Biomedical subjects

Elizabeth H Slate

Publications and source records attributed to Elizabeth H Slate.

9 recordsLinked to original sources

PubMed2006

A multivariate prediction model for microarray cross-hybridization.

BACKGROUND: Expression microarray analysis is one of the most popular molecular diagnostic techniques in the post-genomic era. However, this technique faces the fundamental problem of potential cross-hybridization. This is a pervasive problem for both oligonucleotide and cDNA microarrays; it is considered particularly problematic for the latter. No comprehensive multivariate predictive modeling has been performed to understand how multiple variables contribute to (cross-) hybridization. RESULTS: We propose a systematic search strategy using multiple multivariate models [multiple linear regressions, regression trees, and artificial neural network analyses (ANNs)] to select an effective set of predictors for hybridization. We validate this approach on a set of DNA microarrays with cytochrome p450 family genes. The performance of our multiple multivariate models is compared with that of a recently proposed third-order polynomial regression method that uses percent identity as the sole predictor. All multivariate models agree that the 'most contiguous base pairs between probe and target sequences,' rather than percent identity, is the best univariate predictor. The predictive power is improved by inclusion of additional nonlinear effects, in particular target GC content, when regression trees or ANNs are used. CONCLUSION: A systematic multivariate approach is provided to assess the importance of multiple sequence features for hybridization and of relationships among these features. This approach can easily be applied to larger datasets. This will allow future developments of generalized hybridization models that will be able to correct for false-positive cross-hybridization signals in expression experiments.

Algorithms↗

PubMed2006

Study design for calibration of clinical examiners measuring periodontal parameters.

BACKGROUND: We present an approach to examiner calibration study design where the number of calibration subjects is based on a specified margin of error (half-width of the 95% confidence interval [CI]) of the percentage of agreement (exact and within 1 mm) for both intra- and interexaminer reliability assessments. METHODS: An experienced standard examiner (S) trained three dental hygienists (A, B, and C) in correct procedures for obtaining a variety of periodontal measures. Duplicate measurements of probing depth (PD [mm]) and the free gingival margin to the cemento-enamel junction (CEJ-GM [mm]) were obtained in a pilot study to design a formal examiner calibration study, where sample sizes were adjusted for the effects of within-subject clustering of binary indices of agreement. RESULTS: Within-subject clustering of agreement indices resulted in an approximate four-fold increase in the variance of the estimates of percentage of agreement with the standard. PD and CEJ-GM percentage of exact agreement measurements (95% CI) for each examiner-standard pair, respectively, were as follows: AS=55% (48%, 61%) and 70% (62%, 78%); BS=52% (45%, 59%) and 73% (63%, 82%); and CS=55% (50%, 61%) and 72% (65%, 79%). The corresponding 95% CIs unadjusted for the effects of clustering underestimated the margin of error associated with the estimates of exact agreement by as much as 57% for PD and 68% for CEJ-GM. CONCLUSION: Failure to account for dependence among site-level agreement indices results in a false sense of precision in the resulting reliability estimates and can lead to faulty inference.

Adolescent↗

PubMed2005

Modelling intervention effects after cancer relapses.

This article addresses the problem of incorporating information regarding the effects of treatments or interventions into models for repeated cancer relapses. In contrast to many existing models, our approach permits the impact of interventions to differ after each relapse. We adopt the general model for recurrent events proposed by Peña and Hollander, in which the effect of interventions is represented by an effective age process acting on the baseline hazard rate function. To accommodate the situation of cancer relapse, we propose an effective age function that encodes three possible therapeutic responses: complete remission, partial remission, and null response. The proposed model also incorporates the effect of covariates, the impact of previous relapses, and heterogeneity among individuals. We use our model to analyse the times to relapse for 63 patients with a particular subtype of indolent lymphoma and compare the results to those obtained using existing methods.

Female↗

PubMed2005

Sodium lactate increases LPS-stimulated MMP and cytokine expression in U937 histiocytes by enhancing AP-1 and NF-kappaB transcriptional activities.

