Differential Proteomics for Distinguishing Ischemic Stroke from Controls: a Pilot Study of the SpecTRA Project.

A diagnostic blood test for stroke is desirable but will likely require multiple proteins rather than a single "troponin." Validating large protein panels requires large patient numbers. Mass spectrometry (MS) is a cost-effective tool for this task. We compared differences in the abundance of 147 protein markers to distinguish 20 acute cerebrovascular syndrome (ACVS) patients who presented to the Emergency Department of one urban hospital within < 24 h from onset) and from 20 control patients who were enrolled via an outpatient neurology clinic. We targeted proteins from the stroke literature plus cardiovascular markers previously studied in our lab. One hundred forty-one proteins were quantified using MS, 8 were quantified using antibody protein enrichment with MS, and 32 were measured using ELISA, with some proteins measured by multiple techniques. Thirty proteins (4 by ELISA and 26 by the MS techniques) were differentially abundant between mimic and stroke after adjusting for age in robust regression analyses (FDR < 0.20). A logistic regression model using the first two principal components of the proteins significantly improved discrimination between strokes and controls compared to a model based on age alone (p < 0.001, cross-validated AUC 0.93 vs. 0.78). Significant proteins included markers of inflammation (47%), coagulation (40%), atrial fibrillation (7%), neurovascular unit injury (3%), and other (3%). These results suggest the potential value of plasma proteins as biomarkers for ACVS diagnosis and the role of plasma-based MS in this area.

Comparing variational Bayes with Markov chain Monte Carlo for Bayesian computation in neuroimaging.

In this article, we consider methods for Bayesian computation within the context of brain imaging studies. In such studies, the complexity of the resulting data often necessitates the use of sophisticated statistical models; however, the large size of these data can pose significant challenges for model fitting. We focus specifically on the neuroelectromagnetic inverse problem in electroencephalography, which involves estimating the neural activity within the brain from electrode-level data measured across the scalp. The relationship between the observed scalp-level data and the unobserved neural activity can be represented through an underdetermined dynamic linear model, and we discuss Bayesian computation for such models, where parameters represent the unknown neural sources of interest. We review the inverse problem and discuss variational approximations for fitting hierarchical models in this context. While variational methods have been widely adopted for model fitting in neuroimaging, they have received very little attention in the statistical literature, where Markov chain Monte Carlo is often used. We derive variational approximations for fitting two models: a simple distributed source model and a more complex spatiotemporal mixture model. We compare the approximations to Markov chain Monte Carlo using both synthetic data as well as through the analysis of a real electroencephalography dataset examining the evoked response related to face perception. The computational advantages of the variational method are demonstrated and the accuracy associated with the resulting approximations are clarified.

Mega-dose vitamins and minerals in the treatment of non-metastatic breast cancer: an historical cohort study.

BACKGROUND: Alternative therapies such as mega-dose vitamins and minerals are commonly used by women with breast cancer, but their effect on recurrence and survival have rarely been evaluated. METHODS: Survival and recurrence outcomes for 90 women with unilateral non-metastatic breast cancer diagnosed between 1989 and 1998, and who had been prescribed mega-doses of beta-carotene, vitamin C, niacin, selenium, coenzyme Q10, and zinc in addition to standard therapies were compared with matched controls. The 90 treated patients were prescribed combinations from three to six of the vitamins and minerals listed above. The controls were matched (2:1) to the vitamin/mineral patients for age at diagnosis, presence of axillary lymph node metastasis, tumor stage, grade, estrogen receptor status, year of diagnosis, and prescription of systemic therapy. All subjects were patients of the British Columbia Cancer Agency, Vancouver Island Centre. FINDINGS: Median follow-up of surviving patients was 68 months (minimum 20 months, 133 months maximum). The vitamin/mineral patients and controls were well matched. Two endpoints were considered. Breast cancer-specific survival (p = 0.19) and disease-free survival (p = 0.08) times for the vitamin/mineral treated group were shorter, after adjusting for diagnostic variables using a Cox proportional hazards model. The hazard ratios for the vitamin/mineral treated group versus the control group were estimated at 1.75 (95% CI = 0.83-2.69) for disease-specific survival and 1.55 (95% CI = 0.94-2.54) for disease-free survival. Overall survival was similar for the two groups (log-rank test, p = 0.36). INTERPRETATION: Breast cancer-specific survival and disease-free survival times were not improved for the vitamin/mineral treated group over those for the controls.

NSABP trials of adjuvant chemotherapy for breast cancer. A further look at the evidence.

Two decades ago the National Surgical Adjuvant Breast Project (NSABP) began to test the hypothesis that adjuvant chemotherapy would influence favorably the postsurgical survival rates of women with breast cancer. Although the use of phenylalanine mustard (melphalan or (L-PAM) has been supplemented by other agents, the thrust to recommend adjuvant chemotherapy as standard treatment was created by an L-PAM series of five trials using L-PAM or L-PAM plus fluorouracil. Only the first trial, B-05, contained an untreated group. The main treated groups in these five trials are similar to each other in survival probabilities, and the main untreated group in B-05 is not different in survival than the combined results of these five trials. There were a total of nine comparison in each study-and in B-05 the subgroup of treated women 49 years or younger with one to three positive node was found to be different than the untreated group. Four subsequent subgroups of women who were 49 years or younger with one to three positive nodes are not similar in survival despite the fact that they were developed from similar main groups that had similar treatment. The initial treated subgroup in B-05 had a survival outcome that was never again achieved in the subsequent four studies. The untreated subgroup in B-05 was not different than three of the four subsequently treated subgroups. The NSABP now has evidence that denies the conclusion that adjuvant chemotherapy prolongs survival in premenopausal node-positive women. Recommendations that adjuvant chemotherapy become standard treatment for premenopausal node-positive women should be seriously reconsidered and probably withdrawn.