Showing papers by "University at Buffalo published in 2004"

Mining Frequent Patterns without Candidate Generation: A Frequent-Pattern Tree Approach

Abstract: Mining frequent patterns in transaction databases, time-series databases, and many other kinds of databases has been studied popularly in data mining research. Most of the previous studies adopt an Apriori-like candidate set generation-and-test approach. However, candidate set generation is still costly, especially when there exist a large number of patterns and/or long patterns. In this study, we propose a novel frequent-pattern tree (FP-tree) structure, which is an extended prefix-tree structure for storing compressed, crucial information about frequent patterns, and develop an efficient FP-tree-based mining method, FP-growth, for mining the complete set of frequent patterns by pattern fragment growth. Efficiency of mining is achieved with three techniques: (1) a large database is compressed into a condensed, smaller data structure, FP-tree which avoids costly, repeated database scans, (2) our FP-tree-based mining adopts a pattern-fragment growth method to avoid the costly generation of a large number of candidate sets, and (3) a partitioning-based, divide-and-conquer method is used to decompose the mining task into a set of smaller tasks for mining confined patterns in conditional databases, which dramatically reduces the search space. Our performance study shows that the FP-growth method is efficient and scalable for mining both long and short frequent patterns, and is about an order of magnitude faster than the Apriori algorithm and also faster than some recently reported new frequent-pattern mining methods.

Scoring function for automated assessment of protein structure template quality

Abstract: We have developed a new scoring function, the template modeling score (TM-score), to assess the quality of protein structure templates and predicted full-length models by extending the approaches used in Global Distance Test (GDT) 1 and MaxSub. 2 First, a protein size-dependent scale is exploited to eliminate the inherent protein size dependence of the previous scores and appropri- ately account for random protein structure pairs. Second, rather than setting specific distance cutoffs and calculating only the fractions with errors below the cutoff, all residue pairs in alignment/modeling are evaluated in the proposed score. For compari- son of various scoring functions, we have con- structed a large-scale benchmark set of structure templates for 1489 small to medium size proteins using the threading program PROSPECTOR_3 and built the full-length models using MODELLER and TASSER. The TM-score of the initial threading align- ments, compared to the GDT and MaxSub scoring functions, shows a much stronger correlation to the quality of the final full-length models. The TM-score is further exploited as an assessment of all 'new fold' targets in the recent CASP5 experiment and shows a close coincidence with the results of human-expert visual assessment. These data suggest that the TM- score is a useful complement to the fully automated assessment of protein structure predictions. The executable program of TM-score is freely download- able at http://bioinformatics.buffalo.edu/TM-score. aligned, the resulting full-length model might be of poorer quality. The template assessment problem becomes particu- larly relevant during the development of efficient fold recognition algorithms, since different sequence-structure alignment schemes or parameters can result in various levels of alignment confidence with an associated loss or gain of alignment coverage. 3- 6 Therefore, a single assess- ment score that has an appropriate balance of alignment accuracy and coverage and that is strongly related to the quality of the final full-length model is essential. Equally important, it must differentiate between a random and a statistically significant prediction. Highly related to the above problems, several interest- ing scoring functions have been developed for the purpose of sequence-dependent comparison of two structures of different lengths (in contrast to sequence-independent

The Collaborative Cross, a community resource for the genetic analysis of complex traits

Abstract: The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.

Relationship of MIC and Bactericidal Activity to Efficacy of Vancomycin for Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

Abstract: We attempted to find a relationship between the microbiological properties of bloodstream isolates of methicillin-resistant Staphylococcus aureus (MRSA) and the efficacy of vancomycin in the treatment of bacteremia. Vancomycin susceptibility testing was performed, and bactericidal activity was determined for 30 isolates from 30 different patients with MRSA bacteremia for whom clinical and microbiological outcome data were available. The majority of these patients had been previously enrolled in multicenter prospective studies of MRSA bacteremia refractory to conventional vancomycin therapy. Logistic regression found a statistically significant relationship between treatment success with vancomycin and decreases in both vancomycin MICs (≤0.5 μg/ml versus 1.0 to 2.0 μg/ml; P = 0.02) and degree of killing (reduction in 1og10 CFU/milliliter) by vancomycin over 72 h of incubation in vitro (P = 0.03). For MRSA isolates with vancomycin MICs ≤ 0.5 μg/ml, vancomycin was 55.6% successful in the treatment of bacteremia whereas vancomycin was only 9.5% effective in cases in which vancomycin MICs for MRSA were 1 to 2 μg/ml. Patients with MRSA that was more effectively killed at 72 h by vancomycin in vitro had a higher clinical success rate with vancomycin therapy in the treatment of bacteremia (log10 6.27 [n = 8], 50%). We conclude that a significant risk for vancomycin treatment failure in MRSA bacteremia begins to emerge with increasing vancomycin MICs well within the susceptible range. Elucidating the mechanisms involved in intermediate-level glycopeptide resistance in S. aureus should begin by examining bacteria that begin to show changes in vancomycin susceptibility before the development of obvious resistance. Prognostic information for vancomycin treatment outcome in MRSA bacteremia may also be obtained by testing the in vitro bactericidal potency of vancomycin.

