Stephen W. Looney

An application of the cox proportional hazards model to bank failure

The purpose of this study is to present the Cox proportional hazards model and to apply this model to the prediction of bank failures. The Cox model, which has been used extensively in biomedical applications, has not been previously employed in the finance literature. The principal advantage of the Cox model over other classification techniques is that it models the expected time to failure. Results of the study indicate that total classification accuracy of the Cox model is similar to that of discriminant analysis, although the Cox model produces somewhat lower type I errors. In a comparison of actual and predicted times to failure, the Cox model tends to identify bankruptcies prior to the actual failure date.

Poor validity of residual volumes as a marker for risk of aspiration in critically ill patients.

Background and Aims:Elevated residual volumes (RV), considered a marker for the risk of aspiration, are used to regulate the delivery of enteral tube feeding. We designed this prospective study to validate such use. Methods:Critically ill patients undergoing mechanical ventilation in the medical, coronary, or surgical intensive care units in a university-based tertiary care hospital, placed on intragastric enteral tube feeding through nasogastric or percutaneous endoscopic gastrostomy tubes, were included in this study. Patients were fed Probalance (Nestlé USA) to provide 25 kcal/kg per day (to which 109 yellow microscopic beads and 4.5 mL of blue food coloring per 1,500 mL was added). Patients were randomized to one of two groups based on management of RV: cessation of enteral tube feeding for RV >400 mL in study patients or for RV >200 mL in controls. Acute Physiology and Chronic Health Evaluation (APACHE) III, bowel function score, and aspiration risk score were determined. Bedside evaluations were done every 4 hrs for 3 days to measure RV, to detect blue food coloring, to check patient position, and to collect secretions from the trachea and oropharynx. Aspiration/regurgitation events were defined by the detection of yellow color in tracheal/oropharyngeal samples by fluorometry. Analysis was done by analysis of variance, Spearman’s correlation, Student’s t-test, Tukey’s method, and Cochran-Armitage test. Results:Forty patients (mean age, 44.6 yrs; range, 18–88 yrs; 70% male; mean APACHE III score, 40.9 [range, 12–85]) were evaluated (21 on nasogastric, 19 on percutaneous endoscopic gastrostomy feeds) and entered into the study. Based on 1,118 samples (531 oral, 587 tracheal), the mean frequency of regurgitation per patient was 31.3% (range, 0% to 94%), with a mean RV for all regurgitation events of 35.1 mL (range, 0–700 mL). The mean frequency of aspiration per patient was 22.1% (range, 0% to 94%), with a mean RV for all aspiration events of 30.6 mL (range, 0–700 mL). The median RV for both regurgitation and aspiration events was 5 mL. Over a wide range of RV, increasing from 0 mL to >400 mL, the frequency of regurgitation and aspiration did not change appreciably. Aspiration risk and bowel function scores did not correlate with the incidence of aspiration or regurgitation. Blue food coloring was detected on only three of the 1,118 (0.27%) samples. RV was ≤50 mL on 84.1% and >400 mL on 1.4% of bedside evaluations. Sensitivities for detecting aspiration per designated RV were as follows: 400 mL = 1.5%; 300 mL = 2.3%; 200 mL = 3.0%; and 150 mL = 4.5%. Low RV did not assure the absence of events, because the frequency of aspiration was 23.0% when RV was <150 mL. Raising the designated RV for cessation of enteral tube feeding from 200 mL to 400 mL did not increase the risk, because the frequency of aspiration was no different between controls (21.6%) and study patients (22.6%). The frequency of regurgitation was significantly less for patients with percutaneous endoscopic gastrostomy tubes compared with those with nasogastric tubes (20.3% vs. 40.7%, respectively; p = .046). There was no correlation between the incidence of pneumonia and the frequency of regurgitation or aspiration. Conclusions:Blue food coloring should not be used as a clinical monitor. Converting nasogastric tubes to percutaneous endoscopic gastrostomy tubes may be a successful strategy to reduce the risk of aspiration. No appropriate designated RV level to identify aspiration could be derived as a result of poor sensitivity over a wide range of RV. Study results do not support the conventional use of RV as a marker for the risk of aspiration.

