bluuebunny/crossref_metadata_2025 huggingface dataset:
Response Adaptive Randomization
Authors: Coad D.Stephen
Published: October 2008

When two or more treatments are being compared in a clinical trial, information accrues on the treatments as the trial proceeds. However, there may be evidence suggesting that some treatments are more promising than others, and consequently, there may be interest in applying response adaptive randomization, which uses the current data to assign more patients to the treatments that are performing better thus far in the trial. In this way, patients have a higher probability of being assigned to these treatments. Examples of this type of randomization are given, such as urn models and sequential maximum likelihood estimation rules, and some of their properties are described. The issue of inference after trials that use response adaptive randomization is then discussed. For example, this approach can lead to a loss in power when using standard tests and the problem of estimation can be considerably more complicated than in a trial that uses complete randomization. The use of stopping rules is also addressed, since, in practice, there may be interest in stopping a trial early if there is convincing evidence of a treatment difference or less promising treatments may be dropped from additional consideration. An indication is given of possible future work.
CFR
21 Part 11
Authors: Owings Michael P. , Bleicher Paul A.
Published: October 2008

21CFR11: ELECTRONIC RECORDS; ELECTRONIC SIGNATURES, commonly referred to as “Part 11” was enacted in 1997 to provide criteria under which the FDA will consider electronic records to be equivalent to paper records, and electronic signatures equivalent to traditional handwritten signatures. Part 11 applies to
persons
who, in fulfillment of a requirement in a statute or regulation, have chosen to maintain records or submit designated information electronically to the FDA, and to
records
in electronic form that are created, modified, maintained, archived, retrieved, or transmitted under any records requirements set forth in Agency regulations.
Metadata
Authors: Christiansen David H.
Published: October 2008

Clinical trial metadata, or “data about data” define the characteristics of data and documents related to clinical trials. The most common metadata are attributes of clinical trial datasets submitted in support of a regulatory application for a new medical treatment. Clinical trial reports, regulatory submissions, and statistical analyses can also profit from metadata that clearly describe the content, structure, and use of these documents. Several organizations, including the U.S. Food and Drug Administration, are actively engaged in developing standard metadata for clinical trials. The increasing use of electronic regulatory submissions has heightened the interest in computerized or machine‐readable metadata. Standardized, predictable metadata in a computerized form provide the framework for the development of tools to assist in the creation and review of clinical trial reports and regulatory submissions. Furthermore, standardized metadata will provide the basis for development of review and analysis tools that can be used by both industry and regulators to expedite the timely and accurate evaluation of new medical treatments.
Cronbach's Alpha
Authors: Kraemer Helena Chmura
Published: October 2008

Cronbach's alpha is a measure of internal consistency among m items that are summed or averaged to generate a score characterizing a subject (1), sometimes mistakenly reported as a measure of reliability. Cronbach's alpha is reported as background to the selection of outcome measures in randomized clinical trials.
Subgroup
Authors: Wittes Janet
Published: October 2008

Randomized clinical trials are usually designed to show an effect of treatment in the study population at large. Trials rarely have sufficient statistical power to measure reliably the effect of a treatment within a subgroup of that population. They are even less likely to provide reliable information on whether the effect of a treatment differs from subgroup to subgroup. This article defines various terms related to analysis of subgroups. It distinguishes between subgroups defined on the basis of baseline variables from “improper” subgroups defined on the basis of variables measured after randomization. It also discusses hypotheses defined a priori and those identified after the results have emerged. It emphasizes that random variation arising from small sample sizes can lead to unrealistically large or small observed effects and warns investigators to interpret findings from subgroups with caution.
Regression Models to Incorporate Patient Heterogeneity
Authors: O'Quigley John
Published: October 2008

Although we anticipate heterogeneity among patients included in a dose finding study, given the typically small number of patients available, it is common to group all the patients under a single heading. However, careful modeling can still enable us to make gains when dealing with clearly defined subgroups. Rather than carry out separate independent studies, it is possible via the use of simple regression models to include all patients under one heading while still allowing for the possibility that the groups behave differently. Different schedules of treatment may also lead to different behaviors and, under a working assumption that the groups behave similarly, it is important to have a mechanism that will indicate to us that the accumulating evidence suggests the groups are behaving differently. Regression models can enable us to do this. Certain studies involve more than a single grouping covariable, an example is the two prognostic groups based on heavily and lightly pretreated patients, together with a variable that labels the scheduling. For three different schedules and two prognostic groups, we have a total of six subgroups. Separate analyses are not feasible, and a regression model can be of great use in such situations.
UGDPTrial
Authors: Meinert Curtis
Published: October 2008