Mushrooms: Cultivation, Nutritional Value, Medicinal Effect, and Environmental Impact

Abstract: Since the publication of the first edition, important developments have emerged in modern mushroom biology and world mushroom production and products. The relationship of mushrooms with human welfare and the environment, medicinal properties of mushrooms, and the global marketing value of mushrooms and their products have all garnered great attenti

Enyne Metathesis (Enyne Bond Reorganization)

Abstract: Enyne metathesis is a bond reorganization of an alkene and an alkyne to produce a 1,3-diene (eqs 1 and 2 in Scheme 1). It has been used in both intramolecular and intermolecular applications. Enyne metathesis bears a mechanistic kinship to alkene metathesis; however, it is less-studied than alkene metathesis. The enyne bond reorganization is atom economical and is driven by the enthalpic stability of the conjugated 1,3-diene produced. Stereoselection is often low in intermolecular cases but can be controlled in intramolecular cases. The enyne metathesis can be catalyzed by metal carbenes or “templated” by metal salts. Many of the same metal carbenes that catalyze alkene metathesis can be used to promote enyne metathesis.1 Steven T. Diver grew up in Salt Lake City and attended the University of Utah where he studied with Professor F. G. West as an undergraduate researcher. Diver went on to do his doctoral work with Professor Ed Vedejs at the University of WisconsinsMadison, studying nucleophilic catalysis promoted by phosphines. Diver conducted postdoctoral studies with Professor Stuart Schreiber at Harvard where he used alkene metathesis to make chemical dimerizers. Presumably this is where he got bitten by the metathesis bug. Diver began his independent work at the University at Buffalo−The State University of New York (SUNY−Buffalo) in 1997. Diver’s research group is interested in the application of enyne metathesis to challenging synthetic problems, mechanistic aspects of the enyne metathesis, and catalyst design employing unusual heterocyclic carbene ligands.

Removing the Shadow of Suspicion: The Effects of Apology Versus Denial for Repairing Competence- Versus Integrity-Based Trust Violations

Abstract: Two studies were conducted to examine the implications of an apology versus a denial for repairing trust after an alleged violation. Results reveal that trust was repaired more successfully when mistrusted parties (a) apologized for violations concerning matters of competence but denied culpability for violations concerning matters of integrity, and (b) had apologized for violations when there was subsequent evidence of guilt but had denied culpability for violations when there was subsequent evidence of innocence. Supplementary analyses also revealed that the interactive effects of violation type and violation response on participants' trusting intentions were mediated by their trusting beliefs. Combined, these findings provide needed insight and supporting evidence concerning how trust might be repaired in the aftermath of a violation.

Pharmacodynamics of Vancomycin and Other Antimicrobials in Patients with Staphylococcus aureus Lower Respiratory Tract Infections

Abstract: Vancomycin is commonly used to treat staphylococcal infections, but there has not been a definitive analysis of the pharmacokinetics of this antibacterial in relation to minimum inhibitory concentration (MIC) that could be used to determine a target pharmacodynamic index for treatment optimisation. To clarify relationships between vancomycin dosage, serum concentration, MIC and antimicrobial activity by using data gathered from a therapeutic monitoring environment that observes failures in some cases. We investigated all patients with a Staphylococcus aureus lower respiratory tract infection at a 300-bed teaching hospital in the US during a 1-year period. Clinical and pharmacokinetic information was used to determine the following: (i) whether steady-state 24-hour area under the concentration-time curve (AUC24) divided by the MIC (AUC24/MIC) values for vancomycin could be precisely calculated with a software program; (ii) whether the percentage of time vancomycin serum concentrations were above the MIC (%Time>MIC) was an important determinant of vancomycin response; (iii) whether the time to bacterial eradication differed as the AUC24/MIC value increased; (iv) whether the time to bacterial eradication for vancomycin differed compared with other antibacterials at the same AUC24/MIC value; and (v) whether a relationship existed between time to bacterial eradication and time to significant clinical improvement of pneumonia symptoms. The median age of the 108 patients studied was 74 (range 32–93) years. Measured vancomycin AUC24/MIC values were precisely predicted with the A.U.I.C. calculator in a subset of our patients (r2 = 0.935). Clinical and bacteriological response to vancomycin therapy was superior in patients with higher (≥400) AUC24/MIC values (p = 0.0046), but no relationship was identified between vancomycin %Time>MIC and infection response. Bacterial eradication of S. aureus (both methicillin-susceptible and methicillin-resistant) occurred more rapidly (p = 0.0402) with vancomycin when a threshold AUC24/MIC value was reached. S. aureus killing rates were slower with vancomycin than with other antistaphylococcal antibacterials (p = 0.002). There was a significant relationship (p < 0.0001) between time to bacterial eradication and the time to substantial improvement in pneumonia score. Vancomycin AUC24/MIC values predict time-related clinical and bacteriological outcomes for patients with lower respiratory tract infections caused by methicillin-resistant S. aureus.