A Retrospective Review of 61 Patients With Antiphospholipid Syndrome Analysis of Factors Influencing Recurrent Thrombosis

BACKGROUND Antiphospholipid syndrome (APS) is a disorder of recurrent venous or arterial thrombosis, pregnancy losses, and thrombocytopenia. Recurrent thrombosis has particularly adverse effects on patients prognosis. The factors that influence recurrence and management techniques that prevent these events remain controversial. To add further insight regarding predisposing factors and the prevention of thrombotic recurrence, 61 well-characterized patients with APS were followed up for a median time of 77 months. METHODS A retrospective cohort study was conducted in which the following factors were examined to determine their influence on thrombotic recurrence: primary vs secondary syndrome; the presence of hypertension, hyperlipidemia, diabetes, or smoking; patient age, sex, and race; pregnancy and oral contraceptives use; and treatment with warfarin sodium, warfarin plus aspirin, aspirin alone, prednisone, or no treatment. RESULTS There was no difference between patients with primary and secondary APS with respect to recurrent arterial (55% vs 38%, respectively) or recurrent venous (47% vs 50%, respectively) thrombotic events. In all patients with APS, white race (P = .02) was associated with recurrent arterial events. Venous thrombosis occurred during pregnancy or in the postpartum period in 16 (30%) of 53 women and in 8 women taking oral contraceptives. Recurrent arterial and venous thromboses were significantly decreased with prophylactic warfarin use when compared with prednisone use or no treatment. Recurrences were infrequent in patients with prothrombin ratios of 1.5 to 2.0. CONCLUSIONS Treatment with warfarin was most effective in preventing recurrent arterial and venous thrombosis. Pregnancy and the use of oral contraceptives or prednisone may also influence recurrence.

Use of the Correlation Coefficient with Normal Probability Plots

Abstract The use of the correlation coefficient is suggested as a technique for summarizing and objectively evaluating the information contained in probability plots. Goodness-of-fit tests are constructed using this technique for several commonly used plotting positions for the normal distribution. Empirical sampling methods are used to construct the null distribution for these tests, which are then compared on the basis of power against certain nonnormal alternatives. Commonly used regression tests of fit are also included in the comparisons. The results indicate that use of the plotting position pi = (i - .375)/(n + .25) yields a competitive regression test of fit for normality.

The requirement of zinc and calcium ions for functional MMP activity in demineralized dentin matrices

UNLABELLED The progressive degradation of resin-dentin bonds is due, in part, to the slow degradation of collagen fibrils in the hybrid layer by endogenous matrix metalloproteinases (MMPs) of the dentin matrix. In in vitro durability studies, the storage medium composition might be important because the optimum activity of MMPs requires both zinc and calcium. OBJECTIVE This study evaluated the effect of different storage media on changes in matrix stiffness, loss of dry weight or solubilization of collagen from demineralized dentin beams incubated in vitro for up to 60 days. METHODS Dentin beams (1mm×2mm×6mm) were completely demineralized in 10% phosphoric acid. After baseline measurements of dry mass and elastic modulus (E) (3-point bending, 15% strain) the beams were divided into 5 groups (n=11/group) and incubated at 37°C in either media containing both zinc and calcium designated as complete medium (CM), calcium-free medium, zinc-free medium, a doubled-zinc medium or water. Beams were retested at 3, 7, 14, 30, and 60 days of incubation. The incubation media was hydrolyzed with HCl for the quantitation of hydroxyproline (HOP) as an index of solubilization of collagen by MMPs. Data were analyzed using repeated measures of ANOVA. RESULTS Both the storage medium and the storage time showed significant effects on E, mass loss and HOP release (p<0.05). The incubation in CM resulted in relatively rapid and significant (p<0.05) decreases in stiffness, and increasing amounts of mass loss. The HOP content of the experimental media also increased with incubation time but was significantly lower (p<0.05) than in the control CM medium, the recommended storage medium. CONCLUSIONS The storage solutions used to age resin-dentin bonds should be buffered solutions that contain both calcium and zinc. The common use of water as an aging medium may underestimate the hydrolytic activity of endogenous dentin MMPs.

