bluuebunny/crossref_metadata_2025_split huggingface dataset:
PhaseIIITrials
Authors: Mallinckrodt Craig , Whitmyer Virgil 
Published: December 2007

AbstractThe objective of phase III clinical trials is to confirm the preliminary but inconclusive evidence obtained from phase II studies that a drug is safe and effective for the intended indication in the relevant patient population. Phase III studies provide the primary basis upon which drugs are approved for use by the various regulatory agencies. Because no universally best approach to phase III research exists, it is important to tailor features of the study to the specific situation at hand. This article focuses on the key aspects of the design, conduct, and analysis of phase III trials and the trade‐offs between them that are necessary to consider when designing a trial intended to yield confirmatory evidence of a drug's effect. Nevertheless, even the best designed trials will have limitations. Any one trial may address its primary hypotheses with little or no ambiguity while other important questions remain unresolved. Therefore, information from the current trial, coupled with knowledge from earlier trials, is used to continually reevaluate what is known. With this knowledge one must reconsider what important questions remain unresolved, and continue to plan and conduct appropriate studies to address the unresolved questions.
Simple Randomization
Authors: Perevozskaya Inna T. 
Published: December 2007

Abstract
An overview of general concept of randomization is given, and its importance as a crucial part of the study design to avoid selection bias is stressed. Simple randomization is the first and most intuitive of the randomization methods. Other, more sophisticated, methods of randomization are highlighted. We discuss properties of the simple randomization and its relationship to other randomization methods. Concept and properties of stratified randomization are discussed as well.
Enrichment Design
Authors: Fedorov Valerii V. , Liu Tao 
Published: December 2007

AbstractEnrichment designs usually consist of two or three stages, where the first stage serves as a screening process for selecting a certain subpopulation, and the succeeding stages serve to distinguish the treatment effect from the placebo effect, within the selected (enriched) subpopulation. The efficiency of its efficacy (response) detection comes at the expense of the ability to make inferences for the general population; that is, the results are valid only for the selected subpopulation. At the same time, if a valid partitioning of the population is proven, then it might be viewed as evidence of “latent” classifiers, which can be targeted for a search. Statistical analysis commonly makes explicit use of the outcomes from only the selected subpopulation (final stage). Some simple models can take advantage of the outcomes from all stages. Most published studies using these designs have been conducted in the field of clinical oncology, but enrichment designs have become increasingly popular in various therapeutic areas.
Therapeutic Equivalence
Authors: Wiens Brian L. 
Published: December 2007

Abstract
We consider studies of therapeutic equivalence. Such studies aim to show that two treatments have similar efficacy. The context is of high importance, and situations in which therapeutic equivalence trials are appropriate are discussed. Choosing an equivalence limit is important to rule out the possibility that a placebo can be considered equivalent to a treatment with benefit. The two one‐sided tests approach is common and uses a Neyman‐Pearson framework for hypothesis testing although the test is commonly conducted by comparing the bounds of a confidence interval to the equivalence limit. Study conduct will be subjected to high scrutiny because poor study conduct can result in the perception of an increased chance of demonstrating equivalence. Some other aspects of a therapeutic equivalence trial are also discussed, including power and choice of an analysis set.
Ministry of Health, Labour and Welfare (
MHLW
, Japan)
Authors: Ono Shunsuke 
Published: December 2007

