bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expected value of information and decision making in HTA
Authors: Eckermann Simon , Willan Andrew R. 
Published: September 2006

AbstractDecision makers within a jurisdiction facing evidence of positive but uncertain incremental net benefit of a new health care intervention have viable options where no further evidence is anticipated to:
adopt the new intervention without further evidence;
adopt the new intervention and undertake a trial; or
delay the decision and undertake a trial.
Value of information methods have been shown previously to allow optimal design of clinical trials in comparing option (2) against option (1), by trading off the expected value and cost of sample information. However, this previous research has not considered the effect of cost of reversal on expected value of information in comparing these options. This paper demonstrates that, where a new intervention is adopted, the expected value of information is reduced under optimal decision making with costs of reversing decisions. Further, the paper shows that comparing expected net gain of optimally designed trials for option (2) vs (1) conditional on cost of reversal, and (3) vs (1) conditional on opportunity cost of delay allow systematic identification of an optimal decision strategy and trial design. Copyright © 2006 John Wiley & Sons, Ltd.
Elasticities of market shares and social health insurance choice in germany: a dynamic panel data approach
Authors: Tamm Marcus , Tauchmann Harald , Wasem Jürgen , Greß Stefan 
Published: September 2006

AbstractIn 1996, free choice of health insurers was introduced to the German social health insurance system. One objective was to increase efficiency through competition. A crucial precondition for effective competition among health insurers is that consumers search for lower‐priced health insurers. We test this hypothesis by estimating the price elasticities of insurers' market shares. We use unique panel data and specify a dynamic panel model to explain changes in market shares. Estimation results suggest that short‐run price elasticities are smaller than previously found by other studies. In the long‐run, however, estimation results suggest substantial price effects. Copyright © 2006 John Wiley & Sons, Ltd.
Are low ultraviolet B and high animal protein intake associated with risk of renal cancer?
Authors: Mohr Sharif B. , Gorham Edward D. , Garland Cedric F. , Grant William B. , Garland Frank C. 
Published: September 2006

AbstractIncidence rates of kidney cancer are thought to be highest in places situated at high latitudes and in populations with high intake of energy from animal sources. This suggests that low 25‐hydroxyvitamin D status, due to lower levels of UVB irradiance, and energy from animal sources might be involved in etiology. The association of latitude with age‐adjusted incidence rates was determined for all 175 countries in a UN cancer database, GLOBOCAN. The independent association of UVB irradiance, cloud cover and intake of calories from animal sources with age‐adjusted incidence rates was assessed using multiple regression in 139 countries that provided dietary data. Renal cancer incidence rates were highest in countries situated at the highest latitudes, in men (R2 = 0.64, p < 0.01) and women (R2 = 0.63, p < 0.01). According to multivariate analysis in men, UVB irradiance was inversely associated with renal cancer incidence rates (p = 0.0003), while cloud cover (p = 0.003) and intake of calories from animal sources (p < 0.0001) were independently positively associated (R2 for model = 0.73, p < 0.0001). In women, UVB irradiance was inversely associated with incidence rates (p = 0.04), while total cloud cover (p = 0.0008) and calories from animal sources (p < 0.0001) were positively associated (R2 = 0.68, p < 0.0001). Lower levels of UVB irradiance and higher intakes of calories from animal sources were independently associated with higher incidence rates of kidney cancer. © 2006 Wiley‐Liss, Inc.
APC gene methylation is inversely correlated with features of the CpG island methylator phenotype in colorectal cancer
Authors: Iacopetta Barry , Grieu Fabienne , Li Wei , Ruszkiewicz Andrew , Caruso Maria , Moore James , Watanabe Goh , Kawakami Kazuyuki 
Published: September 2006