Mitochondrial α-Ketoglutarate Dehydrogenase Complex Generates Reactive Oxygen Species

Abstract: Mitochondria-produced reactive oxygen species (ROS) are thought to contribute to cell death caused by a multitude of pathological conditions. The molecular sites of mitochondrial ROS production are not well established but are generally thought to be located in complex I and complex III of the electron transport chain. We measured H2O2 production, respiration, and NADPH reduction level in rat brain mitochondria oxidizing a variety of respiratory substrates. Under conditions of maximum respiration induced with either ADP or carbonyl cyanide p-trifluoromethoxyphenylhydrazone,α-ketoglutarate supported the highest rate of H2O2 production. In the absence of ADP or in the presence of rotenone, H2O2 production rates correlated with the reduction level of mitochondrial NADPH with various substrates, with the exception of α-ketoglutarate. Isolated mitochondrial α-ketoglutarate dehydrogenase (KGDHC) and pyruvate dehydrogenase (PDHC) complexes produced superoxide and H2O2. NAD+ inhibited ROS production by the isolated enzymes and by permeabilized mitochondria. We also measured H2O2 production by brain mitochondria isolated from heterozygous knock-out mice deficient in dihydrolipoyl dehydrogenase (Dld). Although this enzyme is a part of both KGDHC and PDHC, there was greater impairment of KGDHC activity in Dld-deficient mitochondria. These mitochondria also produced significantly less H2O2 than mitochondria isolated from their littermate wild-type mice. The data strongly indicate that KGDHC is a primary site of ROS production in normally functioning mitochondria.

Frequent Occurrence of Hypogonadotropic Hypogonadism in Type 2 Diabetes

Abstract: Type 2 diabetes is associated with lower total testosterone (T) levels in cross-sectional studies. However, it is not known whether the defect is primary or secondary. We investigated the prevalence of hypogonadism in type 2 diabetes by measuring serum total T, free T (FT), SHBG, LH, FSH, and prolactin (PRL) in 103 type 2 diabetes patients. FT was measured by equilibrium dialysis. FT was also calculated by using T and SHBG(cFT).HypogonadismwasdefinedaslowFTorcFT.The mean age was 54.7 1.1 yr, mean body mass index (BMI) was 33.4 0.8 kg/m 2 , and mean HbA1c was 8.4 0.2%. The mean T was 12.19 0.50 nmol/liter (351.7 14.4ng/dl), SHBG was 27.89 1.65 nmol/liter, and FT was 0.250 0.014 nmol/liter. Thirty-three percent of patients were hypogonadal. LH and FSH levels were significantly lower in the hypogonadal group compared with patients with normal FT levels (3.15 0.26 vs. 3.91 0.24 mIU/ml for LH and 4.25 0.45 vs. 5.53 0.40 mIU/ml for FSH; P < 0.05). There was a significant inverse correlation ofBMIwithFT(r–0.382;P<0.01)andT(r–0.327;P<0.01). SHBG correlated inversely with BMI (r –0.267; P < 0.05) but positively with age (r 0.538; P < 0.001) and T (r 0.574; P < 0.001). FT correlated strongly with cFT (r 0.919; P < 0.001) but not with SHBG. LH levels correlated positively with FT (r 0.287; P < 0.05). We conclude that hypogonadotropic hypogonadism occurs commonly in type 2 diabetes. (J Clin Endocrinol Metab 89: 5462–5468, 2004)