The UGDP (University Group Diabetes Program) was a multicenter, randomized, placebo‐controlled trials aimed at assessing the efficacy of antidiabetic treatments in delaying or preventing the long‐term complications of adult‐onset diabetes (type‐2 diabetes). The trial was in the carly vanguard of trials aimed at assessing efficacy of approved treatments for chronic conditions—phase IV trials in the vernacular of trials. The trial involved two oral agents, tolbutamide and phenformin, and matching placebos and two insulin‐assigned treatment groups (insulin dosage as determined by body surface and insulin dosage as needed to “normalized” blood glucose levels). The trial generated a firestorm of controversy in 1970 with presentation and publication of results suggesting that a widely used oral agent—tolbutamide (Orinase, Upjohn, Kalamazoo now part of Pfizer)—was of no value in reducing the risk of morbiarty or in prolonging life. The FDA used its results to revise the label for the drug to include a special warning concerning the possibility cardiovascular risks associated with the drug, but only after a prolonged battle that raged on for more than a decade—a battle that ultimately ended up in front of the U.S. Supreme Court.
Conditional Power in Clinical Trial Monitoring
Authors: Tan Ming T.
Published: October 2008

For ethical, economical, and scientific reasons, clinical trials may be terminated early for treatment efficacy or the lack thereof. In addition to group sequential tests and type I error‐spending functions, another approach is to ask more directly whether the accumulated evidence is sufficiently convincing for efficacy. Or, if evidence is lacking, one would ask whether the trial should continue to the planned end and whether the conventional fixed sample (nonsequential) test should be employed. Conditional power is one way to quantify this evidence. It is the power of the conventional nonsequential test conditional on interim data. This article introduces the versatile conditional power and related stochastic curtailment approaches in the monitoring of clinical trials.
Incompetent Subjects and Proxy Consent
Authors: Glantz Leonard H.
Published: October 2008

Research with incompetent subjects presents the most serious ethical challenges than any other category of research. Special limitations are set on the types of research that can be conducted with this population. Both researchers and those who provide surrogate consent have obligations to protect the rights and welfare of this population that exceed those duties owed to competent subjects.
Phase I Trials
Authors: Chevret Sylvie
Published: October 2008

Phase I trials, which are also called first‐into‐human studies, try to determine dosing, to document how a drug is metabolized and excreted, and to identify acute side effects. Usually, a small number of healthy volunteers (between 20 and 40) is used. They evaluate how well a new drug is tolerated, with the principal observations of interest being the pharmacokinetic and pharmacodynamic endpoints. Designs are often fixed, in which several dose levels and a placebo are randomly given, possibly in different periods, although some ascension is often conducted over the periods. At the other end of the severity spectrum, oncology Phase I trials are conducted in patients to determine the highest dosage that can be given safely, which is usually called the maximum tolerated dose (MTD). The designs are sequential and adaptive in some sense, because each patient is administered a dose level on the light of previous doses, and outcomes are observed in the trial. Two main adaptive designs are used, with dose allocation either algorithm‐ or model‐guided. They differ in terms of underlying interpretation of the MTD. The aim of this article is to summarize the most usual Phase I designs and analyses conducted in healthy volunteers and in oncology patients, separately. Differences between these approaches are stressed out, with some practical recommendations.
Therapeutic Dose Range
Authors: Sylvie Chevret
Published: October 2008

After preclinical assessments, the therapeutic dose range emphasizes the importance of the margin of safety that exists between the dose required for the desired effects of the drug and the dose that produces unwanted—potentially dangerous—side effects in determining the usefulness of a drug. The narrower the margin, the more likely it is that the drug will produce unwanted effects. This therapeutic index relies of the assessment of dose–response relationship. Traditional drug development consists of a sequence of independent trials organized in different phases. However, when establishing dose–response relationships and potential therapeutic dose range, over‐reliance on premarketing clinical trials has been pointed out. Assessment of dose–response relationships should occupy a prominent role in drug development with clinical studies designed to assess dose response as an inherent part of establishing the safety and effectiveness of the drug. This research relies on phase I studies in healthy volunteers with collected data on safety, tolerability, and effectiveness, as well as pharmacokinetics and pharmacodynamics. By contrast, drug development in life‐threatening diseases specifically uses the maximum tolerated dose as the only dose of interest. In all cases, note that the therapeutic dose range is based on small sample studies; thus, it makes it difficult or even impossible to individualize treatment based on patients' specific characteristics such as age, size, state of health, or use of concomitant medications. This discrepancy deserves additional attention.
Intrarater Reliability
Authors: Gwet Kilem L.
Published: October 2008

Intrarater reliability refers to the ability of a rater or a measurement system to reproduce quantitative or qualitative outcomes under the same experimental conditions. In this article, we review two statistical measures often used in the literature for quantifying intrarater reliability. The first measure is the intraclass correlation coefficient (ICC), which is the preferred measure for continuous data. The second measure is the kappa coefficient and its many kappa‐like variants recommended for nominal data. Also included in this article are guidelines for optimizing the number of subjects and number of replicates per subject when designing an intrarater reliability study for quantitative measurements. We also explore important extensions of the kappa coefficient to ordinal and interval data, which may also be used to analyze multivariate ratings obtained by rating subjects on multiple characteristics. For the intraclass correlation coefficient and kappa‐like statistics, we discuss a framework for statistical inference within which to evaluate the precision of estimations.
The FDA and Regulatory Issues
Authors: Rzeszotarski W. Janusz
Published: October 2008

