bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two‐stage randomization designs in drug development
Authors: Wolbers Marcel , Helterbrand Jeffrey D. 
Published: June 2008

AbstractOne challenge in oncology drug development is to determine whether a new agent to the care of patients should be added concurrently as a new component to standard of care (SOC) induction treatment, used sequentially as an extended maintenance treatment after SOC induction for patients responding to induction therapy, or used in both the induction and the maintenance settings. A two‐stage randomization design (TSRD) addresses these questions simultaneously. In such trials patients are initially randomized to two induction therapies, followed by another randomization to maintenance therapy contingent upon disease remission under induction therapy. We survey recently proposed methods for analyzing time‐to‐event endpoints in TSRDs and discuss several issues related to the use of TSRDs including sample size calculation and multiplicity.An alternative drug development strategy is to perform several single randomization designs (SRDs) comparing induction and maintenance regimens, respectively. We present a simulation study, which compares TSRDs to several strategies based on SRDs in terms of total sample size and time to reach clinical decisions. Copyright © 2008 John Wiley & Sons, Ltd.
Estimating a weighted average of stratum‐specific parameters
Authors: Brumback Babette A. , Winner Larry H. , Casella George , Ghosh Malay , Hall Allyson , Zhang Jianyi , Chorba Lorna , Duncan Paul 
Published: June 2008

AbstractThis article investigates estimators of a weighted average of stratum‐specific univariate parameters and compares them in terms of a design‐based estimate of mean‐squared error (MSE). The research is motivated by a stratified survey sample of Florida Medicaid beneficiaries, in which the parameters are population stratum means and the weights are known and determined by the population sampling frame. Assuming heterogeneous parameters, it is common to estimate the weighted average with the weighted sum of sample stratum means; under homogeneity, one ignores the known weights in favor of precision weighting. Adaptive estimators arise from random effects models for the parameters. We propose adaptive estimators motivated from these random effects models, but we compare their design‐based performance. We further propose selecting the tuning parameter to minimize a design‐based estimate of mean‐squared error. This differs from the model‐based approach of selecting the tuning parameter to accurately represent the heterogeneity of stratum means. Our design‐based approach effectively downweights strata with small weights in the assessment of homogeneity, which can lead to a smaller MSE. We compare the standard random effects model with identically distributed parameters to a novel alternative, which models the variances of the parameters as inversely proportional to the known weights. We also present theoretical and computational details for estimators based on a general class of random effects models. The methods are applied to estimate average satisfaction with health plan and care among Florida beneficiaries just prior to Medicaid reform. Copyright © 2008 John Wiley & Sons, Ltd.
Comparison of two‐phase analyses for case–control genetic association studies
Authors: Zheng Gang , Meyer Mark , Li Wentian , Yang Yaning 
Published: June 2008

AbstractTo test for genetic association between a marker and a complex disease using a case–control design, Cochran–Armitage trend tests (CATTs) and Pearson's chi‐square test are often employed. Both tests are genotype‐based. Song and Elston (Statist. Med. 2006; 25:105–126) introduced the Hardy–Weinberg disequilibrium trend test and combined it with CATT to test for association. Compared to using a single statistic to test for case–control genetic association (referred to as single‐phase analysis), two‐phase analysis is a new strategy in that it employs two test statistics in one analysis framework, each statistic using all available case–control data. Two such two‐phase analysis procedures were studied, in which Hardy–Weinberg equilibrium (HWE) in the population is a key assumption, although the procedures are robust to moderate departure from HWE. Our goal in this article is to study a new two‐phase procedure and compare all three two‐phase analyses and common single‐phase procedures by extensive simulation studies. For illustration, the results are applied to real data from two case–control studies. On the basis of the results, we conclude that with an appropriate choice of significance level for the analysis in phase 1, some two‐phase analyses could be more powerful than commonly used test statistics. Copyright © 2008 John Wiley & Sons, Ltd.
Genotype‐adjusted familial correlation analysis using three generalized estimating equations
Authors: Lee Hye‐Seung , Paik Myunghee Cho , Lee Joseph H. 
Published: June 2008