Abstract
The regulation of clinical trials and new drug approval in Japan is based on the Pharmaceutical Affairs Law (PAL) and related ordinances. The Ministry of Health, Labour and Welfare (MHLW) is the governmental body responsible for enacting legislation for pharmaceutical affairs. The MHLW makes final decisions on whether it should halt trials for which investigational new drugs notifications (INDs) are submitted, and whether it should approve drugs for which New Drug Applications (NDAs) are submitted. The Pharmaceuticals and Medical Devices Agency (PMDA) is a semi‐governmental agency established by law that conducts scientific review of INDs and NDAs via internal review teams. The role of the PMDA as a review agency has become critical in pharmaceutical research and development activities, with recent progress in global regulatory harmonization and the necessity for cooperation between the regulator and the industry. The The PMDA also provides consultation services for clinical development, similar to those by the U.S. Food and Drug Administration. Historically, Japanese regulations have evolved by gradually accepting Western regulatory components into preexisting ones. Although most basic regulatory structures are similar to those in Western countries, there are still some obvious differences, including the applicability of INDs. Facing the recent decline in the numbers of domestic trials, the MHLW has issued several measures to promote domestic trials, including grants to train hospital staffs, but it is not expected that the decline will reverse easily because it is related to a diminishing demand for Japanese trials in response to the globalization of pharmaceutical research and development.
Equivalence Trials and Equivalence Limits
Authors: Hung H. M. James 
Published: December 2007

Abstract
An equivalence trial employs a selected active control treatment as a comparator for evaluating the effect of a test treatment. The notion of equivalence is that the difference between the test treatment and the active control is clinically insignificant with respect to therapeutic benefits or an adverse effect at issue. The threshold of clinical insignificance or indifference must be defined and is often termed “equivalence margin” or “equivalence limit.” In clinical trials, the study question that is more often of primary interest is the noninferiority hypothesis that the test treatment is clinically acceptably inferior to the control. Determination of the noninferiority hypothesis with a specified margin often requires special considerations pertaining to other study objectives, such as showing that the test treatment retains a certain fraction of the control's effect. These special considerations in defining a noninferiority margin may not be applicable to defining the superiority margin in the equivalence hypothesis.
Phase
I
/
II
Clinical Trials
Authors: Zohar Sarah 
Published: December 2007

Abstract
The objective of dose‐finding phase I/II studies is to find an optimal dose level that corresponds to some given acceptable toxicity rate combined with a minimal response rate of a new drug or procedure. Most published phase I/II trials have been designed to determine the maximum tolerated dose during a phase I trial and subsequently to determine the response rate during a phase II trial. Recently, there has been increasing research in the development of dose‐finding methodologies, based on joint modeling of toxicity and efficacy outcomes in the same protocol that aim at minimizing the sample size in case of unacceptable high toxicity or unacceptable low efficacy. The available dose‐finding designs for phase I/II trials are presented with specific regard for new designs that jointly model toxicity and efficacy outcome.
Preference Trials
Authors: Campbell Marion K. , Torgerson David J. 
Published: December 2007

AbstractAlthough the randomized controlled trial is widely accepted as the design of choice for evaluating health‐care interventions, it requires that all participants are prepared to accept allocation to any of the interventions under study. When patients have a strong preference to receive one of the study interventions, this can lead to difficulties with compliance and potentially to biased assessment of outcomes. The patient preference trial has been proposed as a potential solution, with patients with strong preferences being allocated to their treatment of choice and those with no strong preference being randomized in the standard manner. All patients are followed up and outcomes assessed. We discuss the effects of patient preference and review the advantages and disadvantages of the patient preference design.
PhaseIITrials
Authors: Keene Oliver N. 
Published: December 2007

AbstractPhase II trials have two aims:(1)to provide a proof of concept that the drug is able to affect the disease it is designed to affect without overt safety problems and(2)to define the dose(s) to be taken forward to phase III. Trials that specifically address these issues are often referred to as phase IIa and phase IIb trials, respectively. Therefore, phase II trials provide the initial test of efficacy and reassurance on safety in patients and, if successful, define the dose or doses to be carried forward to be studied in the wider populations and longer‐term phase III trials.
Effects of meteorology, astronomical variables, location and human disturbance on the singing apes: Hylobates albibarbis
Authors: Cheyne Susan M. 
Published: December 2007