Warfarin dose adjustments based on CYP2C9 genetic polymorphisms

AbstractBackground: The dose response relationship of warfarin is unpredictable. Polymorphism of the Cytochrome P4502C9 enzyme leads to warfarin hypersensitivity presumably due to decreased metabolism of the S-enantiomer. The purpose of this study was to further characterize the relationship between CYP2C9 genotype and phenotype and to develop a basis for guidelines to interpret CYP2C9 genotype for warfarin dosing. Methods and results: Patients stabilized on warfarin therapy were recruited from an anticoagulation clinic. Patients were genotyped for CYP2C9*2, CYP2C9*3 and CYP2C9*5 alleles by standard methods of polymerase chain reaction amplification and restriction endonuclease digestion. Phenotype was determined by; dose (mg/kg/d) required to maintain anticoagulation, (INR 2.0–3.0), oral plasma S-warfarin clearance, and the plasma S:R-warfarin ratio. In this cohort, no subjects were found to have the CYP2C9*5 allele. The plasma S-warfarin concentration did not differ with age, dose or CYP2C9 genotype. Both CYP2C9*2 and *3 alleles were associated with lower maintenance dosages, lower total and R-warfarin plasma concentrations, decreased oral clearance of S-warfarin, increased plasma S:R-warfarin ratio and extended S-warfarin elimination half-life. Advancing age was found to decrease Warfarin maintenance dose in subjects with the common active CYP2C9*1/*1 genotype but did not influence dose requirement of subjects with one or more variant CYP2C9 alleles. Conclusions: Subjects who have been titrated to a consistent target INR demonstrate comparable plasma S-warfarin concentrations independent of CYP2C9 genotype. The warfarin dose required to maintain a consistent target INR between subjects differs as a function of S-warfarin clearance which is decreased by both CYP2C9*2 and or CYP2C9*3 variant alleles. The variables of CYP2C9 genotype and age can be applied to restrict the dosage range considered for individual patients.

Setting Properties and Cytotoxicity Evaluation of a Premixed Bioceramic Root Canal Sealer

INTRODUCTION This study investigated the setting time and micohardness of a premixed calcium phosphate silicate-based sealer (EndoSequence BC Sealer; Brasseler USA, Savannah, GA) in the presence of different moisture contents (0-9 wt%). The moisture content that produced the most optimal setting properties was used to prepare set EndoSequence BC Sealer for cytotoxicity comparison with an epoxy resin-based sealer (AH Plus; Dentsply Caulk, Milford, DE). METHODS Standardized disks were created with BC Sealer, AH Plus, Pulp Canal Sealer EWT (positive control) (SybronEndo, Orange CA), and Teflon (Small Parts Inc., Miami Lakes, FL; negative control). Disks were placed in Transwell Inserts, providing indirect contact with MC3T3-E1 cells. Succinate dehydrogenase activity of the cells was evaluated over a 6-week period using MTT ((3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cytotoxicity profiles of BC Sealer and AH Plus were fitted with polynomial regression models. The time for 50% of the cells to survive (T(0.5)) was analyzed using the Wald statistic with a two-tailed significance level of 0.05. RESULTS BC Sealer required at least 168 hours to reach the final setting using the Gilmore needle method, and its microhardeness significantly declined when water was included in the sealer (P = .004). All set sealers exhibited severe cytotoxicity at 24 hours. The cytotoxicity of AH Plus gradually decreased and became noncytotoxic, whereas BC Sealer remained moderately cytotoxic over the 6-week period. A significant difference (P < .001) was detected between T(0.5) of BC Sealer (5.10 weeks; 95% confidence interval [CI], 4.69-5.42, standard error [SE] = 0.09) and T(0.5) of AH Plus (0.86 weeks; 95% CI, 0.68-1.05; SE = 0.18). CONCLUSIONS Further studies are required to evaluate the correlation between the length of setting time of BC Sealer and its degree of cytotoxicity.

