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Brenda MacGibbon

Publications and source records attributed to Brenda MacGibbon.

7 recordsLinked to original sources

Creating non-parametric bootstrap samples using Poisson frequencies.

This article describes how, in the high-level software packages used by non-statisticians, approximate non-parametric bootstrap samples can be created and analyzed without physically creating new data sets, or resorting to complex programming. The comparable performance of this shortcut method, which uses Poisson rather than multinomial frequencies for the numbers of copies of each observation, is demonstrated theoretically by evaluating the bootstrap variance in an example where the classic estimator of the sampling variance of the statistic of interest has a known closed form. For sample sizes of 50 or more, bootstrap standard errors obtained by this shortcut method exceeded those obtained by the standard version by less than 1%. The proposed method is also evaluated in two worked examples, involving statistics whose sampling distribution is more complex. The second of these is also used to illustrate when one can and cannot use non-parametric bootstrap samples.

Computational Biology↗

Fiberoptic ductoscopy findings in women with and without spontaneous nipple discharge.

BACKGROUND: Fiberoptic ductoscopy (FD), which allows direct visualization of the breast ductal lumen, is performed in women with and without spontaneous nipple discharge (SND). Previous reports suggested that cytologic evaluation of SND may be falsely interpreted as containing malignancy. The purpose of the current study, which was performed prospectively, was to determine whether ductoscopic findings were different in women with versus without SND, and to assess the implications of the differences in SND versus non-SND samples regarding the role of FD in assessing whether a woman has breast carcinoma. METHODS: Data were collected on the distance traveled by the ductoscope, visual observations, pathology, cytology, epithelial and foam cell quantity, and image analysis for ploidy, hypertetraploidy, and S-phase fraction. RESULTS: Of 100 FD specimens, 60 were from breasts without SND and 40 were from breasts with SND. Intraductal visual observations (P < or = 0.0002), pathologic findings in the resected specimen (P < or = 0.001), and quantity of epithelial cells (P=0.03) were influenced by the presence or absence of SND. Although one specimen from a benign breast was interpreted as cytologically malignant, every breast with both malignant cytology and aneuploidy contained cancer cells. A model incorporating cytology and SND was 92% sensitive and 60% specific in predicting which women had breast carcinoma. CONCLUSIONS: There were pronounced differences in FD samples from women with and without SND. FD biologic parameters can be chosen to optimize breast carcinoma predictive sensitivity and specificity. SND cytology can present a diagnostic problem, suggesting the need for histologic confirmation before the initiation of therapy.

Adult↗

Quantifying postural tremor in workers exposed to low levels of manganese.

The aim of this study was: (1) To determine the minimum number of characteristics necessary to discriminate between postural tremor recorded in control subjects (CO), in subjects exposed to manganese (MN), and in patients with Parkinson's disease (PD), and (2) to examine the continuum of changes between the three groups examined. Workers previously exposed to Mn (n = 10), patients with PD (n = 10), and control subjects (CO) (n = 11) underwent a clinical examination. Blood Mn was measured at the end of exposure time for the MN group and 12 months later at the beginning of the experiment for all groups. Postural tremor with visual feedback was recorded in the index finger with a laser system. Statistical criteria were used to reduce computed tremor characteristics to a minimal set of reliable discriminating variables. Two variables were retained namely corrected wobble (CW), describing the morphology of the tremor oscillations, and variability ratio (VR), describing proportional power of tremor. Both variables had an overall correct classification rate of 77.4%. Blood Mn levels at the time of the experiment were similar for all groups and had insignificant correlation with tremor variables. However, blood Mn levels in workers which were also measured at the end of exposure time (i.e., 12 months before) showed significant correlation (Spearman's rank coefficient) with both harmonic index (rho = 0.70, P = 0.03) and first maximum of the autocorrelation function (rho = 0.89, P = 0.001). We conclude that (1) the tremor of workers exposed to Mn could be adequately described with only two variables; (2) a continuum of changes between tremor recorded in control subjects, in subjects exposed to Mn and in patients with PD was observed, with the MN group always found in between the control (CO) and the PD groups; (3) while blood Mn levels in workers were back at control levels at the time of the experiment, the effect of Mn on postural tremor was still detected. Thus our method has the potential to detect the effect of Mn on tremor with only two variables even after Mn level in the blood is back to normal values.