AbstractWe analyze familial correlation of a memory score from Caribbean Hispanic families that have multiple family members affected with Alzheimer's disease, adjusting for having at least one APOE‐ε4 allele, as well as other confounders. To enhance the efficiency of correlation model, this paper proposes an alternative approach for three generalized estimating equations proposed by Yan and Fine (Statist. Med. 2004; 23:859–874). The efficiency of correlation model is evaluated through the asymptotic relative efficiency computation and simulations. Copyright © 2008 John Wiley & Sons, Ltd.
The assessment of non‐inferiority in a gold standard design with censored, exponentially distributed endpoints
Authors: Mielke Matthias , Munk A. , Schacht A. 
Published: June 2008

AbstractThe objective of this paper is to develop statistical methodology for non‐inferiority hypotheses to censored, exponentially distributed time to event endpoints. Motivated by a recent clinical trial in depression, we consider a gold standard design where a test group is compared with an active reference and with a placebo group. The test problem is formulated in terms of a retention of effect hypothesis. Thus, the proposed Wald‐type test procedure assures that the effect of the test group is better than a pre‐specified proportion Δ of the treatment effect of the reference group compared with the placebo group. A sample size allocation rule to achieve optimal power is presented, which only depends on the pre‐specified Δ and the probabilities for the occurrence of censoring. In addition, a pretest is presented for either the reference or the test group to ensure assay sensitivity in the complete test procedure. The actual type I error and the sample size formula of the proposed tests are explored asymptotically by means of a simulation study showing good small sample characteristics. To illustrate the procedure a randomized, double blind clinical trial in depression is evaluated. An R‐package for implementation of the proposed tests and for sample size determination accompanies this paper on the author's web page. Copyright © 2008 John Wiley & Sons, Ltd.
Tumor‐Inhibitory Effect and Immunomodulatory Activity of Fullerol C60(OH)x
Authors: Zhu Jiadan , Ji Zhiqiang , Wang Jing , Sun Ronghua , Zhang Xiang , Gao Yang , Sun Hongfang , Liu Yuanfang , Wang Zheng , Li Aidong , Ma Jie , Wang Tiancheng , Jia Guang , Gu Yiqun 
Published: June 2008

AbstractThe tumor‐inhibitory effect of C60(OH)x was tested on the murine H22 hepatocarcinoma model. Doses of 0.2 and 1.0 mg kg−1 body weight both showed significant antitumor activity with tumor inhibition rates of 31.9 and 38.4%, respectively, when mice were treated for 17 consecutive days. The damnification of liver was prominently reduced. Furthermore, histological examination indicated that an envelope of fibroblasts and lymphocytes was formed surrounding tumor tissues in the C60(OH)x‐treated group, which inhibited the infiltration of tumor to the neighboring normal skeleton muscle tissues. To understand the antitumor mechanism, the immunomodulatory activity of C60(OH)x was investigated. The results indicate that C60(OH)x enhances the phagocytosis of peritoneal macrophages and elevates the activity of arginase and acid phosphatase in vivo. The tumor necrosis factor alpha production of C60(OH)x‐treated macrophages also increases in vitro. These results suggest that C60(OH)x can enhance the innate immunity of tumor‐bearing mice, and therefore inhibits growth of the tumor.
Effects of intravenous placebo with glucose expectation on human basal ganglia dopaminergic function
Authors: Haltia Lauri T. , Rinne Juha O. , Helin Semi , Parkkola Riitta , Någren Kjell , Kaasinen Valtteri 
Published: June 2008

