Using Diversity Ensembles with Time Limits to Handle Concept Drift

While traditional supervised learning focuses on static datasets, an increasing amount of data comes in the form of streams, where data is continuous and typically processed only once. A common problem with data streams is that the underlying concept we are trying to learn can be constantly evolving. This concept drift has been of interest to researchers the last few years and there is a need for improved machine learning algorithms that are capable of dealing with concept drifts. A promising approach involves using an ensemble of a diverse set of classifiers. The constituent classifiers are re-trained when a concept drift is detected. Decisions regarding the number of classifiers to maintain and the frequency of re-training classifiers are critical factors that determine classification accuracy in the presence of concept drift. This dissertation systematically investigated these issues in order to develop an improved classifier for online ensemble learning. The impact of reducing the time requiring additional ensembles was studied using artificial and real world datasets. Findings from these studies revealed that in many cases the number of time steps additional ensembles are in memory can be reduced without sacrificing prequential accuracy. It was also found that this new ensemble approach performed well in the presence of false concept drift

Preliminary Characterization of Voltage-Activated Whole-Cell Currents in Developing Human Vestibular Hair Cells and Calyx Afferent Terminals

We present preliminary functional data from human vestibular hair cells and primary afferent calyx terminals during fetal development. Whole-cell recordings were obtained from hair cells or calyx terminals in semi-intact cristae prepared from human fetuses aged between 11 and 18 weeks gestation (WG). During early fetal development (11–14 WG), hair cells expressed whole-cell conductances that were qualitatively similar but quantitatively smaller than those observed previously in mature rodent type II hair cells. As development progressed (15–18 WG), peak outward conductances increased in putative type II hair cells but did not reach amplitudes observed in adult human hair cells. Type I hair cells express a specific low-voltage activating conductance, G(K,L). A similar current was first observed at 15 WG but remained relatively small, even at 18 WG. The presence of a “collapsing” tail current indicates a maturing type I hair cell phenotype and suggests the presence of a surrounding calyx afferent terminal. We were also able to record from calyx afferent terminals in 15–18 WG cristae. In voltage clamp, these terminals exhibited fast inactivating inward as well as slower outward conductances, and in current clamp, discharged a single action potential during depolarizing steps. Together, these data suggest the major functional characteristics of type I and type II hair cells and calyx terminals are present by 18 WG. Our study also describes a new preparation for the functional investigation of key events that occur during maturation of human vestibular organs

A microdialysis study of ventral striatal dopamine during sexual behavior in female Syrian hamsters

Microdialysis was used to study the effects of exposure to a male hamster on extracellular concentrations of dopamine, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) in the ventral striatum of ovariectomized female Syrian hamsters pretreated with either estradiol and progesterone, or a similar regimen of oil injections. The hormone-treated females showed high levels of lordosis throughout the hour of exposure to the male. In hormone-treated females, there was a rapid elevation of dialysate dopamine within the first 15 min of exposure to the male. Dialysate dopamine gradually declined over the next 45 min, though remaining significantly above baseline during the entire period of exposure to the male. None of the oil-treated females showed any indication of lordosis, and the addition of the male produced only a small increase in dopamine at 30 min, after which dopamine returned to pre-male basal levels. DOPAC, HVA, and 5-HIAA were all elevated following introduction of the male for both groups of females. These results suggest that ovarian hormones modulate the responsivity of ventral striatal dopamine to incentive stimuli associated with mating behavior in females, although extracellular levels of dopamine in the ventral striatum do not seem to be directly coupled to the display of lordosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30731/1/0000380.pd

Bacterial translocation in the newborn rabbit: effect of age on frequency of translocation

Sepsis is a significant cause of morbidity and mortality in neonates, and in a significant number of cases no predisposing factors can be identified. We hypothesize that bacterial translocation (BT) may be the etiology of neonatal sepsis when no source is identified. Mesenteric lymph nodes (MLN), spleen (SPL), and liver (LIV) were harvested from 36 rabbit pups ranging in age from 4 to 24 days and divided into three groups based on their age: group I, 4–6 days; group II, 13–15 days; and group III, 22–24 days. Tissues from each organ were homogenized and placed in both aerobic and anaerobic environments. After 48 h the number of colony-forming units/g tissue was identified. The total percentage of positive growth was significantly higher in group I for MLN (33%) and LIV (23%) when compared to groups II and III (<4% for both groups). Gram-negative growth (as selected by MacConkey [MC] media) was significantly higher in all tissue specimens from group I (MLN + 35%, SPL = 20%, LIV = 25%) compared to groups II and III (0% growth in all MC plates, P <0.01). These data support the hypothesis that spontaneous BT occurs with significant frequency in the neonate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47149/1/383_2004_Article_BF00171174.pd