A brief outline of information that is available on the Web pertinent to the FDA and regulatory issues. The process of new drug approval and its continuous modification reflects both the progress of science and the globalization of the world's economy. The reader is encouraged to follow the changes by constant monitoring of the FDA and the industry sites dedicated to these issues. The history of drug regulation in the United States, the evolving structure of the FDA, the steps to be taken in the process of obtaining the approval to market the new molecular entity, and the post‐approval requirements are briefly described.
Censored Data
Authors: Andersen Per Kragh
Published: October 2008

The concepts of independent right censoring and noninformative right censoring in survival analysis are defined. Dependent censoring is a kind of selection bias and adds to biased inference for the survival time distribution. Informative censoring typically leads to inefficient inference. Examples are presented and relations between right censoring and competing risks are discussed. Other kinds of censoring, including interval censoring are touched upon.
Kappa
Authors: Cook Richard J.
Published: October 2008

The kappa statistic is a widely used measure for quantifying agreement between two methods of classification into nominal categories. Part of the appeal of the kappa statistic is that it is a “chance‐corrected” measure, which reflects agreement beyond the level expected by chance based on the marginal frequencies. Generalizations to weighted kappa statistics are appealing for the analysis of ordinal data. Generalizations of the original kappa statistic facilitate agreement analyses between three or more raters.
Nonparametric Methods
Authors: Wolfe Douglas A.
Published: October 2008

The motivation behind distribution‐free hypothesis tests and confidence intervals based on signs and ranks is discussed and standard text references are provided. Distribution‐free test and confidence interval procedures for the one‐sample, two‐sample, one‐way analysis of variance, two‐way analysis of variance, and independence settings are presented. Point estimation techniques, including Hodges–Lehmann estimators and contrast estimation, and multiple comparisons procedures are described. Basic references for censored data approaches and bootstrapping are provided.
P

Value
Authors: Goodman Steven N.
Published: October 2008

The
P
value is the probability, under a given simple hypothesis, of the observed or a more extreme value of a test statistic. Problems discussed include that of the choice of test statistic, the relevance of alternative hypotheses, ambiguity about the sample space, and the interpretation generally. The distinction between one‐sided and two‐sided tests is a source of confusion. Bayesian considerations are discussed.
Survival Analysis, Overview
Authors: Andersen Per Kragh , Keiding Niels
Published: October 2008

Survival analysis is the generic name for analysis of time‐to‐event data. The distinguishing feature of such data is the presence of right‐censored observations. Thus, for some subjects, instead of observing the real time to the event, only a lower limit for this time, the right‐censoring time, is known. This kind of incomplete data calls for special statistical techniques for the analysis. This article reviews such methods with cross‐references to other articles dealing with special techniques.
Benefit/Risk Assessment in Prevention Trials
Authors: Costantino Joseph P.
Published: October 2008

Benefit/risk assessment (B/RA) is a mathematical procedure to estimate the probability of detrimental outcomes, beneficial outcomes and the net‐effect anticipated from exposure to a given agent or procedure. B/RAs of health‐related outcomes are used for public health planning, decision‐making regarding health care financing, and therapeutic decision‐making in clinical practice. Information obtained from B/RAs based on findings from controlled clinical trials, particularly those with double‐masking of treatment, are most informative for health care planning and decision making because such information is less likely to be bias than is information obtained from observational studies. Thus, B/RAs in prevention trials are an excellent source of information to use as the basis for health care planning and decision‐making. Applications of R/BA in prevention trials are performed as supplements for planning, monitoring and analyzing the trial. These applications can be categorized into three types of assessments. This article provides a description of the three types of assessment performed in prevention trials, defines the statistical algorithms used for each type of assessment and discusses several key methodological and practical issues involve with the application of B/RA to health‐related outcomes.
Compliance and Survival Analysis
Authors: Goetghebeur Els
Published: October 2008

Partial compliance with assigned treatment can act as both cause and effect of survival experiences in randomized clinical trials. Structural failure time models have been developed for causal inference on the effect of resulting exposure patterns on survival time. In this setting, we review randomization based estimation methods that protect the standard α level. We also point to alternative methods relying on the assumption of no unmeasured time‐dependent confounders.
Sequential Analysis
Authors: Lai T. L.
Published: October 2008

This article gives an overview of sequential analysis and its applications to data and safety monitoring of clinical trials, determination of median effective dose and maximum tolerated dose, fixed‐width confidence intervals, and adaptive design of biomedical studies.
Pharmacoepidemiology, Overview
Authors: Suissa S.
Published: October 2008

Pharmacoepidemiology is the study of patterns of medication use in the populations and their effects on diseases. Particular interest is focused on unexpected risks, especially events such as rare side effects. These can typically not be adequately assessed in the context of randomized clinical trials. This entry describes the use of Pharmacoepidemiology through the case‐crossover design, dealing with confounding in observational studies, the specification of appropriate risk functions over time, the probabilistic assessment of causality, and study methods based on the use of prescription data.
Genetic origins and clinical phenotype of familial and acquired erythrocytosis and thrombocytosis
Authors: Percy Melanie J. , Rumi Elisa
Published: October 2008