AbstractPrevious positron emission tomography (PET) studies have provided evidence that the psychological expectation of certain drugs combined to the placebo administration may lead to subjectively experienced placebo effects, which, in turn, are associated with dopamine (DA) release in the brain. Our recent study indicated that blind intravenous (i.v.) glucose induces DA release in male subjects. In the present study, we examined if the mere expectation of glucose (i.v. placebo) could similarly release DA in the basal ganglia. [11C]raclopride PET was performed for 12 lean [mean body mass index (BMI) = 22 kg/m2] and 12 overweight (mean BMI = 33 kg/m2) healthy subjects (12 men and 12 women). Each subject was imaged twice in a counter‐balanced setting, after blind i.v. placebo and after open i.v. placebo. DA D2 receptor binding potentials (BP) were estimated. The results of the present study show that i.v. placebo administration with glucose expectation induces bilateral BP reduction in the ventral striatum in the male group, suggesting DA release. The stimulus did not induce dopaminergic placebo effect in the overweight or the lean group (males and females combined). Voxel‐based analysis also suggested regionally selective BP increases in the dorsal striatum in the male subjects, whereas women showed no significant changes in BPs. The results support previously reported gender differences in the DA function after a pharmacological challenge (e.g., amphetamine and glucose). Also, they suggest that the DA release in the ventral striatum mediates placebo responses in the context of glucose expectation. Synapse 62:682–688, 2008. © 2008 Wiley‐Liss, Inc.
A classification of biologic lipids based upon their interaction in aqueous systems
Authors: Small Donald M. 
Published: June 2008

AbstractA classification of lipids is presented, based upon their physical properties in bulk aqueous systems and at the air‐water or oil‐water interface. This is supported by binary‐phase diagrams of the various classes of lipids in water.The interactions of the lipids of each class with a lipid of another class is illustrated by a series of different ternary‐phase diagrams of two lipids in water. The various types of association and the molecular relation of one lipid to another are indicated. The interaction of three classes of lipids with water is illustrated in two examples by quaternary‐phase diagrams of the three lipids in water.As an example of the application of these invitro studies, the composition of bile is correlated with a quaternary‐phase diagram cholesterollecithin‐bile salt‐water. The correlation shows that human bile behaves as a biologic four‐component system the physical state of which is entirely predictable from the quaternary‐phase diagram. Although bile is a special case, it is probable that the physical arrangement of the lipids in membranes, cellular organelles, lipoproteins, and adipose tissue can be suggested by studies of the interaction of lipid classes with themselves in water.
Liquid crystals and living systems
Authors: Fergason James L. , Brown Glenn H. 
Published: June 2008

AbstractMost lipids do not pass, on heating, directly from a crystalline structure to an isotropic structure. They are often characterized by a number of intermediate phases, ranging from the plastic crystal, where the center of gravity of the molecule may rotate about one or more axes while the three‐dimensional order of the crystal remains, to nematic liquid crystals, which have birefrigent properties of crystals and yet are characterized by completely random ordering of the molecular centers. The smectic and cholesteric liquid crystalline structures are most commonly encountered in lipids. The structural characteristics of these systems are discussed.Of particular interest in living systems are liquid crystals, which are formed by cholesteric esters and many protein materials, and the two‐dimensional crystals (smectic structure), which are formed by fatty acid derivatives. The mechanisms of energy transfer and the mechanical alignment in these liquid crystalline systems are unique and require different considerations from those found adaptable to liquids or solids. The properties of liquid crystals which might best be associated with living systems will be discussed, including surface properties and diffusivity.
Interaction of soluble proteins with protein monolayers
Authors: Arnold John D. , Pak Charles Y. 
Published: June 2008

AbstractThe direction and strength of intermolecular forces at an air‐water or oil‐water interface is such that many proteins in the interface are distorted in structure. This involves substantial changes in solubility and cross‐sectional area. Many of the changes can be accounted for by rupture of the secondary and tertiary bonds and are often irreversible. The hydrophilic groups of the protein will be concentrated in the aqueous phase and participate in interactions with normal proteins in the supporting solution. It can be shown that certain types of interaction between these hydrophilic groups of a protein monofilm and a soluble protein are dependent on the interfacial pressure, that they are sensitive to a small (one or more amino acid) change in structure of the protein. Evidence is given that they are related to certain antigen‐antibody type reactions between molecules in three‐dimensional systems. Since many proteins in vivo are exposed to oilwater and air‐water interfaces, this laboratory model may have physiologic as well as chemical significance.
Phase equilibria and countercurrent distribution
Authors: Barford R. A. , Bertsch R. J. , Rothbart H. L. 
Published: June 2008