Circulating Mononuclear Cells in the Obese Are in a Proinflammatory State

Abstract: Background— In view of the increase in plasma concentrations of proinflammatory mediators tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) in obesity, we investigated whether peripheral blood mononuclear cells (MNC) from obese subjects are in a proinflammatory state. Methods and Results— MNC were prepared from fasting blood samples of obese (n=16; body mass index [BMI]=37.7±5.0 kg/m2) and normal-weight control (n=16; BMI=23.8±1.9 kg/m2) subjects. Nuclear factor κB (NF-κB) binding to DNA in nuclear extracts was elevated (P<0.05) and the inhibitor of NFκB-β (IκB-β) was significantly lower (P<0.001) in the obese group. Reverse transcription–polymerase chain reaction revealed elevated levels of migration inhibitor factor (MIF), IL-6, TNF-α, and matrix metalloproteinase-9 (MMP-9) mRNA expression in the obese subjects (P<0.05). Plasma concentrations of MIF, IL-6, TNF-α, MMP-9, and CRP were also significantly higher. Plasma glucose, insulin, and free fatty acids (FFAs) were mea...

Estrogen plus progestin and colorectal cancer in postmenopausal women.

Abstract: background Although the Women’s Health Initiative (WHI) trial of estrogen plus progestin in postmenopausal women identified more overall health risks than benefits among women in the hormone group, the use of estrogen plus progestin was associated with a significant decrease in the risk of colorectal cancer. We analyzed features of the colorectal cancers that developed and their relation to the characteristics of the participants. methods In the WHI trial, 16,608 postmenopausal women who were 50 to 79 years of age and had an intact uterus were randomly assigned to a combination of conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The main outcome measures were the incidence, stages, and types of colorectal cancer, as determined by blinded central adjudication. results There were 43 invasive colorectal cancers in the hormone group and 72 in the placebo group (hazard ratio, 0.56; 95 percent confidence interval, 0.38 to 0.81; P=0.003). The invasive colorectal cancers in the hormone group were similar in histologic features and grade to those in the placebo group but with a greater number of positive lymph nodes (mean ± SD, 3.2 ± 4.1 vs. 0.8 ± 1.7; P=0.002) and were more advanced (regional or metastatic disease, 76.2 percent vs. 48.5 percent; P = 0.004). In exploratory analyses, women in the hormone group with antecedent vaginal bleeding had colorectal cancers with a greater number of positive nodes than women in the hormone group who did not have vaginal bleeding (3.8 ± 4.3 vs. 0.7 ± 1.5 nodes, P=0.006). conclusions Relatively short-term use of estrogen plus progestin was associated with a decreased risk of colorectal cancer. However, colorectal cancers in women who took estrogen plus progestin were diagnosed at a more advanced stage than those in women who took placebo.

Feature selection for text categorization on imbalanced data

Abstract: A number of feature selection metrics have been explored in text categorization, among which information gain (IG), chi-square (CHI), correlation coefficient (CC) and odds ratios (OR) are considered most effective. CC and OR are one-sided metrics while IG and CHI are two-sided. Feature selection using one-sided metrics selects the features most indicative of membership only, while feature selection using two-sided metrics implicitly combines the features most indicative of membership (e.g. positive features) and non-membership (e.g. negative features) by ignoring the signs of features. The former never consider the negative features, which are quite valuable, while the latter cannot ensure the optimal combination of the two kinds of features especially on imbalanced data. In this work, we investigate the usefulness of explicit control of that combination within a proposed feature selection framework. Using multinomial naive Bayes and regularized logistic regression as classifiers, our experiments show both great potential and actual merits of explicitly combining positive and negative features in a nearly optimal fashion according to the imbalanced data.

Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies.

Abstract: Background: Studies in animals have suggested that calcium may reduce the risk of colorectal cancer. However, results from epidemiologic studies of intake of calcium or dairy foods and colorectal cancer risk have been inconclusive. Methods: We pooled the primary data from 10 cohort studies in five countries that assessed usual dietary intake by using a validated food frequency questionnaire at baseline. For most studies, follow-up was extended beyond that in the original publication. The studies included 534 536 individuals, among whom 4992 incident cases of colorectal cancer were diagnosed between 6 and 16 years of follow-up. Pooled multivariable relative risks for categories of milk intake and quintiles of calcium intake and 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided. Results: Milk intake was related to a reduced risk of colorectal cancer. Compared with the lowest category of intake (<70 g/day), relative risks of colorectal cancer for increasing categories (70-174, 175-249, and ≥250 g/day) of milk intake were 0.94 (95% CI = 0.86 to 1.02), 0.88 (95% CI = 0.81 to 0.96), and 0.85 (95% CI = 0.78 to 0.94), respectively (Ptrend <.001). Calcium intake was also inversely related to the risk of colorectal cancer. The relative risk for the highest versus the lowest quintile of intake was 0.86 (95% CI = 0.78 to 0.95; Ptrend = .02) for dietary calcium and 0.78 (95% CI = 0.69 to 0.88; Ptrend <.001) for total calcium (combining dietary and supplemental sources). These results were consistent across studies and sex. The inverse association for milk was limited to cancers of the distal colon (Ptrend <.001) and rectum (Ptrend = .02). Conclusion: Higher consumption of milk and calcium is associated with a lower risk of colorectal cancer. © Oxford University Press 2004, all rights reserved.