Chemical Industry↗

Ductoscopic cytology and image analysis to detect breast carcinoma.

BACKGROUND: The goal of the prospective study was to determine whether 1) image analysis (IA; including DNA index [DI], S-phase fraction, and the presence or absence of aneuploidy or hypertetraploidy [HT]) of fiberoptic ductoscopy (FD) breast specimens was feasible, 2) IA findings from FD specimens predicted histopathologic evidence of disease, and 3) a combination of IA, cytology, and clinical factors provided complementary information in the diagnosis of breast carcinoma. METHODS: IA and cytologic evaluation were performed on 106 consecutively collected ductoscopic specimens from 88 subjects. RESULTS: IA was successful in 73 (71%) FD specimens. HT (P = 0.03) was related to intraductal visual observations. The proportion of atypical papillomas with aneuploidy was greater (P = 0.05) than in any other class. The HT index was higher in atypical papilloma (P = 0.02) and in breast carcinoma (P = 0.05) than with other diagnoses. The proportion of papilloma cases with HT was greater (P = 0.04) than benign papillomas. Malignant cytology was associated with a higher DI (P = 0.02) and a higher HT index (P = 0.001) than nonmalignant (benign or atypical) cytology. HT (P = 0.002) was less common with cytology containing few epithelial cells, and the HT index was higher with malignant versus nonmalignant FD cytology (P = 0.001). The percentage of cells containing HT was greater in FD specimens that were suspicious for malignancy (P = 0.006) than in those with benign cytology or mild atypia. Considering all samples and combining IA, cytologic, and visual findings in a stepwise linear discriminant analysis optimized the sensitivity (61%) and specificity (90%) of breast carcinoma prediction. Excluding spontaneous nipple discharge (SND) samples and adding epithelial cell quantity in samples improved the model (sensitivity, 85%; specificity, 80%). CONCLUSIONS: IA was feasible in FD specimens whenever adequate epithelial cells were present. IA and cytologic findings were associated. Adding IA results to cytology and visual findings and excluding samples with SND improved diagnostic sensitivity.

Aneuploidy↗

Blood manganese and alcohol consumption interact on mood states among manganese alloy production workers.

Long-term exposure to manganese (Mn) can induce neurotoxic effects including neuromotor, neurocognitive and neuropsychiatric effects, but there is a great interpersonal variability in the occurrence of these effects. It has recently been suggested that blood Mn (MnB) may interact with alcohol use disorders, accentuating neuropsychiatric symptoms. The objective of the present study was to explore a possible interaction between alcohol consumption and MnB on mood states, using an existing data set on Mn exposed workers. Respirable Mn exposure in the plant averaged 0.23mg/m(3) and was correlated with MnB. All participants for whom all data on MnB concentration and mood (assessed with the Profile of Mood States (POMS)) were available and who reported currently drinking alcohol were included in the analyses (n=74). Workers were grouped according to their MnB concentration (<10 and > or =10 microg/l) and alcohol consumption (<400 and > or =400g per week). Two-way ANOVAs were performed on each POMS scale and Mann-Whitney tests were used to assess group differences. Workers in the higher alcohol consumption group had higher scores on three POMS scales: tension, anger and fatigue. There was no difference for POMS scale scores between MnB subgroups. Dividing the group with respect to alcohol consumption and MnB showed that the group with high alcohol consumption and high MnB displayed the highest scores. In the lower MnB category, those in the higher alcohol consumption group did not have higher scores than the others. The interaction term for alcohol consumption and MnB concentration was statistically significant (P<0.05) for the depression, anger, fatigue and confusion POMS scales. There was a tendency for tension (P<0.06), and it was not significant for vigor. This study shows the first evidence of an interaction between MnB and alcohol consumption on mood states among Mn exposed workers and supports the results from a previous population-based study.