AbstractTernary diagrams for methyl oleate/hexane/acetonitrile and methyl palmitate/hexane/acetonitrile systems were constructed from equilibria data obtained at 20.0 and 30.4C. The diagrams varied significantly with temperature; both systems showed expanded regions of immiscibility at the lower temperature. Both the partition coefficient of the methyl ester and the mutual solubility of hexane and acetonitrile, at each temperature, varied with ester concentration in the system. At high ester concentration, an inversion of the phases was observed. The countercurrent distribution of these compounds, as influenced by these effects, is discussed.
A chromatographic method for the analysis of propylene glycol fatty acid esters in shortenings containing mono‐ and diglycerides
Authors: Sahasrabudhe Madhu R. , Legari J. J. 
Published: June 2008

AbstractA procedure is described for the separation, identification, and quantitative estimation of propylene glycol mono‐ and diesters of lauric, myristic, palmitic, stearic, and oleic acids in shortenings and lard containing mono‐ and diglycerides. Lipid classes are separated on a silicic acid column, and individual esters are estimated by gas chromatography. Analyses of several control mixtures and commercial samples are reported. Recoveries for individual components range from 92 to 105%, and total recoveries range from 96 to 100%.
Dimensional analysis of the detergency process for systems containing multicomponent soils
Authors: Mankowich A. M. 
Published: June 2008

AbstractDimensional analysis of the detergency process has been extended from soil‐surfactant systems which contain a single polar soil to those with binary and ternary component soils which contain a nonpolar ingredient. This was made possible by replacement of the soil dipole moment variable by the proportional square root of orientation polarization (Po) and by establishment of the validity of the empirical volume fraction additivity of the ingredient P0 values of binary polar—polar mixtures by using the classical dilute solution—solute (P2) extrapolation procedure with a chemical oscillometer.
An automated method for determining free alkalinity or acidity in soap
Authors: Hoover W. E. , Ginn M. E. , Jungermann Eric 
Published: June 2008

AbstractAn AutoAnalyzer method has been developed to determine free alkalinity or acidity in soap by use of a mixed cresol red‐phenolphthalein indicator solution and by measurement of the color developed at 550 mµ. An internal standard or reference solution is used consisting of a soap solution which has been adjusted to represent neutrality. The method was applied for 0 to 0.10% free alkalinity, calculated as sodium hydroxide, and for 0 to 0.50% free acidity calculated as oleic acid. Attainable precision of the method (95% confidence limits) in the ranges explored was found to be ±0.0025% for free alkali and ±0.05% for free acidity.
Studies in interesterification. II. Acidolysis of some vegetable oils with lauric acid
Authors: Chakrabarty M. M. , Talapatra K. 
Published: June 2008

AbstractAcidolysis reactions of cottonseed oil, peanut oil, mahua oil (Madhuca latifolia), and palm oil with lauric acid were investigated with special reference to the influence of catalysts and the relative proportions of oil and lauric acid on the extent and type of fatty acids displaced from an oil. Catalysts such as sulfuric acid, zinc oxide, calcium oxide, magnesium oxide, aluminum oxide, and mercuric sulfate were used. The reaction generally was carried out by heating oil and lauric acid at 150C±2 for 3 hr.The reaction products were separated and then analyzed by UV spectrophotometry and GLC. Sulfuric acid was found to be the best catalyst with 1 part of oil and 1.2 parts of the displacing acid (lauric acid) for displacement of high‐molecular‐weight fatty acids from an oil by low‐molecular‐weight fatty acids. The nature of the displacement of fatty acids varied from oil to oil, depending on their compositions. It was further indicated that linoleic acid was displaced preferentially over oleic acid in an amount dependent on its initial content in an oil with a corresponding increase in saturated acids content. A broad similarity in displacement patterns, in general, was noted; the fatty acids above C18 were not displaced as in the case of peanut oil. The results demonstrate the feasibility of introducing lauric acid in the vegetable oils for the production of interesting oils with vastly different physical and chemical properties.
A survey of the conjugated fatty acids of seed oils
Authors: Hopkins C. Y. , Chisholm Mary J. 
Published: June 2008