AbstractThe notion of a CpG island methylator phenotype (CIMP) was proposed to describe a subset of colorectal cancers (CRC) displaying frequent and concordant methylation of CpG islands located within gene promoter regions. Some workers have failed to observe associations between CIMP and specific clinicopathological features of CRC, possibly because of the choice of genes used to define this phenotype. The aim of the current study was to determine whether the aberrant methylation of 6 genes implicated in CRC development was associated with the same phenotypic features of this tumour type. The MethyLight assay was used to provide quantitative estimates of MLH1, P16, TIMP3, P14, DAPK and APC methylation levels in 199 unselected colorectal tumours. The methylation of MLH1, P16, TIMP3 and P14 was highly concordant (p < 0.0001 for each pair) but that of DAPK and APC was not. An inverse association was observed between the methylation of APC and TIMP3 (p = 0.004). Methylation of the MLH1, P16, TIMP3 and P14 genes was associated with tumour infiltrating lymphocytes (p < 0.05), microsatellite instability (p < 0.001), BRAF mutation (p < 0.0001) and elevated concentrations of the methyl group carriers tetrahydrofolate (THF) and 5,10‐methylene THF (p < 0.05). In contrast, APC methylation was associated with wildtype BRAF (p = 0.003) and with lower concentrations of methyl group carriers (p < 0.05). These findings highlight the importance of gene selection in studies that aim to characterize the biological features and clinical behaviour of CIMP+ tumours. © 2006 Wiley‐Liss, Inc.
The late Quaternary tephrostratigraphical record of the San Gregorio Magno basin (southern Italy)
Authors: Munno R. , Petrosino P. 
Published: September 2006

AbstractTwenty‐one primary pyroclastic layers were found embedded in the lacustrine sediments of the San Gregorio Magno basin (Southern Apennines). These sand‐sized layers were characterised by a noticeable juvenile fragments content and by a sharp basal contact with the underlying clay and silt sediments. The tephra layers have been correlated with terrestrial counterparts from well‐known eruptive events of the Campanian volcanic area, or with reference layers from deep sea sediment cores and from the Monticchio maar sequence. The investigation of the San Gregorio Magno tephra layers made it possible to deduce that lacustrine sedimentation at San Gregorio Magno basin began before 170k yr BP and lasted at least until the emplacement of the Neapolitan Yellow Tuff, which occurred about 15k yr BP. The tephrochronology allowed determination of the varying sedimentation rate that occurred in the basin. Correlation of the lacustrine record with marine sequences has allowed development of a late Quaternary tephrostratotype for southern Italy. Copyright © 2006 John Wiley & Sons, Ltd.
Discrepancies in the characterization of the glass transition in thin films of hyperbranched polyesters
Authors: Serghei A. , Mikhailova Y. , Eichhorn K.‐J. , Voit B. , Kremer F. 
Published: September 2006

AbstractThe dynamic glass transition and the dilatometric glass transition temperature are simultaneously characterized in thin films of hyperbranched aromatic polyesters by broadband dielectric spectroscopy and capacitive scanning dilatometry. A diverging thickness dependence is detected: while the temperature position of the alpha relaxation peak Tα decreases by ∼30 K, the dilatometric Tg increases by ∼10 K with decreasing film thickness. This emphasizes the subtle character of the glass transition phenomenon—as manifested in the molecular dynamics and in the (structural) thermal expansion—and proves that, in contrast to the bulk, different experimental techniques do not necessarily deliver similar results in confinement. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 3006–3010, 2006
Comparison of multiple Amber force fields and development of improved protein backbone parameters
Authors: Hornak Viktor , Abel Robert , Okur Asim , Strockbine Bentley , Roitberg Adrian , Simmerling Carlos 
Published: September 2006