The plasma lactate concentration in patients with obesity and type 2 diabetes is often higher than that in nondiabetic individuals. Although it is known that increased lactate concentration is an independent risk factor for developing type 2 diabetes, the underlying mechanisms are not well understood. Because inflammation plays an important role in the development of type 2 diabetes, we postulated that increased lactate level might contribute to the pathogenesis of type 2 diabetes by enhancing inflammation. In the present study, we demonstrated that preexposure of U937 macrophage-like cells to sodium lactate increased LPS-stimulated matrix metalloproteinase (MMP)-1, IL-1beta, and IL-6 secretion. Augmentation of LPS-stimulated MMP-1 secretion was diminished when sodium lactate was replaced by lactic acid that reduced pH in the culture medium. Furthermore, quantitative real-time PCR indicated that the increased secretion of MMP-1, IL-1beta, and IL-6 was due to increased mRNA expression. To explore the underlying signaling mechanism, blocking studies using specific inhibitors for NF-kappaB and MAPK cascades were performed. Results showed that blocking of either NF-kappaB or MAPK pathways led to the inhibition of MMP-1, IL-1beta, and IL-6 expression stimulated by sodium lactate, LPS, or both. Finally, electrophoretic mobility shift assays showed a synergy between sodium lactate and LPS on AP-1 and NF-kappaB transcriptional activities. In conclusion, this study has demonstrated for the first time that sodium lactate and LPS exert synergistic effect on MMP and cytokine expression through NF-kappaB and MAPK pathways and revealed a novel mechanism potentially involved in the development of type 2 diabetes and its complications.

Cytokines↗

PubMed2004

Flap thickness accuracy: comparison of 6 microkeratome models.

PURPOSE: To determine the flap thickness accuracy of 6 microkeratome models and determine factors that might affect flap thickness. SETTING: Magill Research Center for Vision Correction, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: This multicenter prospective study involved 18 surgeons. Six microkeratomes were evaluated: AMO Amadeus, Bausch & Lomb Hansatome, Moria Carriazo-Barraquer, Moria M2, Nidek MK2000, and Alcon Summit Krumeich-Barraquer. Eyes of 1061 consecutive patients who had laser in situ keratomileusis were included. Age, sex, surgical order (first or second cut), keratometry (flattest, steepest, and mean), white-to-white measurement, laser used, plate thickness, head serial number, blade lot number, and occurrence of epithelial defects were recorded. Intraoperative pachymetry was obtained just before the microkeratome was placed on the eye. Residual bed pachymetry was measured after the microkeratome cut had been created and the flap lifted. The estimated flap thickness was determined by subtraction (ie, mean preoperative pachymetry measurement minus mean residual bed pachymetry). RESULTS: A total of 1634 eyes were reviewed. Sex distribution was 54.3% women and 45.7% men, and the mean age was 39.4 years +/- 10.6 (SD). In addition, 54.5% of the procedures were in first eyes and 45.5%, in second eyes. The mean preoperative pachymetry measurement was 547 +/- 34 microm. The mean keratometry was 43.6 +/- 1.6 diopters (D) in the flattest axis and 44.6 +/-1.5 D in the steepest axis. The mean white-to-white measurement was 11.7 +/- 0.4 mm. The mean flap thickness created by the devices varied between head designs, and microkeratome heads had significant differences (P<.05). Factors that explained 78.4% of the variability included microkeratome model, plate thickness, mean preoperative pachymetry, Kmin, surgery order, head serial number, blade lot number, and surgeon. Factors such as age, sex, Kmax, Kaverage, white to white, and laser had no significant correlation to flap thickness. CONCLUSIONS: The results demonstrated variability between the 6 microkeratome models. Device labeling did not necessarily represent the mean flap thickness obtained, nor was it uniform or consistent. Thinner corneas were associated with thinner flaps and thicker corneas with thicker flaps. In addition, first cuts were generally associated with thicker flaps when compared to second cuts in bilateral procedures.

Adult↗

PubMed2004

Combining longitudinal studies of PSA.

Prostate-specific antigen (PSA) is a biomarker commonly used to screen for prostate cancer. Several studies have examined PSA growth rates prior to prostate cancer diagnosis. However, the resulting estimates are highly variable. In this article we propose a non-linear Bayesian hierarchical model to combine longitudinal data on PSA growth from three different studies. Our model enables novel investigations into patterns of PSA growth that were previously impossible due to sample size limitations. The goals of our analysis are twofold: first, to characterize growth rates of PSA accounting for differences when combining data from different studies; second, to investigate the impact of clinical covariates such as advanced disease and unfavorable histology on PSA growth rates.

Adult↗

PubMed2003

Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial.