Chlorhexidine binding to mineralized versus demineralized dentin powder

OBJECTIVES The purposes of this work were to quantitate the affinity and binding capacity of chlorhexidine (CHX) digluconate to mineralized versus demineralized dentin powder and to determine how much debinding would result from rinsing with water, ethanol, hydroxyethylmethacrylate (HEMA) or 0.5M NaCl in water. METHODS Dentin powder was made from coronal dentin of extracted human third molars. Standard amounts of dentin powder were tumbled with increasing concentrations of CHX (0-30 mM) for 30 min at 37 degrees C. After centrifuging the tubes, the supernatant was removed and the decrease in CHX concentration quantitated by UV-spectroscopy. CHX-treated dentin powder was resuspended in one of the four debinding solutions for 3 min. The amount of debound CHX in the solvents was also quantitated by UV-spectroscopy. RESULTS As the CHX concentration in the medium increased, the CHX binding to mineralized dentin powder also increased up to 6.8 micromol/g of dry dentin powder. Demineralized dentin powder took up significantly (p<0.01) more CHX, reaching 30.1 micromol CHX/g of dry dentin powder. Debinding of CHX was in the order: HEMA<ethanol<0.05 M NaCl<water. The highest CHX binding to demineralized dentin occurred at 30 mM (1.5 wt.%). SIGNIFICANCE As CHX is not debound by HEMA, it may remain bound to demineralized dentin during resin-dentin bonding. This may be responsible for the long-term efficacy of CHX as an MMP inhibitor in resin-dentin bonds.

How to Use Tests for Univariate Normality to Assess Multivariate Normality

Abstract The assumption of multivariate normality (MVN) underlies many important techniques in multivariate analysis. In the past 50 years, over 50 tests of this assumption have been proposed. However, for various reasons, practitioners are often reluctant to address the MVN issue. In this article, several techniques for assessing MVN based on well-known tests for univariate normality are described and suggestions are offered for their practical application. The techniques are illustrated using two previously published sets of real-life data. In one of the examples it is shown that simply testing each of the marginal distributions for univariate normality can lead to a mistaken conclusion.

Comparison of incidence of invasive Streptococcus pneumoniae disease among children before and after introduction of conjugated pneumococcal vaccine

Objectives: The objective was to determine whether there has been a significant decrease in the incidence of invasive Streptococcus pneumoniae disease in the Louisville, KY, area since heptavalent pneumococcal conjugate vaccine was introduced in the winter of 1999–2000. A secondary objective was to collect demographic data regarding invasive S. pneumoniae disease in the Louisville, KY, area during the 1997–2002 period. Methods: Data on cases of invasive S. pneumoniae disease (defined by a positive culture for S. pneumoniae from the blood, pleural fluid or cerebrospinal fluid) were collected from the microbiology laboratories and medical records departments of all hospitals that treat children in the Louisville area, for 1997–2002. Trends in case rates for all cases of invasive S. pneumoniae disease from 1999 to 2002 were observed, and demographic and other factors regarding this illness were recorded for each patient. Results: The trend for rates of invasive pneumococcal disease showed a significant decrease during the study period for all ages combined (P < 0.001), for children younger than 2 years of age (P = 0.002) and for children 2 to 5 years of age (P = 0.002). The mean age for children was 2.22 years, with a male/female ratio of 1.8:1. The most common final diagnoses for the patients were bacteremia without focus, pneumonia and meningitis. Forty-eight percent of the organisms were resistant to penicillin. There was a significantly higher rate of resistance to penicillin among S. pneumoniae strains that caused cerebrospinal fluid infection than among strains that caused non-cerebrospinal fluid infection (P < 0.001). The case fatality rate was 2.6%. Conclusion: Case rates for invasive S. pneumoniae disease among children decreased significantly in the 2-year period after introduction of the heptavalent S. pneumonia protein conjugate vaccine into this community.