AbstractFatty acids with conjugated unsaturation occur in many seed oils. Thirty of these acids are reviewed with emphasis on their detection, isolation, and structure determination. Their distribution among plant families is shown, and a botanical source of each acid is given. Some reactions, derivatives, and methods of determining configuration are described. Current theories of their biosynthesis in the seed, involving oxygenated precursors, are summarized.
Solid‐liquid phase relations of some normal long‐chain fatty acids in N,N‐dimethylacetamide and N,N‐dimethylformamide
Authors: Harris James A. , Bailey August V. , Skau Evald L. 
Published: June 2008

AbstractSolubility data are reported for capric, lauric, myristic, palmitic, stearic, and arachidic acids in N,N‐dimethylacetamide (DMA) and N,N‐dimethylformamide (DMF). Complete binary freezing‐point diagrams were constructed for the capric, myristic, and stearic acid systems. A solid, incongruently melting 1:1 molecular compound formed in all except the stearic acid‐DMF system. Calculated solubility data for lauric, palmitic, and arachidic acids in both solvents were in good agreement with experimental determinations on selected compositions.
Removal of cyclopropenoid fatty acids from cottonseed meals by solvent extraction
Authors: Reilich H. G. , O’Neill H. J. , Levi R. S. , Yamauchi T. , Pons W. A. 
Published: June 2008

AbstractDirect solvent‐extraction procedures were explored for their effectiveness in removing the residual levels of cyclopropenoid fatty acids from commercial cottonseed meals. Of the seven solvent systems screened, a simple stepwise extraction with an acetone/hexane/water azeotrope was found suitable for the removal of up to 88% of the original CPA content of the meal.
Reactions of the stearoylated enolic form of acetone, involving hexadecylketene as the reactive intermediate
Authors: Rothman Edward S. 
Published: June 2008

AbstractEnol esters, such as isopropenyl stearate, are useful intermediates capable of forming interesting derivatives of saturated aliphatic fatty acids. Under given conditions, whereas methyl stearate remains unreactive up to 400C, by contrast the isopropenyl stearate ester efficiently liberates hexadecylketene at 170C with the simultaneous expulsion of “isopropenyl alcohol,” i.e., acetone. In the presence of even difficulty acylatable OH or NH compounds the liberated aldoketene combines, usually quantitatively, with these hydrogen‐bearing compounds to form esters or imides. In this manner such resistant materials as barbituric acids, hydantoins, N‐butylstearamide, acetanilide, t‐butyl alcohol, and succinimide may be converted to stearoylated derivatives.In the absence of reactable substrate and with strong dependence on the nature of the reaction medium, liberated hexadecylketene tetramerizes to derivatives ofgamma pyrone, or forms stearone, or stearoylates the enolic rearrangement product, heneicosane‐2,4‐dione. The latter compound, in forming, has increased the 18 carbon chain‐length to 21 continuous carbon atoms. Di‐isopropenyl esters with polyfunctional acetylatable materials, such as bis‐N‐alkylazelaamide or sucrose, give rise to unusual linear polyimides, three‐dimensional network polymers, or oligomers.
A guide for forecasting soybean futures prices
Authors: Malone Patrick J. 
Published: June 2008

AbstractThe role of the spectator is discussed, and emphasis put on his study of fundamental market analysis, such as supply and demand projections; technical market analysis, such as chart trends and composition of open interest; and the basic trading rules for every trader. Both soybean oil and meal are considered. Statistics from the Commodity Exchange Authority are shown to be auxiliary tools.