Formation and Stability of N-Heterocyclic Carbenes in Water: The Carbon Acid pKa of Imidazolium Cations in Aqueous Solution

Abstract: We report second-order rate constants kDO (M-1 s-1) for exchange for deuterium of the C(2)-proton of a series of simple imidazolium cations to give the corresponding singlet imidazol-2-yl carbenes in D2O at 25 degrees C and I = 1.0 (KCl). Evidence is presented that the reverse protonation of imidazol-2-yl carbenes by solvent water is limited by solvent reorganization and occurs with a rate constant of kHOH = kreorg = 10(11) s-1. The data were used to calculate reliable carbon acid pK(a)s for ionization of imidazolium cations at C(2) to give the corresponding singlet imidazol-2-yl carbenes in water: pKa = 23.8 for the imidazolium cation, pKa = 23.0 for the 1,3-dimethylimidazolium cation, pKa = 21.6 for the 1,3-dimethylbenzimidazolium cation, and pKa = 21.2 for the 1,3-bis-((S)-1-phenylethyl)benzimidazolium cation. The data also provide the thermodynamic driving force for a 1,2-hydrogen shift at a singlet carbene: K12 = 5 x 10(16) for rearrangement of the parent imidazol-2-yl carbene to give neutral imidazole in water at 298 K, which corresponds to a favorable Gibbs free energy change of 23 kcal/mol. We present a simple rationale for the observed substituent effects on the thermodynamic stability of N-heterocyclic carbenes relative to a variety of neutral and cationic derivatives that emphasizes the importance of the choice of reference reaction when assessing the stability of N-heterocyclic carbenes.

Constructing the Spatial Weights Matrix Using a Local Statistic

Abstract: Spatial weights matrices are necessary elements in most regression models where a representation of spatial structure is needed. We construct a spatial weights matrix, W, based on the principle that spatial structure should be considered in a two-part framework, those units that evoke a distance effect, and those that do not. Our two-variable local statistics model (LSM) is based on the G i * local statistic. The local statistic concept depends on the designation of a critical distance, d c , defined as the distance beyond which no discernible increase in clustering of high or low values exists. In a series of simulation experiments LSM is compared to well-known spatial weights matrix specifications – two different contiguity configurations, three different inverse distance formulations, and three semi-variance models. The simulation experiments are carried out on a random spatial pattern and two types of spatial clustering patterns. The LSM performed best according to the Akaike Information Criterion, a spatial autoregressive coefficient evaluation, and Moran’s I tests on residuals. The flexibility inherent in the LSM allows for its favorable performance when compared to the rigidity of the global models.

Enhancements to the behavioral parent training paradigm for families of children with ADHD: review and future directions

Abstract: Behavioral parent training (BPT) is one of the empirically supported psychosocial treatments for ADHD Over many years and in many studies, BPT has been documented to improve both child ADHD behavior and maladaptive parenting behavior In some studies, BPT has also been found to result in benefits in additional domains, such as parenting stress and child classroom behavior However, the BPT literature on children selected as having ADHD lags behind research conducted on BPT for children selected as having oppositional defiant and conduct disorders (ODD and CD, respectively) with regard to examination of factors that may limit treatment attainment, compliance, and outcomes, such as single parenthood, parental psychopathology, and child comorbidity Because of the high degree of comorbidity between ADHD and ODD/CD, it is difficult to separate the two BPT literatures The parameters of BPT (eg format and setting), parent factors, and child factors that may contribute to treatment outcomes for families of children with ADHD are reviewed here and recommendations for future BPT research in the area of ADHD are made

Clinical Spectrum, Morbidity, and Mortality in 113 Pediatric Patients with Mitochondrial Disease