Familial and acquired erythrocytosis and thrombocytosis are characterized by myeloid lineage hyperproliferation, which is either single or multi‐lineage in origin. The single lineage disorders exhibit Mendelian inheritance with polyclonal hematopoiesis and often arise from a single genetic defect. In contrast, the multi‐lineage disorders exhibit complex patterns of inheritance with multi‐genetic origins and clonal hematopoiesis. They have the potential to acquire JAK2 somatic mutations, but this is not the primary event. Identification of the disease‐causing genes will enable better classification of familial and acquired erythrocytosis and thrombocytosis. Furthermore, it will provide an insight into the mechanisms regulating myeloid cell proliferation. Am. J. Hematol., 2009. © 2008 Wiley‐Liss, Inc.
Tetra‐amelia and lung hypo/aplasia syndrome: New case report and review
Authors: Sousa Sérgio B. , Pina Raquel , Ramos Lina , Pereira Naigel , Krahn Martin , Borozdin Wiktor , Kohlhase Jürgen , Amorim Marta , Gonnet Katia , Lévy Nicolas , Carreira Isabel M. , Couceiro Ana Bela , Saraiva Jorge M.
Published: October 2008

Tetra‐amelia is a rare malformation that may be associated with other anomalies and is usually inherited in an autosomal recessive pattern. We describe a fetus, born to a nonconsanguineous couple, with tetra‐amelia, bilateral cleft lip and palate and bilateral lung agenesis, without other anomalies. Karyotype was normal (46,XX) and premature centromere separation was excluded. No mutation was identified upon molecular analysis of WNT3, HS6ST1, and HS6ST3. We reviewed the literature and the differential diagnosis to clarify the clinical delineation of conditions associated with tetra‐amelia. The present report describes the sixth family with this pattern of malformations and reinforces the evidence that the “tetra‐amelia and lung hypo/aplasia syndrome” is a distinct autosomal recessive condition, with no identified gene thus far. © 2008 Wiley‐Liss, Inc.
Testing the function of reconciliation and third‐party affiliation for aggressors in hamadryas baboons (Papio hamadryas hamadryas)
Authors: Romero Teresa , Colmenares Fernando , Aureli Filippo
Published: October 2008

In social groups, agonistic conflicts can have different negative consequences. Several post‐conflict interactions have been suggested as post‐conflict management behaviors to mitigate those negative effects. In this study, we investigated the function of two post‐conflict behaviors—reconciliation and aggressor‐initiated third‐party affiliation—on the aggressor's levels of post‐conflict anxiety and aggression in a large colony of hamadryas baboons. We also examined variation in the aggressor's levels of post‐conflict anxiety as a function of relationship quality between the opponents as predicted by the Integrated Hypothesis. We found that after conflicts hamadryas baboon aggressors showed increased rates of anxiety‐related behaviors and that they were also more likely to be involved in renewed aggressive interactions. Although both reconciliation and aggressor‐initiated third‐party affiliation reduced the probability of receiving post‐conflict aggression, only reconciliation reduced the rates of anxiety‐related behaviors, suggesting that the aggressors' post‐conflict anxiety might be owing mainly to the damage that the conflict causes to their relationship with the victim. Furthermore, aggressor's rates of post‐conflict anxiety were higher after conflicts with individuals with whom they had a high‐quality relationship, supporting the idea that levels of post‐conflict anxiety mediate the occurrence of reconciliation depending on the quality of the relationship with former opponent as predicted by the Integrated Hypothesis. Am. J. Primatol. 71:60–69, 2009. © 2008 Wiley‐Liss, Inc.
Opsin gene polymorphism predicts trichromacy in a cathemeral lemur
Authors: Veilleux Carrie C. , Bolnick Deborah A.
Published: October 2008

Recent research has identified polymorphic trichromacy in three diurnal strepsirrhines: Coquerel's sifaka (Propithecus coquereli), black and white ruffed lemurs (Varecia variegata), and red ruffed lemurs (V. rubra). Current hypotheses suggest that the transitions to diurnality experienced by Propithecus and Varecia were necessary precursors to their independent acquisitions of trichromacy. Accordingly, cathemeral lemurs are thought to lack the M/L opsin gene polymorphism necessary for trichromacy. In this study, the M/L opsin gene was sequenced in ten cathemeral blue‐eyed black lemurs (Eulemur macaco flavifrons). This analysis identified a polymorphism identical to that of other trichromatic strepsirrhines at the critical amino acid position 285 in exon 5 of the M/L opsin gene. Thus, polymorphic trichromacy is likely present in at least one cathemeral Eulemur species, suggesting that strict diurnality is not necessary for trichromacy. The presence of trichromacy in E. m. flavifrons suggests that a re‐evaluation of current hypotheses regarding the evolution of strepsirrhine trichromacy may be necessary. Although the M/L opsin polymorphism may have been independently acquired three times in the lemurid–indriid clade, the distribution of opsin alleles in lemurids and indriids may also be consistent with a common origin of trichromacy in the last common ancestor of either the lemurids or the lemurid–indriid clade. Am. J. Primatol. 71:86–90, 2009. © 2008 Wiley‐Liss, Inc.
Effects of prior aging at 288°C in air and in argon environments on creep response of PMR‐15 neat resin
Authors: Ruggles‐Wrenn M. B. , Broeckert J. L.
Published: October 2008

