymatically with proteins to form products such as argpyrimidine. We found considerable amount of Hsp27 in phosphorylated form (pHsp27) in human cataractous lenses. pHsp27 was the major argpyrimidine-modified protein in brunescent cataractous lenses. Modification by MGO enhanced the chaperone function of both pHsp27 and native Hsp27, but the effect on Hsp27 was at least three-times greater than on pHsp27. Phosphorylation of Hsp27 abolished its chaperone function. Transfer of Hsp27 using a cationic lipid inhibited staurosporine (SP)-induced apoptotic cell death by 53% in a human lens epithelial cell line (HLE B-3). MGO-modified Hsp27 had an even greater effect (62% inhibition). SP-induced reactive oxygen species in HLE-B3 cells was significantly lower in cells transferred with MGO-modified Hsp27 when compared to native Hsp27. In vitro incubation experiments showed that MGO-modified Hsp27 reduced the activity of caspase-9, and MGO-modified pHsp27 reduced activities of both caspase-9 and caspase-3. Based on these results, we propose that Hsp27 becomes a better anti-apoptotic protein after modification by MGO, which may be due to multiple mechanisms that include enhancement of chaperone function, reduction in oxidative stress, and inhibition of activity of caspases. Our results suggest that MGO modification and phosphorylation of Hsp27 may have important consequences for lens transparency and cataract development.

Age Factors↗
PubMed2006

Sun exposure and host phenotype as predictors of cutaneous melanoma associated with neval remnants or dermal elastosis.

Recent research suggests that cutaneous melanomas may arise through 2 distinct pathways, characterized by chronic sun exposure on one hand and nevus-prone phenotype of the host on the other. Two histological characteristics of melanoma consistent with these divergent origins are dermal elastosis in adjacent skin and neval remnants contiguous with the tumor, respectively. To further explore causal heterogeneity in melanoma, we compared sun exposure histories and phenotypic characteristics among a population-based sample of patients newly diagnosed with cutaneous melanoma with and without contiguous neval remnants or dermal elastosis. Tissue blocks were obtained for 141 patients: 53 with superficial spreading melanoma (SSM) of the back, 42 with SSM of head and neck (H & N), and 39 and 7 with lentigo maligna/lentigo maligna melanoma (LM/LMM) of the H & N and back, respectively. Melanomas of the H & N were less likely than those on back to have neval remnants (adjusted OR 0.6, 95% CI 0.3-1.4), but were significantly more likely to have dermal elastosis (adjusted OR 9.3, 95% CI 3.5-25). In site-specific analyses, we found that H & N melanomas with neval remnants were more likely than those without neval remnants to arise in people with more than 60 nevi (adjusted OR 2.1, 95% CI 0.3-14.3), but were less likely to arise in those with more than 20 actinic keratoses. Less marked associations were observed for melanomas of the back. High levels of sun exposure strongly predicted dermal elastosis for H & N melanomas (OR 22.5, 95% CI 2.1-245), but not for melanomas of the back (OR 2.1, 95% CI 0.4-11). We conclude that melanomas with different histologic characteristics have different risk factor profiles, particularly on the head and neck. These data accord with the hypothesis that melanomas arise through different causal pathways.

Age Factors↗