Abstract: Objectives The aim of this study was to elucidate the frequency of major clinical manifestations in children with mitochondrial disease and establish their clinical course, prognosis, and rates of survival depending on their clinical features. Methods We performed a retrospective review of the medical records of 400 patients who were referred for evaluation of mitochondrial disease. By use of the modified Walker criteria, only patients who were assigned a definite diagnosis were included in the study. Results A total of 113 pediatric patients with mitochondrial disease were identified. A total of 102 (90%) patients underwent a muscle biopsy as part of the diagnostic workup. A significant respiratory chain (RC) defect, according to the diagnostic criteria, was found in 71% of the patients who were evaluated. In this cohort, complex I deficiency (32%) and combined complex I, III, and IV deficiencies (26%) were the most common causes of RC defects, followed by complex IV (19%), complex III (16%), and complex II deficiencies (7%). Pathogenic mitochondrial DNA abnormalities were found in 11.5% of the patients. A substantial fraction (40%) of patients with mitochondrial disorders exhibited cardiac disease, diagnosed by Doppler echocardiography; however, the majority (60%) of patients had predominant neuromuscular manifestations. No correlation between the type of RC defect and the clinical presentation was observed. Overall, the mean age at presentation was 40 months. However, the mean age at presentation was 33 months in the cardiac group and 44 months in the noncardiac group. Twenty-six (58%) patients in the cardiac group exhibited hypertrophic cardiomyopathy, 29% had dilated cardiomyopathy, and the remainder (13%) had left ventricular noncompaction. Patients with cardiomyopathy had an 18% survival rate at 16 years of age. Patients with neuromuscular features but no cardiomyopathy had a 95% survival at the same age. Conclusions This study gives strong support to the view that in patients with RC defects, cardiomyopathy is more common than previously thought and tends to follow a different and more severe clinical course. Although with a greater frequency than previously reported, mitochondrial DNA mutations were found in a minority of patients, emphasizing that most mitochondrial disorders of childhood follow a Mendelian pattern of inheritance.

SPICKER: A clustering approach to identify near‐native protein folds

Abstract: We have developed SPICKER, a simple and efficient strategy to identify near-native folds by clustering protein structures generated during computer simulations. In general, the most populated clusters tend to be closer to the native conformation than the lowest energy structures. To assess the generality of the approach, we applied SPICKER to 1489 representative benchmark proteins

Nurses' Perceived Knowledge, Beliefs, Skills, and Needs Regarding Evidence‐Based Practice: Implications for Accelerating the Paradigm Shift

Abstract: Background: The paradigm shift to evidence-based nursing practice in the United States has been slow. Although multiple barriers to evidence-based practice (EBP) have been identified through prior studies, there is a gap in the literature specifically identifying key variables (e.g., belief that EBP produces quality outcomes) that are correlated with the extent to which nurses engage in EBP. Aim: The primary aims of this study were to (1) describe nurses' knowledge, beliefs, skills, and needs regarding EBP; (2) determine whether relationships exist among these variables; and (3) describe major barriers and facilitators to EBP. Methods: A descriptive survey was conducted with a convenience sample of 160 nurses who were attending EBP conferences or workshops in four states located within the Eastern Region of the United States. Results: Although participant beliefs about the benefit of EBP were high, knowledge of EBP was relatively low. Significant relationships were found between the extent to which the nurses' practice is evidence-based and (1) nurses' knowledge of EBP, (2) nurses' beliefs about the benefits of EBP, (3) having an EBP mentor, and (4) using the Cochrane Database of Systematic Reviews and the National Guideline Clearinghouse. Conclusion and Implications: Health care systems need to implement interventions that not only increase nurses' EBP knowledge and skills, but also strengthen their beliefs about the benefit of evidence-based care. EBP mentors may be key in accelerating a more rapid shift toward evidence-based nursing practice. Theoretically driven randomized controlled trials are urgently needed to test the effectiveness of interventions on advancing evidence-based care.

Water-Soluble Poly(acrylic acid) Grafted Luminescent Silicon Nanoparticles and Their Use as Fluorescent Biological Staining Labels

Abstract: UV-induced graft polymerization of acrylic acid (AAc) on the surface of silicon nanoparticles was used to prepare a stable aqueous luminescent silicon nanoparticle solution. By grafting a water-soluble polymer on the particle surface, the dispersions in water of the silicon nanoparticles became very stable and clear aqueous solutions could be obtained. XPS and NMR spectroscopy confirmed that PAAc was covalently grafted to the silicon nanoparticles. The grafted PAAc on silicon particles increased not only the dispersibility but also improved the photoluminescence stability of the silicon nanoparticles against degradation by water. The surface-modified nanoparticles were used as biological labels for cell imaging. The Si quantum dot labels exihibited bright fluorescence images and provided higher resistance to photobleaching than the commonly used organic dyes.