AbstractThe ff94 force field that is commonly associated with the Amber simulation package is one of the most widely used parameter sets for biomolecular simulation. After a decade of extensive use and testing, limitations in this force field, such as over‐stabilization of α‐helices, were reported by us and other researchers. This led to a number of attempts to improve these parameters, resulting in a variety of “Amber” force fields and significant difficulty in determining which should be used for a particular application. We show that several of these continue to suffer from inadequate balance between different secondary structure elements. In addition, the approach used in most of these studies neglected to account for the existence in Amber of two sets of backbone φ/ψ dihedral terms. This led to parameter sets that provide unreasonable conformational preferences for glycine. We report here an effort to improve the φ/ψ dihedral terms in the ff99 energy function. Dihedral term parameters are based on fitting the energies of multiple conformations of glycine and alanine tetrapeptides from high level ab initio quantum mechanical calculations. The new parameters for backbone dihedrals replace those in the existing ff99 force field. This parameter set, which we denote ff99SB, achieves a better balance of secondary structure elements as judged by improved distribution of backbone dihedrals for glycine and alanine with respect to PDB survey data. It also accomplishes improved agreement with published experimental data for conformational preferences of short alanine peptides and better accord with experimental NMR relaxation data of test protein systems. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Stereochemistry of guanidine–metal interactions: Implications for L‐arginine–metal interactions in protein structure and function
Authors: Di Costanzo Luigi , Flores Lloyd V. , Christianson David W. 
Published: September 2006

AbstractThe geometries of 150 guanidine–metal ion interactions retrieved from crystal structures deposited in the Cambridge Structural Database have been analyzed. Metal ions exhibit a preference for anti coordination stereochemistry in the plane of the unprotonated guanidine group, usually in chelate complexes with a diguanidine moiety, but syn‐oriented interactions are occasionally found for single guanidine–metal interactions. Three L‐arginine‐metal coordination interactions are found in metalloenzyme structures deposited in the Protein Data Bank: biotin synthase from E. coli, His‐67 → Arg human carbonic anhydrase I, and inactivated B. caldovelox arginase complexed with L‐arginine. In these proteins, L‐arginine‐metal coordination adopts syn/out‐of‐plane and anti/in‐plane coordination stereochemistry. The implications of these results for L‐arginine‐metal interactions in protein structure and function are discussed. Although such interactions are rare, this analysis serves as a useful reference point for the growing interest in enzymes containing L‐arginine residues that function as general bases or metal ligands. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Prediction of EF‐hand calcium‐binding proteins and analysis of bacterial EF‐hand proteins
Authors: Zhou Yubin , Yang Wei , Kirberger Michael , Lee Hsiau‐Wei , Ayalasomayajula Gayatri , Yang Jenny J. 
Published: September 2006

AbstractThe EF‐hand protein with a helix–loop–helix Ca2+ binding motif constitutes one of the largest protein families and is involved in numerous biological processes. To facilitate the understanding of the role of Ca2+ in biological systems using genomic information, we report, herein, our improvement on the pattern search method for the identification of EF‐hand and EF‐like Ca2+‐binding proteins. The canonical EF‐hand patterns are modified to cater to different flanking structural elements. In addition, on the basis of the conserved sequence of both the N‐ and C‐terminal EF‐hands within S100 and S100‐like proteins, a new signature profile has been established to allow for the identification of pseudo EF‐hand and S100 proteins from genomic information. The new patterns have a positive predictive value of 99% and a sensitivity of 96% for pseudo EF‐hands. Furthermore, using the developed patterns, we have identified zero pseudo EF‐hand motif and 467 canonical EF‐hand Ca2+ binding motifs with diverse cellular functions in the bacteria genome. The prediction results imply that pseudo EF‐hand motifs are phylogenetically younger than canonical EF‐hand motifs. Our prediction of Ca2+ binding motifs provides not only an insight into the role of Ca2+ and Ca2+‐binding proteins in bacterial systems, but also a way to explore and define the role of Ca2+ in other biological systems (calciomics). Proteins 2006. © 2006 Wiley‐Liss, Inc.
Molecular dynamics simulations of Hydrogenobacter thermophilus cytochrome c552: Comparisons of the wild‐type protein, a b‐type variant, and the apo state
Authors: Smith Lorna J. , Davies Robert J. , van Gunsteren Wilfred F. 
Published: September 2006