The creep behavior of PMR‐15 neat resin, a polyimide thermoset polymer, aged in air and in argon environments at 288°C for up to 1000 h was evaluated. Creep tests were performed at 288°C at creep stress levels of 10 and 20 MPa. Creep periods of at least 25‐h in duration were followed by 50‐h periods of recovery at zero stress. Prior isothermal aging increased the elastic modulus and significantly decreased the polymer's capacity to accumulate creep strain. The aging environment had little influence on creep and recovery behaviors. However, aging in air dramatically degraded the tensile strength of the material. Dynamic mechanical analysis revealed an increase in the glass transition temperature from ∼330°C to ∼336°C after 1000 h in argon or in air at 288°C. The rise in the glass transition temperature with aging time is attributed to an increase in the crosslink density of the PMR‐15 polyimide. Increase in the crosslink density due to aging in both air and argon environments is likely behind the changes in the elastic modulus and the decreased capacity for inelastic straining. A visibly damaged surface layer of ∼0.16 mm thickness was observed in specimens aged in air for 1000 h. Results indicate that the unoxidized core material governs the overall mechanical response, whereas the oxidized surface layer causes a decrease in tensile strength by acting as a crack initiation site and promoting early failures. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Fabrication and morphology control of poly(methyl methacrylate) hollow structures via coaxial electrospinning
Authors: Chan Kok Ho Kent , Kotaki Masaya
Published: October 2008

A modified electrospinning method known as coaxial electrospinning was used to fabricate poly(methyl methacrylate) (PMMA) hollow structures. In this study to understand morphology control, the effect of processing parameters such as concentration of polymer sheath solution, size of core/sheath capillaries, feed rate, and applied voltage had been evaluated. Morphological observations via scanning electron microscope (SEM) revealed that via the control of polymer concentration within the sheath solution, morphologies such as hollow particles and fibers could be obtained. With the use of fine core/sheath capillaries, micron hollow fibers with walls of less than 20 nm were obtained. This study has demonstrated how the investigated processing parameters have a direct influence on the structures and how these parameters have supported the notion that effective encapsulation process is the key to the dual layer bicomponent structures. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Mechanism of bubble formation in the drying of polymer films
Authors: Pourdarvish Reza , Danner Ronald P. , Duda J. Larry
Published: October 2008

A common problem in making thin polymer films by solution processing is the undesirable formation of bubbles during the drying process. These bubbles appear well below the boiling point of the solvent. Experience indicates, however, that the degassing of the polymer solutions reduces bubble formation, indicating a relationship with the presence of air. This work is based on a hypothesis that if the solubility of air in the polymer solution increases with solvent concentration, then the solution can become supersaturated with air as the concentration of the solvent is reduced during the drying process. To test this hypothesis the system poly(vinyl acetate)‐toluene‐nitrogen was chosen. Previously published data on the solubility and diffusion of nitrogen in the polymer‐solvent system were used. Different diffusion models based on the friction coefficients and free‐volume model were then used to correlate the diffusivity data so that the diffusion behavior of the ternary system can be predicted over a broad range of conditions. Finally, the thermodynamic and diffusivity correlations were incorporated into a multicomponent drying model which included main and cross‐diffusion terms to predict saturation behavior in the polymer solution during the drying process. The model without the cross‐diffusion terms represents the ideal system in which the diffusion of one component does not affect the diffusion of others. The drying model did not predict supersaturation of nitrogen when cross‐diffusion terms were neglected. Supersaturation of nitrogen was predicted, however, when the cross‐diffusion terms are included. Therefore, the cross‐diffusion terms in the mass transfer model are essential for the development of nitrogen supersaturation. Also different diffusion models based on the friction coefficients led to qualitatively similar predictions for the supersaturation of nitrogen. The simulation's results supported our experimental observations regarding bubble formation. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Evaluation and simulation of the peel behavior of polyethylene/polybutene‐1 peel systems
Authors: Nase Michael , Langer Beate , Baumann Hans Joachim , Grellmann Wolfgang , Geißler Gordon , Kaliske Michael
Published: October 2008