Quality improvement program decreases mortality after cardiac surgery

ObjectiveThis study investigated the effects of a quality improvement program and goal-oriented, multidisciplinary protocols on mortality after cardiac surgery.MethodsPatients were divided into two groups: those undergoing surgery (coronary artery bypass grafting, isolated valve surgery, or coronary artery bypass grafting and valve surgery) after establishment of the multidisciplinary quality improvement program (January 2005–December 2006, n = 922) and those undergoing surgery before institution of the program (January 2002–December 2003, n = 1289). Logistic regression and propensity score analysis were used to adjust for imbalances in patients' preoperative characteristics.ResultsOperative mortality was lower in the quality improvement group (2.6% vs 5.0%, P < .01). Unadjusted odds ratio was 0.5 (95% confidence interval 0.3–0.8, P < .01); propensity score–adjusted odds ratio was 0.6 (95% confidence interval 0.4–0.99, P = .04). In multivariable analysis, diabetes (P < .01), chronic renal insufficiency (P = .05), previous cardiovascular operation (P = .04), congestive heart failure (P < .01), unstable angina (P < .01), age older than 75 years (P < .01), prolonged pump time (P < .01), and prolonged operation (P = .05) emerged as independent predictors of higher mortality after cardiac surgery, whereas quality improvement program (P < .01) and male sex (P = .03) were associated with lower mortality. Mortality decline was less pronounced in patients with than without diabetes (P = .04).ConclusionApplication of goal-directed, multidisciplinary protocols and a quality improvement program were associated with lower mortality after cardiac surgery. This decline was less prominent in patients with diabetes, and focused quality improvement protocols may be required for this subset of patients

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al

Colonization of intestinal bacteria in the normal neonate: Comparison between mouth and rectal swabs and small and large bowel specimens

Seventy-four New Zealand white rabbit pups were divided into four groups: group I, 2 days of age (n = 9); group II, 3 to 5 days of age (n = 24); group III, 6 to 8 days of age (n = 27); and group IV, 10 to 13 days of age (n = 14). Mouth swabs (MS), rectal swabs (RS), small bowel specimens (SB), and large bowel specimens (LB) were obtained from each rabbit, incubated for 24 hours in thioglycolate broth, and plated on blood agar in aerobic and anaerobic environments. After 24 hours, growth on blood agar plates were observed. All MS specimens and all but one RS specimen showed positive growth. Growth of both LB and SB specimens increased significantly with age (P P P v 100% and 93% v 100%, respectively). These data show that nearly half of normal rabbits under 6 days of age have sterile small and large intestines despite almost 100% growth from rectal and mouth swabs. These findings partially explain the absence of spontaneous bacterial translocation in young rabbit pups (under 4 days of age) and have important implications for the prophylaxis and treatment of neonatal sepsis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31313/1/0000222.pd

Tumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell Carcinoma Patients Treated on ECOG-ACRIN E2805

Purpose—Increased vascularity is a hallmark of renal cell carcinoma (RCC). Microvessel density (MVD) is one measurement of tumor angiogenesis; however, its utility as a biomarker of outcome is unknown. ECOG-ACRIN 2805 (E2805) enrolled 1,943 resected high-risk RCC patients randomized to adjuvant sunitinib, sorafenib, or placebo. We aimed to determine the prognostic and predictive role of MVD in RCC. Experimental Design—We obtained pretreatment primary RCC nephrectomy tissues from 822 patients on E2805 and constructed tissue microarrays. Using quantitative immunofluorescence, we measured tumor MVD as the area of CD34-expressing cells. We determined the association with disease-free survival (DFS), overall survival (OS), treatment arm, and clinicopathologic variables. Results—High MVD (above the median) was associated with prolonged OS for the entire cohort (p = 0.021) and for patients treated with placebo (p = 0.028). The association between high MVD and OS was weaker in patients treated with sunitinib or sorafenib (p = 0.060). MVD was not associated with DFS (p = 1.00). On multivariable analysis, MVD remained independently associated with improved OS (p = 0.013). High MVD correlated with Fuhrman grade 1–2 (p \u3c 0.001), clear cell histology (p \u3c 0.001), and absence of necrosis (p \u3c 0.001) but not with gender, age, sarcomatoid features, lymphovascular invasion, or tumor size. Conclusions—High MVD in resected high-risk RCC patients is an independent prognostic, rather than predictive, biomarker of improved OS. Further studies should assess whether incorporating MVD into clinical models will enhance our ability to predict outcome and if low MVD can be used for selection of high-risk patients for adjuvant therapy trials