Performance of a genetic algorithm for mass spectrometry proteomics

Abstract Background Recently, mass spectrometry data have been mined using a genetic algorithm to produce discriminatory models that distinguish healthy individuals from those with cancer. This algorithm is the basis for claims of 100% sensitivity and specificity in two related publicly available datasets. To date, no detailed attempts have been made to explore the properties of this genetic algorithm within proteomic applications. Here the algorithm's performance on these datasets is evaluated relative to other methods. Results In reproducing the method, some modifications of the algorithm as it is described are necessary to get good performance. After modification, a cross-validation approach to model selection is used. The overall classification accuracy is comparable though not superior to other approaches considered. Also, some aspects of the process rely upon random sampling and thus for a fixed dataset the algorithm can produce many different models. This raises questions about how to choose among competing models. How this choice is made is important for interpreting sensitivity and specificity results as merely choosing the model with lowest test set error rate leads to overestimates of model performance. Conclusions The algorithm needs to be modified to reduce variability and care must be taken in how to choose among competing models. Results derived from this algorithm must be accompanied by a full description of model selection procedures to give confidence that the reported accuracy is not overstated.</p

Do we need gastric acid?

Evidence from comparative anatomy and physiology studies indicates that gastric acid secretion developed during the evolution of vertebrates approximately 350 million years ago. The cellular mechanisms that produce gastric acid have been conserved over the millennia and therefore proton pump inhibitors have pharmacological effects in almost all relevant species. These observations suggest that gastric acid provides an important selective advantage; however, in modern-day humans the need for gastric acid can be questioned in light of the widespread use of safe and effective pharmacologic acid suppression. The Kandahar Working Group addressed questions concerning the need, production and effects of gastric acid, specifically: (1) motility in the upper gastrointestinal (GI) tract; (2) neuroendocrine factors; (3) digestive and mucosal processes; (4) microbiology, and (5) central processes and psychological involvement. We addressed each topic with the individual models available to answer our questions including animal versus human studies, pharmacologic, surgical as well as pathophysiologic states of acid suppression

Rate Control versus Rhythm Control for Atrial Fibrillation after Cardiac Surgery

BACKGROUND Atrial fibrillation after cardiac surgery is associated with increased rates of death, complications, and hospitalizations. In patients with postoperative atrial fibrillation who are in stable condition, the best initial treatment strategy -heart-rate control or rhythm control -remains controversial. METHODS Patients with new-onset postoperative atrial fibrillation were randomly assigned to undergo either rate control or rhythm control. The primary end point was the total number of days of hospitalization within 60 days after randomization, as assessed by the Wilcoxon rank-sum test. RESULTS Postoperative atrial fibrillation occurred in 695 of the 2109 patients (33.0%) who were enrolled preoperatively; of these patients, 523 underwent randomization. The total numbers of hospital days in the rate-control group and the rhythm-control group were similar (median, 5.1 days and 5.0 days, respectively; P = 0.76). There were no significant between-group differences in the rates of death (P = 0.64) or overall serious adverse events (24.8 per 100 patient-months in the rate-control group and 26.4 per 100 patient-months in the rhythm-control group, P = 0.61), including thromboembolic and bleeding events. About 25% of the patients in each group deviated from the assigned therapy, mainly because of drug ineffectiveness (in the rate-control group) or amiodarone side effects or adverse drug reactions (in the rhythm-control group). At 60 days, 93.8% of the patients in the rate-control group and 97.9% of those in the rhythm-control group had had a stable heart rhythm without atrial fibrillation for the previous 30 days (P = 0.02), and 84.2% and 86.9%, respectively, had been free from atrial fibrillation from discharge to 60 days (P = 0.41). CONCLUSIONS Strategies for rate control and rhythm control to treat postoperative atrial fibrillation were associated with equal numbers of days of hospitalization, similar complication rates, and similarly low rates of persistent atrial fibrillation 60 days after onset. Neither treatment strategy showed a net clinical advantage over the other