The peel characteristics of sealed low‐density polyethylene/isotactic polybutene‐1 (PE‐LD/iPB‐1) films, with different contents of iPB‐1 up to 20 m.‐% (mass percentage), were evaluated and simulated in dependence on the iPB‐1 content, and in dependence on the peel rate. Sealing involves close contact and localized melting of two films for a few seconds. The required force, to separate the local adhered films, is the peel force, which is influenced, among others, by the content of iPB‐1. The peel force decreases exponentially with increasing iPB‐1 content. Transmission electron microscopy studies reveal a favorable dispersion of the iPB‐1 particles within the seal area, for iPB‐1 concentrations ≥6 m.‐%. Here, the iPB‐1 particles form continuous belt‐like structures, which lead to a stable and reproducible peel process. The investigation of the peel rate‐dependency on the peel characteristics is of important interest for practical applications. The peel force increases with increasing peel rate by an exponential law. A numerical simulation of the present material system proves to be useful to comprehend the peel process, and to understand the peel behavior in further detail. Peel tests of different peel samples were simulated, using a two‐dimensional finite element model, including cohesive zone elements. The established finite element model of the peel process was used to simulate the influence of the modulus of elasticity on the peel behavior. The peel force is independent of the modulus of elasticity, however, the peel initiation value increases with increasing modulus of elasticity. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Effect of bis(3‐triethoxysilylpropyl) tetrasulfide on the crosslink structure, interfacial adhesion, and mechanical properties of natural rubber/cotton fiber composites
Authors: Zeng Zheng , Ren Wentan , Xu Chi , Lu Weiqiang , Zhang Yong , Zhang Yinxi
Published: October 2008

Bis(3‐triethoxysilylpropyl) tetrasulfide (TESPT) was used to improve the interfacial adhesion between cotton fiber and natural rubber (NR). The crosslink density, interfacial adhesion, mechanical properties, dynamic mechanical properties, and morphology of NR/cotton fiber composites were investigated. The composites with TESPT had higher crosslink density, better mechanical properties, higher initial modulus, and higher yield strength than the composites without TESPT because of the difference in interfacial adhesion. The results of an interfacial adhesion evaluation, the high storage modulus and low damping values of the composites with TESPT, and the coarse surfaces of the pullout fibers implied the enhancement of interfacial adhesion. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
A novel method for the determination of cell infiltration into nanofiber scaffolds using image analysis for tissue engineering applications
Authors: Semnani Dariush , Ghasemi‐Mobarakeh Laleh , Morshed Mohammad , Nasr‐Esfahani Mohammad‐Hossein
Published: October 2008

One of the major themes in tissue engineering is scaffold fabrication. The porosity and pore size of scaffolds play a critical role in tissue engineering. Different methods are used to measure the porosity and pore size of scaffolds, although none can predict the cell infiltration for various cell sizes, shapes, and configurations. The aim of this study was to predict the cell infiltration of various cells with different sizes, shapes, and configurations through the use of image analysis. In this study, cell models were used to predict cell infiltration into nanofiber scaffolds. The results of this study showed that with increases in the cell size and the number of layers of nanofibers, the number of cells that could infiltrate the scaffolds decreased. In addition, the cell configuration had some effect on cell infiltration into the nanofiber scaffolds. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Reactivity ratios and monomer partitioning in the microemulsion copolymerization of vinyl acetate and butyl acrylate
Authors: Ovando‐Medina Víctor M. , Martínez‐Gutiérrez Hugo , Mendizábal Eduardo , Corona Miguel A. , Peralta René D.
Published: October 2008

The true monomer reactivity ratios for the vinyl acetate/butyl acrylate system were determined with experimental data from the cumulative copolymer composition at low, intermediate, and high conversions and with the monomer partitioning among the aqueous, microemulsion droplet, and polymer particle phases taken into account. A mixture of sodium dodecyl sulfate and poly(ethylene oxide) (23) dodecyl ether (Brij‐35; 3 : 1 w/w) was used as a stabilizer. Potassium persulfate was used as an initiator. The true values of the monomer reactivity ratios were 0.028 ± 3.2 × 10−3 for vinyl acetate and 6.219 ± 3.1 × 10−1 for butyl acrylate, and these were in agreement with those reported in the literature for bulk copolymerizations but differed from values reported for other compartmentalized copolymerizations. Thus, these results indicate that the monomer partitioning and cumulative copolymer composition throughout the reaction have to be duly accounted for in the determination of monomer reactivity ratios in heterogeneous polymerizations. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Water‐soluble poly(ethylene glycol) prodrug of pemetrexed: Synthesis, characterization, and preliminary cytotoxicity
Authors: Min Tao , Ye Hai , Zhang Peng , Liu Jun , Zhang Can , Shen Wenbin , Wang Wan , Shen Longsheng
Published: October 2008