Evidence for a potent antiinflammatory effect of rosiglitazone.

Abstract: We have recently demonstrated a potent antiinflammatory effect of troglitazone, an agonist of peroxisome proliferator-activated receptor γ (PPARγ) and a partial agonist of PPARα in both the nondiabetic obese and diabetic obese subjects. We have now investigated the antiinflammatory actions of rosiglitazone, a selective PPARγ agonist. Eleven nondiabetic obese subjects and 11 obese diabetic subjects were each given 4 mg of rosiglitazone daily for a period of 6 wk. Fasting blood samples were obtained at 0, 1, 2, 4, 6, and 12 wk (6 wk after the cessation of rosiglitazone). Eight obese subjects and five obese diabetic subjects were also included in the study as control groups. Fasting blood samples were obtained from the control groups at 0, 1, 2, 4, and 6 wk only. Nuclear factor κB (NFκB)-binding activity in mononuclear cells, plasma monocyte chemoattractant protein-1 (MCP-1), TNF-α, soluble intercellular adhesion molecule-1, C-reactive protein (CRP), and serum amyloid A (SAA) were measured. Blood glucose con...

Near-fault ground motions, and the response of elastic and inelastic single-degree-of-freedom (SDOF) systems

Abstract: SUMMARY In order to investigate the response of structures to near-fault seismic excitations, the ground motion input should be properly characterized and parameterized in terms of simple, yet accurate and reliable, mathematical models whose input parameters have a clear physical interpretation and scale, to the extent possible, with earthquake magnitude. Such a mathematical model for the representation of the coherent (long-period) ground motion components has been proposed by the authors in a previous study and is being exploited in this article for the investigation of the elastic and inelastic response of the single-degree-of-freedom (SDOF) system to near-fault seismic excitations. A parametric analysis of the dynamic response of the SDOF system as a function of the input parameters of the mathematical model

Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial.

Abstract: Background. Infants developing bronchopulmonary dysplasia (BPD) show decreased cortisol response to adrenocorticotropic hormone. A pilot study of low-dose hydrocortisone therapy for prophylaxis of early adrenal insufficiency showed improved survival without BPD at 36 weeks’ postmenstrual age, particularly in infants exposed to histologic chorioamnionitis. Methods. Mechanically ventilated infants with birth weights of 500 to 999 g were enrolled into this multicenter, randomized, masked trial between 12 and 48 hours of life. Patients received placebo or hydrocortisone, 1 mg/kg per day for 12 days, then 0.5 mg/kg per day for 3 days. BPD at 36 weeks’ postmenstrual age was defined clinically (receiving supplemental oxygen) and physiologically (supplemental oxygen required for O2 saturation ≥90%). Results. Patient enrollment was stopped at 360 patients because of an increase in spontaneous gastrointestinal perforation in the hydrocortisone-treated group. Survival without BPD was similar, defined clinically or physiologically, as were mortality, head circumference, and weight at 36 weeks. For patients exposed to histologic chorioamnionitis (n = 149), hydrocortisone treatment significantly decreased mortality and increased survival without BPD, defined clinically or physiologically. After treatment, cortisol values and response to adrenocorticotropic hormone were similar between groups. Hydrocortisone-treated infants receiving indomethacin had more gastrointestinal perforations than placebo-treated infants receiving indomethacin, suggesting an interactive effect. Conclusions. Prophylaxis of early adrenal insufficiency did not improve survival without BPD in the overall study population; however, treatment of chorioamnionitis-exposed infants significantly decreased mortality and improved survival without BPD. Low-dose hydrocortisone therapy did not suppress adrenal function or compromise short-term growth. The combination of indomethacin and hydrocortisone should be avoided.

Prediction of Neuropsychological Impairment in Multiple Sclerosis Comparison of Conventional Magnetic Resonance Imaging Measures of Atrophy and Lesion Burden