AbstractGibbons are characterized by their species‐specific calls. The frequency of singing is known to be affected by rainfall, with singing occurring less in the wet season. I investigate the hypothesis that gibbon singing is also affected by the natural light‐dark cycle, and by the changing light intensity and air quality resulting from the smoke haze which blankets the Indonesian island of Borneo on a yearly basis. I compare three singing variables—onset of singing, average duration of singing bout and number of female great calls produced during the dry season of 2006 when there was no smoke haze (June–August) and when there was smoke haze present (September–November). I present evidence which indicates that the changes in singing behavior are affected by changes in rainfall and smoke intensity but not by other meteorological factors (i.e. wind and light intensity) or changing astronomical cues (light intensity, month, time of sunrise, time of moonrise, nocturnal illumination index, day length and night length). The possible long‐term effects of this on gibbon behavior and territoriality are discussed. The need to carry out more research on the long‐term effects of the smoke haze on wildlife behavior and possible solutions to the problem are discussed. Am. J. Primatol. 70:386–392, 2008. © 2007 Wiley‐Liss, Inc.
Synthesis and structural characterization of methacrylic acid/octadecyl acrylate‐graft‐poly(methylhydrosiloxane) by hydrosilylation
Authors: Lin Fang , Song Mizhao , He Zhuangzhi , Zhang Tingyou 
Published: December 2007

AbstractMethylmethacrylate (MMA) and octadecyl acrylate (OA) were grafted to poly(methylhydrosiloxane) (PMHS) by hydrosilylation, respectively, with hexachloroplatinic acid as catalyst, and the former was further hydrolyzed to prepare methacrylic acid (MAA)‐graft‐PMHS under the alkaline condition. Through orthogonal experiment, main factors affecting the graft reaction between OA and PMHS were discussed and arranged in a decreasing order according to their abilities of the effect on the hydrosilylation of OA with PMHS: catalyst dosage, reaction temperature, reaction time, material ratio, and solvent dosage. It was found that the hydrosilylation of OA with PMHS was easier to that of MMA with PMHS. Under optimal conditions, the grafting ratios of MMA with PMHS and OA with PMHS reached about 90 and 95%, respectively. FTIR and 1H NMR spectra indicated that the hydrosilylation reactions followed the Markovnikov's rule and played a strong preference toward β‐1,2‐addition. The test of contact angle indicated that surface energy of a system was mainly dependent on the polar groups. The surface energy of OA‐graft‐PMHS (35.07 mN/m) was similar to those of PMHS (35.62 mN/m) and polyoctadecyl acrylate (36.57 mN/m), and lower than that of MAA‐graft‐PMHS (43.50 mN/m). © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2008
Conjugate electrospinning of continuous nanofiber yarn of poly(L‐lactide)/nanotricalcium phosphate nanocomposite
Authors: Li Xinsong , Yao Chen , Sun Fuqian , Song Tangying , Li Yunhui , Pu Yuepu 
Published: December 2007

AbstractThe continuous nanofiber yarns of poly(L‐lactide) (PLLA)/nano‐β‐tricalcium phosphate (n‐TCP) composite are prepared from oppositely charged electrospun nanofibers by conjugate electrospinning with coupled spinnerets. The morphology and mechanical properties of PLLA/n‐TCP nanofiber yarns are characterized by scanning electron microscope, transmission electron microscope, and electronic fiber strength tester. The results show that PLLA/n‐TCP nanofibers are aligned well along the longitudinal axis of the yarn, and the concentration of PLLA plays a significant role on the diameter of the nanofibers. The thicker yarn of PLLA/n‐TCP composite with the weight ratio of 10/1 has been produced by multiple conjugate electrospinning using three pairs of spinnerets, and the yarn has tensile strength of 0.31cN/dtex. A preliminary study of cell biocompatibility suggests that PLLA/n‐TCP nanofiber yarns may be useable scaffold materials. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2008
Prominent down‐regulation of storage protein genes after bacterial challenge in eri‐silkworm, Samia cynthia ricini
Authors: Meng Yan , Omuro Naoko , Funaguma Shunsuke , Daimon Takaaki , Kawaoka Shinpei , Katsuma Susumu , Shimada Toru 
Published: December 2007