Adult↗

Studies of prognostic factors in end-stage renal disease: an epidemiological and statistical critique.

We reviewed prognostic studies for patients treated with renal replacement therapy by using an electronic database and bibliographic review for 1990 to 1998. Using the inclusion criteria of English language, adult patients, primary article, minimum 50 patients, primary focus on prognostic factors, and mortality outcome, 104 articles were identified. The 104 articles were reviewed for eight epidemiological and seven statistical criteria that addressed the scientific validity and interpretability of results. The following percentages of the 104 articles satisfied each of the eight epidemiological criteria: (1) a priori hypothesis, 6%; (2) zero time specified, 49%; (3) prognostic factors collected before zero time, 69%; (4) inception cohort, 59%; (5) control for treatment, 74%; (6) operational criteria, 82%; (7) missing variables reported, 12%; and (8) loss to follow-up reported, 42%. Summary analysis showed that 76% of studies satisfied four or fewer of the eight identified criteria. In the 77 articles (74%) that used the Cox proportional hazards model, the following percentages of articles met each of the seven statistical criteria: (1) proportional hazards verified, 26%; (2) censoring explained, 57%; (3) multivariate analysis performed, 91%; (4) significance levels given, 99%; (5) age adjusted, 95%; (6) diabetes adjusted, 66%; and (7) cardiac adjusted, 44%. Summary analysis found that 47% of the 77 studies satisfied four or fewer of the seven identified criteria. Superficially, results appear to show that when the Cox proportional hazards model was used, statistical analysis was better than the epidemiological design. However, studies we examined had serious defects in both epidemiological design and statistical analysis. The consequent validity of results for the quantification of prognostic factors is questionable.

Adult↗

Ductoscopic cytology to detect breast cancer.

PURPOSE: Fiberoptic ductoscopy allows direct visualization of the breast ductal lumen, providing a targeted approach to the diagnosis of intraductal disease. The purpose of this prospective study was to determine whether (1) endoscopic evaluation of the breast could be reliably performed, and (2) ductoscopic data (intraductal distance traveled, visual observations, epithelial and foam cell quantity, cytology) predict whether a woman has breast cancer. PATIENTS AND METHODS: Ductoscopic information was collected on intraductal distance traveled, visual observations, epithelial and foam cell quantity, and cytology. RESULTS: Ductoscopic samples were successfully collected in 106/108 attempts. The first six specimens collected were acellular. Of the 100 remaining ductoscopic specimens, 37 were from breasts with ductal carcinoma in situ or invasive breast cancer, 10 from breasts with precancerous lesions, 37 duct hyperplasia/papilloma, 11 histologically normal specimens, and five specimens from breasts that did not undergo subsequent surgical excision. The ability to travel intraductally > or = 10 cm was greater in women with hyperplasia and papilloma (with and without atypia) lesions. Intraductal lesions that were visually considered tumors were more often hyperplasia/papilloma and malignant than other lesions. Extrinsic duct occlusion was observed only in malignant lesions. Excluding learning curve samples, 67/100 (45% of normal, 68% of hyperplastic, 90% of precancerous, 82% of ductal carcinoma in situ, and 70% of invasive) fiberoptic ductoscopy specimens had adequate epithelial cells, and all duct cannulation attempts except two were successful. There was one false-positive cytologic result in a woman found to have a papilloma. Foam cell quantity was significantly related to epithelial cell quantity. CONCLUSION: Fiberoptic ductoscopy is feasible in the vast majority of subjects. Fiberoptic ductoscopy is a specific but not sufficiently sensitive method to be used alone to diagnose breast cancer. The presence of highly atypical epithelial cells in specimens from breasts containing papillomas is a pitfall of this method. Caution must be exercised to avoid a false-positive diagnosis in patients with spontaneous nipple discharge.

Breast↗