Abstract: Background Cognition and magnetic resonance imaging correlations are well established in patients with multiple sclerosis (MS), but it is unclear whether lesion burden or atrophy accounts for most of the predictive variance. These indices have been directly compared in only a few studies. No such study included measurement of the third ventricle, which was strongly predictive of neuropsychological competence in the early literature. Furthermore, few studies accounted for the influence of age, premorbid intelligence, or depression. Objective To determine if conventional measures of lesion burden or atrophy predict cognitive dysfunction in MS while accounting for age, premorbid intelligence, and depression. Methods We studied 37 patients with MS and 27 controls matched according to demographic variables. Correlations between neuropsychological tests and the following magnetic resonance imaging indices were considered: T1 hypointense lesion volume, fluid-attenuated inversion recovery hyperintense lesion volume, third ventricle width, bicaudate ratio, and brain parenchymal fraction. Regression models predicting neuropsychological performance controlled for the effects of age, premorbid intelligence, and depression. We included only those tests discriminating patients with MS from controls. Results In each regression model, third ventricle width was the sole magnetic resonance imaging measure retained. When this variable was removed from consideration, brain parenchymal fraction was retained in all analyses. Conclusions Brain atrophy accounts for more variance than lesion burden in predicting cognitive impairment in MS, and central atrophy in particular is strongly associated with neuropsychological morbidity. This finding may be explained in part by atrophy of the thalamus, a deep gray matter structure that mediates cognitive function via cortical and subcortical pathways. Enthusiasm for the clinical utility of third ventricle width is tempered by modest intraobserver and interobserver reliability.

Automated structure prediction of weakly homologous proteins on a genomic scale

Abstract: We have developed TASSER, a hierarchical approach to protein structure prediction that consists of template identification by threading, followed by tertiary structure assembly via the rearrangement of continuous template fragments guided by an optimized C(alpha) and side-chain-based potential driven by threading-based, predicted tertiary restraints. TASSER was applied to a comprehensive benchmark set of 1,489 medium-sized proteins in the Protein Data Bank. With homologues excluded, in 927 cases, the templates identified by our threading algorithm PROSPECTOR_3 have a rms deviation from native <6.5 A with approximately 80% alignment coverage. After template reassembly, this number increases to 1,172. This shows significant and systematic improvement of the final models with respect to the initial template alignments. Furthermore, significant improvements in loop modeling are demonstrated. We then apply TASSER to the 1,360 medium-sized ORFs in the Escherichia coli genome; approximately 920 can be predicted with high accuracy based on confidence criteria established in the Protein Data Bank benchmark. These results from our unprecedented comprehensive folding benchmark on all protein categories provide a reliable basis for the application of TASSER to structural genomics, especially to proteins of low sequence identity to solved protein structures.

Offline signature verification and identification using distance statistics

Abstract: This paper describes a novel approach for signature verification and identification in an offline environment based on a quasi-multiresolution technique using GSC (Gradient, Structural and Concavity) features for feature extraction. These features when used at the word level, instead of the character level, yield promising results with accuracies as high as 78% and 93% for verification and identification, respectively. This method was successfully employed in our previous theory of individuality of handwriting developed at CEDAR — based on obtaining within and between writer statistical distance distributions. In this paper, exploring signature verification and identification as offline handwriting verification and identification tasks respectively, we depict a mapping from the handwriting domain to the signature domain.

Self-administration and interviewer-administration of the German Chronic Respiratory Questionnaire: instrument development and assessment of validity and reliability in two randomised studies

Abstract: Assessment of health-related quality of life (HRQL) is important in patients with chronic obstructive pulmonary disease (COPD). Despite the high prevalence of COPD in Germany, Switzerland and Austria there is no validated disease-specific instrument available. The objective of this study was to translate the Chronic Respiratory Questionnaire (CRQ), one of the most widely used respiratory HRQL questionnaires, into German, develop an interviewer- and self-administered version including both standardised and individualised dyspnoea questions, and validate these versions in two randomised studies. We recruited three groups of patients with COPD in Switzerland, Germany and Austria. The 44 patients of the first group completed the CRQ during pilot testing to adapt the CRQ to German-speaking patients. We then recruited 80 patients participating in pulmonary rehabilitation programs to assess internal consistency reliability and cross-sectional validity of the CRQ. The third group consisted of 38 patients with stable COPD without an intervention to assess test-retest reliability. To compare the interviewer- and self-administered versions, we randomised patients in groups 2 and 3 to the interviewer- or self-administered CRQ. Patients completed both the standardised and individualised dyspnoea questions. For both administration formats and all domains, we found good internal consistency reliability (Crohnbach's alpha between 0.73 and 0.89). Cross-sectional validity tended to be better for the standardised compared to the individualised dyspnoea questions and cross-sectional validity was slightly better for the self-administered format. Test-retest reliability was good for both the interviewer-administered CRQ (intraclass correlation coefficients for different domains between 0.81 and 0.95) and the self-administered format (intraclass correlation coefficients between 0.78 and 0.86). Lower within-person variability was responsible for the higher test-retest reliability of the interviewer-administered format while between person variability was similar for both formats. Investigators in German-speaking countries can choose between valid and reliable self-and interviewer-administered CRQ formats.