Pemetrexed is a novel antifolate of antimetabolite with multiple enzyme targets involved in both pyrimidine and purine synthesis. It has entered the clinical usage due to favorable profiles especially in the cancer treatment of mesothelioma and non–small‐cell lung carcinoma. But it presents numerous challenges associated with poor water solubility and unstability in its original form of glutamic acid. The aim of this study is to solubilize pemetrexed by designing and synthesizing its aqueous‐soluble prodrug using high aqueous‐soluble polymeric carrier poly(ethylene glycol) (PEG). A new type of soluble pemetrexed prodrug was synthesized with dihydroxyl PEG and a single amino acid linkage, and was extensively characterized using 1H‐NMR, 13C‐NMR, Fourier‐transform infrared, and matrix‐assisted laser desorption time of flight mass spectrometry. In addition, the prodrugs were evaluated for the drug loading capability, the aqueous solubility, and the preliminary in vitro cytotoxicity. The results indicate that the new PEGylated pemetrexed conjugates possess enhanced water solubility and stability, and provide another feasible choice of the pharmaceutical form of pemetrexed in the clinical application. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Surface treatment of phosphate glass fibers using 2‐hydroxyethyl methacrylate: Fabrication of poly(caprolactone)‐based composites
Authors: Khan Ruhul A. , Parsons A. J. , Jones I. A. , Walker G. S. , Rudd C. D.
Published: October 2008

2‐Hydroxyethyl methacrylate (HEMA) solution (1–10 wt %) was prepared in methanol and phosphate glass fibers were immersed in that solution for 5 min before being cured (irradiation time: 30 min) under UV radiation. Maximum polymer loading (HEMA content) was found for the 5 wt % HEMA solution. Degradation tests of the fibers in aqueous medium at 37°C suggested that the degradation of the HEMA‐treated fibers was lower than that of the untreated fibers. X‐ray photoelectron spectroscopy revealed that HEMA was present on the surface of the fibers. Using 5 wt % HEMA‐treated fibers, poly(caprolactone) matrix unidirectional composites were fabricated by in situ polymerization and compression molding. For in situ polymerization, it was found that 5 wt % HEMA‐treated fiber‐based composites had higher bending strength (13.8% greater) and modulus (14.0% greater) than those of the control composites. For compression molded composites, the bending strength and modulus values for the HEMA‐treated samples were found to be 27.0 and 31.5% higher, respectively, than the control samples. The tensile strength, tensile modulus, and impact strength of the HEMA composites found significant improvement than that of the untreated composites. The composites were investigated by scanning electron microscopy after 6 weeks of degradation in water at 37°C. It was found that HEMA‐treated fibers inside the composite retained much of their original integrity while the control samples degraded significantly. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Experimental determination of concentration‐dependent carbon dioxide diffusivity in LDPE
Authors: Tendulkar J. , Upreti S. R. , Lohi A.
Published: October 2008

In this work, we experimentally determine the concentration‐dependent diffusivity of carbon dioxide in low‐density poly(ethylene) (LDPE). For this purpose, experiments are carried out to obtain pressure‐decay data for isothermal diffusion of the gas in the polymer. Based on a detailed mass transfer model, variational calculus is used to establish the conditions necessary to yield the concentration‐dependent diffusivity that enables the model‐predicted mass of absorbed gas in polymer to match with the experimental counterpart. A computational algorithm is implemented to solve the model and the conditions and obtain the diffusivities. Determined at 120 and 130°C for four different pressures in the range 0.352 to 1.232 MPa, the diffusivities are strong unimodal functions of gas concentration in polymer and of the order 10−9 m2 s−1. Mathematical correlations are developed to calculate the diffusivity at a given temperature, pressure, and gas concentration. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Synthesis and pH‐induced phase transition behavior of PAA/PVA nanogels in aqueous media
Authors: Yao Ri‐Sheng , You Qi‐Dong , Liu Peng‐Ju , Xu Yu‐Fu
Published: October 2008

Polyacrylic acid (PAA) and polyvinyl alcohol (PVA) are well‐known FDA‐approved biocompatible polymers. A novel method for preparing PAA/PVA complex nanoneedles in PVA aqueous solution is presented in this article. The PAA/PVA complex nanogels are obtained via polymerization of acrylic acid monomer after PVA nanoparticles formed in water/acetone cosolvent. The results of TEM images showed that the PVA chains were aggregated to form gel particles with some erose nanoparticles. As AA monomers polymerized around PVA nanoparticles, PAA/PVA complex nanogels formed. The PAA/PVA nanogels had an average diameter of 300–100 nm with AA concentration of 0.5–2 g/100 mL. As acetone concentration varied, TEM images demonstrated that the morphologies of resulting nanogels are different. Without acetone in PVA aqueous solution, however, PAA/PVA complexes aggregated to form earthnut‐like particles. These results show that the shape and size of PVA/PAA nanogels can be tailored as a template or core for the formation of PAA/PVA nanogels. These PAA/PVA nanogels exhibited pH‐induced phase transition due to protonation of PAA chains. The novel PVA/PAA nanogels promise to be developed into pH‐controlled drug delivery system. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Batch emulsion polymerization of vinyl chloride: Application of experimental design to investigate the effects of operating variables on particle size and particle size distribution
Authors: Pourmehr Mahdi , Navarchian Amir H.
Published: October 2008