AbstractMolecular dynamic simulations have been performed for wild‐type Hydrogenobacter thermophilus cytochrome c552, a b‐type variant of the protein, and the apo state with the heme prosthetic group removed. In the b‐type variant, Cys 10 and Cys 13 were mutated to alanine residues, and so the heme group was no longer covalently bound to the protein. Two 8‐ns simulations have been performed for each system at 298 and 360 K. The simulations of the wild‐type protein at 298 K show a very close agreement with experimental NMR data. A fluxional process involving the side chain of Met 59, which coordinates to the heme iron, is observed in accord with proposals from NMR studies. Overall, the structure and dynamical behavior of the protein during the simulations of the b‐type variant is closely similar to that of the wild‐type protein. However, side chains in the heme‐binding site show larger fluctuations in the b‐type variant simulation at 360 K. In addition, structural changes are seen for a number of residues close to the heme group, particularly Gly 22 and Ser 51. The simulations of the apo state show significant conformational changes for residues 50–59. These residues form a loop region, which packs over the heme group in the wild‐type protein and hydrogen bonds to the heme propionate groups. In the absence of heme, in the apo state simulations, these residues form short but persistent regions of β‐sheet secondary structure. These could provide nucleation sites for the conversion to amyloid fibrils. Proteins 2006. © 2006 Wiley‐Liss, Inc.
A novel high resolution CαCα distance dependent force field based on a high quality decoy set
Authors: Rajgaria R. , McAllister S. R. , Floudas C. A. 
Published: September 2006

AbstractThis work presents a novel CαCα distance dependent force field which is successful in selecting native structures from an ensemble of high resolution near‐native conformers. An enhanced and diverse protein set, along with an improved decoy generation technique, contributes to the effectiveness of this potential. High quality decoys were generated for 1489 nonhomologous proteins and used to train an optimization based linear programming formulation. The goal in developing a set of high resolution decoys was to develop a simple, distance‐dependent force field that yields the native structure as the lowest energy structure and assigns higher energies to decoy structures that are quite similar as well as those that are less similar. The model also includes a set of physical constraints that were based on experimentally observed physical behavior of the amino acids. The force field was tested on two sets of test decoys not in the training set and was found to excel on all the metrics that are widely used to measure the effectiveness of a force field. The high resolution force field was successful in correctly identifying 113 native structures out of 150 test cases and the average rank obtained for this test was 1.87. All the high resolution structures (training and testing) used for this work are available online and can be downloaded from http://titan.princeton.edu/HRDecoys. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Aggregation of small peptides studied by molecular dynamics simulations
Authors: Flöck Dagmar , Rossetti Giulia , Daidone Isabella , Amadei Andrea , Nola Alfredo Di 
Published: September 2006

AbstractPeptides and proteins tend to aggregate under appropriate conditions. The amyloid fibrils that are ubiquitously found among these structures are associated with major human diseases like Alzheimer's disease, type II diabetes, and various prion diseases. Lately, it has been observed that even very short peptides like tetra and pentapeptides can form ordered amyloid structures. Here, we present aggregation studies of three such small polypeptide systems, namely, the two amyloidogenic peptides DFNKF and FF, and a control (nonamyloidogenic) one, the AGAIL. The respective aggregation process is studied by all‐atom Molecular Dynamics simulations, which allow to shed light on the fine details of the association and aggregation process. Our analysis suggests that naturally aggregating systems exhibit significantly diverse overall cluster shape properties and specific intermolecular interactions. Additional analysis was also performed on the previously studied NFGAIL system. Proteins 2006. © 2006 Wiley‐Liss, Inc.
QSAR Study of Aromatic Organochalcogens with Glutathione Peroxidase – like Antioxidant Activity
Authors: Nikolic Katarina M. 
Published: September 2006