The Nutritional Prevention of Cancer Trial was a double-blind, randomized, placebo-controlled clinical trial designed to test whether selenium as selenized yeast (200 microg daily) could prevent nonmelanoma skin cancer among 1312 patients from the Eastern United States who had previously had this disease. Results from September 15, 1983, through December 31, 1993, showed no association between treatment and the incidence of basal and squamous cell carcinomas of the skin. This report summarizes the entire blinded treatment period, which ended on January 31, 1996. The association between treatment and time to first nonmelanoma skin cancer diagnosis and between treatment and time to multiple skin tumors overall and within subgroups, defined by baseline characteristics, was evaluated. Although results through the entire blinded period continued to show that selenium supplementation was not statistically significantly associated with the risk of basal cell carcinoma (hazard ratio [HR] = 1.09, 95% confidence interval [CI] = 0.94 to 1.26), selenium supplementation was associated with statistically significantly elevated risk of squamous cell carcinoma (HR = 1.25, 95% CI = 1.03 to 1.51) and of total nonmelanoma skin cancer (HR = 1.17, 95% CI = 1.02 to 1.34). Results from the Nutritional Prevention of Cancer Trial conducted among individuals at high risk of nonmelanoma skin cancer continue to demonstrate that selenium supplementation is ineffective at preventing basal cell carcinoma and that it increases the risk of squamous cell carcinoma and total nonmelanoma skin cancer.

Adult↗

PubMed2002

Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial.

The Nutritional Prevention of Cancer Trial was a randomized, clinical trial designed to evaluate the efficacy of selenium as selenized yeast (200 microg daily) in preventing the recurrence of nonmelanoma skin cancer among 1312 residents of the Eastern United States. Original secondary analyses through December 31, 1993 showed striking inverse associations between treatment and the incidence of total [hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.46-0.82], lung, prostate, and colorectal cancer and total cancer mortality. This report presents results through February 1, 1996, the end of blinded treatment. Effect modification by baseline characteristics is also evaluated. The effects of treatment overall and within subgroups of baseline age, gender, smoking status, and plasma selenium were examined using incidence rate ratios and Cox proportional hazards models. Selenium supplementation reduced total (HR = 0.75, 95% CI = 0.58-0.97) and prostate (HR = 0.48, 95% CI = 0.28-0.80) cancer incidence but was not significantly associated with lung (HR = 0.74, 95% CI = 0.44-1.24) and colorectal (HR = 0.46, 95% CI = 0.21-1.02) cancer incidence. The effects of treatment on other site-specific cancers are also described. The protective effect of selenium was confined to males (HR = 0.67, 95% CI = 0.50-0.89) and was most pronounced in former smokers. Participants with baseline plasma selenium concentrations in the lowest two tertiles (<121.6 ng/ml) experienced reductions in total cancer incidence, whereas those in the highest tertile showed an elevated incidence (HR = 1.20, 95% CI = 0.77-1.86). The Nutritional Prevention of Cancer trial continues to show a protective effect of selenium on cancer incidence, although not all site-specific cancers exhibited a reduction in incidence. This treatment effect was restricted to males and to those with lower baseline plasma selenium concentrations.

Age Distribution↗

PubMedDate not supplied

Evidence of nephropathy and peripheral neuropathy in US adults with undiagnosed diabetes.

PURPOSE: Nearly one third of diabetes cases in the United States is undiagnosed, with mounting evidence that complications accrue even before clinical diagnosis. We wanted to determine whether persons with undiagnosed diabetes have signs of nephropathy and peripheral neuropathy. METHODS: We examined the prevalence of positive screening tests for nephropathy and peripheral neuropathy in adults aged > or = 40 years with undiagnosed diabetes using secondary analysis of survey and examination data from the population-based United States National Health and Nutrition Examination Survey 1999-2002. We defined a positive screening test for nephropathy as a spot urine albumin-creatinine ratio > 30.0 mg/g, representing at least microalbuminuria. We defined > or = 1 insensate area on Semmes-Weinstein monofilament testing as a positive finding for neuropathy. Undiagnosed diabetes was defined as a combination of no history of diagnosed diabetes and a measured fasting glucose > or = 126 mg/dL. We used SUDAAN for chi2 and regression analyses. RESULTS: The prevalence of a positive test when screening for nephropathy among those with undiagnosed diabetes was 26.5% compared with 7.1% in those with no diabetes (chi2, P <.01). After adjusting for age and diagnosed or undiagnosed hypertension, the association of undiagnosed diabetes with nephropathy persisted (odds ratio = 2.35; 95% confidence interval, 1.38-4.01). For peripheral neuropathy, 21.5% with undiagnosed diabetes had positive screening tests compared with 10.1% with no diabetes (chi2, P <.01); however, this effect was not significant after adjustment for age. There was no significant difference in positive screening tests for nephropathy or neuropathy when comparing those with undiagnosed and diagnosed diabetes. CONCLUSIONS: A significant proportion of adults with undiagnosed diabetes have signs of nephropathy and peripheral neuropathy. These findings may influence policies about early screening for diabetes.

Adult↗