In this article, the influences of operating variables on the particle size (PS) and particle size distribution (PSD) of emulsion poly(vinyl chloride) in batch reactor were investigated using Taguchi experimental design approach. The variables were temperature (T), water to monomer weight ratio (R), concentrations of initiator ([I]) and emulsifier ([E]), and agitation speed (S). Scanning electron microscope was used together with image analysis software to determine the PS and PSD. Statistical analysis of results revealed that the PS of emulsion poly(vinyl chloride) strongly depends on emulsifier and initiator concentrations, respectively, whereas the other factors have no significant effects in the range of levels investigated in this study. Except initiator concentration, all factors have important influence on the PSD (significance sequence: S > R > T > [E]). It is implied from the greater influence of agitation speed relative to temperature on PSD that the shear coagulation predominates the Brownian coagulation in this system. The relative optimum condition for a typical paste application was also determined using overall evaluation criteria. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Thermal degradation behavior of PMMA synthesized by emulsifier‐free emulsion polymerization with a Cu2+/HSO3− redox system
Authors: Chiu Tso‐Pei , Don Trong‐Ming
Published: October 2008

In this study, poly(methyl methacrylate) (PMMA) latex was synthesized in an emulsifier‐free emulsion polymerization at 60°C using a Cu2+/HSO redox initiator system with different concentrations of Cu2+. The experimental results showed that the monomer conversion reached above 90% for all systems. Zeta potential was all negative due to the bonded bisulfite ion and the magnitude was greater than 30 mV, providing the stability of PMMA emulsion. The morphology of the latex observed by scanning electron microscope revealed a uniform particle size, and the average particle size increased from 181.9 to 234.2 nm as the Cu2+ ion concentration increased from 2.0 to 6.0 mM in 1M of MMA solution. Thermal degradation behavior of synthesized PMMA was studied by thermogravimetric analysis, in which a two‐stage degradation behavior was observed. These two stages were found to be caused by the degradation of unsaturated end group (PMMACRCH2) and saturated end group (PMMAH), respectively. In addition, the higher the concentration of Cu2+ ion, the greater the proportion of PMMACRCH2 in the final product, and in turn rendering more weight loss in the first‐stage degradation. The copper ion not only played a role in the redox initiation, but also acted as a chain transfer agent to terminate growing polymer chains, thus producing PMMACRCH2. The apparent activation energies of the first stage (Ea1) and second stage (Ea2) were calculated by Ozawa's and Boswell's method. The results showed that Ea1, representing the degradation of PMMA‐CRCH2, was lower than Ea2 for the degradation of PMMA‐H. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Determination of the phase diagram of HBA‐HNA liquid crystalline polymer/polycarbonate blends
Authors: Lee Kam‐Wa D. , Chan Philip K. , Kamal Musa R.
Published: October 2008

The phase diagram of blends of liquid crystalline polymer (LCP) and polycarbonate (PC) was constructed. The effect of temperature on morphological development in melt‐blended samples was examined with a polarized light microscope, in conjunction with a heating stage. Phase separation in the blend was observed as the temperature was increased. For a particular LCP/PC blend composition, two‐phase separation temperatures (Tsp1 and Tsp2) were determined. Consequently, the corresponding phase diagram relating to phase separation was constructed. It was divided into three regions. No phase separation occurred when the blend was below Tsp1. However, a slight phase separation was detected when the temperature was between Tsp1 and Tsp2. Moreover, pronounced phase separation was observed when the blend was at a temperature above Tsp2. The phase‐separated structure varied according to the initial composition of the blends. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Optimization of operating conditions in a single‐zone drier for two‐layer polymer coatings
Authors: Khandelwal A. , Singhania M. , Vinjamur M.
Published: October 2008

In industrial dryers, hot air is blown over wet coatings either from top or from both top and bottom sides to remove the solvent. Drying of multilayer coatings is a complicated process that involves simultaneous heat and mass transfer, transport, and thermodynamic behavior of polymer solutions. Airflow and its temperature are important operating conditions in a dryer. We report optimization of the operating conditions to minimize residual solvent without inducing blisters for two‐layer coatings using mathematical modeling. Our results reveal that optimal air flow on the bottom side of the coating is always greater than or equal to that on its top side—an agreement with the common notion of “backside drying.” Furthermore, the effect of coating thickness, residence time, individual layer thickness, initial solvent concentration, and reversal of the two layers on the optimal conditions is discussed. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Miscibility of polymethylmethacrylate and polyethyleneglycol blends in tetrahydrofuran
Authors: Selvakumar M. , Bhat D. Krishna , Renganathan N. G.
Published: October 2008

The miscibility of polymethylmethacrylate (PMMA) and polyethyleneglycol (PEG) blends in tetrahydrofuran (THF) has been investigated by viscosity, density, refractive index, and ultrasonic velocity studies. Various interaction parameters such as polymer–solvent and blend–solvent interaction parameters and heat of mixing have been calculated using the viscosity, density, and ultrasonic velocity data. The results indicated the existence of positive interactions in the blend polymer solutions and that they are miscible in THF in the entire composition range. The study also revealed that variation in the temperature does not affect the miscibility of PMMA and PEG blends in THF significantly. The presence of hydrogen bonding in the blends in the solid state has also been indicated by FTIR studies. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009