AbstractThe molecular orbital energies and atomic Electron Densities (ED) of compounds that mimic the action of Glutathione Peroxidase (GPx), such as derivatives of α‐(phenylselenenyl) keton (PhSeR1) and aromatic organochalcogens [YPh(X)1–2PhY], were calculated by ab initio Hartree‐Fock/3‐21G (d)gas basis set. Single and multiple linear regression models for two types of aromatic chalcogens were obtained with R2>0.75 and $\rm{ q_{{\rm{pre}}}^2 }$>0.63. For the α‐(phenylselenenyl) keton and derivatives that react with Glutathione (GSH) via mixed selenenyl‐sulfide compounds (RSeSG), a high correlation was obtained between the calculated LUMO (PhSeR1) energies and experimentally measured GPx like antioxidant activities. Thus, it is recommended to use the LUMO (PhSeR1) energies of novel derivatives (PhSeR1) of α‐(phenylselenenyl) keton in the prediction of GPx like catalytic antioxidant activities. For the aromatic organochalcogens [YPh(X)1–2PhY] that react with GSH mainly via chalcogen‐oxide intermediates, the Electrochemical Oxidation Potential (Epa) values on the glassy carbon electrode in aqueous media, the HOMO [YPh(X)1–2PhY] energies, and the ED on chalcogens [ED(X)] were selected as good predictors of GPx like catalytic antioxidant activities.
Neural Network Based QSPR Study for Predicting pKa of Phenols in Different Solvents
Authors: Jover Jesús , Bosque Ramón , Sales Joaquim 
Published: September 2006

AbstractComputational Neural Network (CNN) based QSPR methodology is applied to a multicomponent system: the prediction of pKa of phenols in different solvents. The system is composed of 94 phenols, 10 solvents, and 276 experimental pKa values. The phenols are characterized by the habitual molecular descriptors, while the solvents are described by a number of physical properties and by several parameters of the most used multiparametric polarity solvent scales. The proposed model, non‐linearly derived, contains seven descriptors; five of them belong to the solutes and the other two to the solvents. Good results are obtained with a Root‐Mean‐Square Error (RMSE) and correlation coefficients (R2) of 0.71 (0.982), 0.83 (0.977), and 0.95 (0.975) for the training, prediction, and cross validation sets, respectively. The robustness of the model is also in accord with the statistical results obtained from particular subsets of phenols with and without ortho‐substituents and those obtained from the subsets of values of pKa determined in protic or in aprotic solvents and also in each solvent. The descriptors of the model encode information that reflects characteristics of the molecules of the solutes and the solvents clearly related to the interactions acting in the dissociation process.
A comparison of adaptive allocation rules for group‐sequential binary response clinical trials
Authors: Morgan Caroline C. , Stephen Coad D. 
Published: September 2006

AbstractIn clinical trials to compare two or more treatments with dichotomous responses, group‐sequential designs may reduce the total number of patients involved in the trial and response‐adaptive designs may result in fewer patients being assigned to the inferior treatments. In this paper, we combine group‐sequential and response‐adaptive designs, extending recent work on sample size re‐estimation in trials to compare two treatments with normally distributed responses, to analogous binary response trials. We consider the use of two parameters of interest in the group‐sequential design, the log odds ratio and the simple difference between the probabilities of success. In terms of the adaptive sampling rules, we study two urn models, the drop‐the‐loser rule and the randomized Pólya urn rule, and compare their properties with those of two sequential maximum likelihood estimation rules, which minimize the expected number of treatment failures. We investigate two ways in which adaptive urn designs can be used in conjunction with group‐sequential designs. The first method updates the urn at each interim analysis and the second method continually updates the urn after each patient response, assuming immediate patient responses. Our simulation results show that the group‐sequential design, which uses the drop‐the‐loser rule, applied fully sequentially, is the most effective method for reducing the expected number of treatment failures and the average sample number, whilst still maintaining the nominal error rates, over a range of success probabilities. Copyright © 2006 John Wiley & Sons, Ltd.
Quantifying the treatment effect explained by markers in the presence of measurement error
Authors: Sarkar Somnath , Qu Yongming 
Published: September 2006

AbstractSurrogate markers or intermediate markers are important in identifying subjects with high risk of a serious disease or for monitoring disease progression of a subject on treatment. Quantifying the proportion of treatment effect (PTE) explained by markers has been studied extensively. Due to reasons such as biological variation, limited machine precision, etc. markers are generally measured with error. The estimated PTE ignoring the measurement error could be biased, which may lead to incorrect conclusions. In this article, we adjust for the measurement error using regression calibration to construct a less biased estimator of excess relative odds, a quantity to measure the treatment effect explained by markers. The method is applied to data from a clinical study in osteoporosis. Copyright © 2006 John Wiley & Sons, Ltd.