AbstractWe constructed two independent cDNA libraries from the fat body of Escherichia coli‐ or Candida albicans‐challenged eri‐silkworm Samia cynthia ricini larvae. We performed comparative expressed sequence tag (EST) analysis of the two cDNA libraries and found that two putative storage protein genes, ScSP1 and ScSP2, were markedly repressed by E. coli injection as compared with C. albicans injection. By quantitative real‐time RT‐PCR analysis, we showed that ScSP1 mRNA significantly reduced to 1/32–1/3 in the fat body of the female larvae, and ScSP2 mRNA reduced to 1/7–1/3 and 1/22–1/5 in the females and males, respectively, 12–36 h after E. coli injection as compared with PBS injection. In addition, SDS‐PAGE analysis revealed that the accumulation of both the ScSP proteins in the larval hemolymph apparently decreased up to 36 h after E. coli injection. However, the amounts of the two ScSP proteins returned to the same level as those in the larvae injected with PBS by 48 h after injection, showing that the reduction in ScSPs caused by the bacterial challenge was transient. Moreover, potential binding sites for the Drosophila Rel/NF‐κB protein Dorsal were found in the 5′ upstream regulatory regions of ScSP1 and ScSP2, suggesting the participation of the Rel/NF‐κB proteins in controlling the bacterial suppression of the ScSP genes. These results suggested the hypothesis that S. c. ricini has a genetic program to shut down temporarily dispensable gene expression in order to induce an acute and efficient expression of immune‐related genes. These findings may provide new insight into the innate immune system in lepidopteran insects. Arch. Insect Biochem. Physiol. 2007. © 2007 Wiley‐Liss, Inc.
Electromagnetic millimeter wave induced hypoalgesia: Frequency dependence and involvement of endogenous opioids
Authors: Radzievsky A.A. , Gordiienko O.V. , Alekseev S. , Szabo I. , Cowan A. , Ziskin M.C. 
Published: December 2007

AbstractMillimeter wave treatment (MMWT) is based on the systemic biological effects that develop following local skin exposure to low power electromagnetic waves in the millimeter range. In the present set of experiments, the hypoalgesic effect of this treatment was analyzed in mice. The murine nose area was exposed to MMW of “therapeutic” frequencies: 42.25, 53.57, and 61.22 GHz. MMWT‐induced hypoalgesia was shown to be frequency dependent in two experimental models: (1) the cold water tail‐flick test (chronic non‐neuropathic pain), and (2) the wire surface test (chronic neuropathic pain following unilateral constriction injury to the sciatic nerve). Maximum hypoalgesic effect was obtained when the frequency was 61.22 GHz. Other exposure parameters were: incident power density = 13.3 mW/cm2, duration of each exposure = 15 min. Involvement of δ and κ endogenous opioids in the MMWT‐induced hypoalgesia was demonstrated using selective blockers of δ‐ and κ‐opioid receptors and the direct ELISA measurement of endogenous opioids in CNS tissue. Possible mechanisms of the effect and the perspectives of the clinical application of MMWT are discussed. Bioelectromagnetics 29:284–295, 2008. © 2007 Wiley‐Liss, Inc.
Yield optimization of regulated metabolic systems using deterministic branch‐and‐reduce methods
Authors: Polisetty Pradeep K. , Gatzke Edward P. , Voit Eberhard O. 
Published: December 2007

AbstractThis paper addresses product yield optimization in microorganisms grown in continuous culture. Traditional optimization strategies of random mutagenesis and selection will eventually have limited efficacy, thus requiring more focused strategies. The best candidates for such strategies appear to be mathematical models that capture the essence of metabolic systems and permit optimization with computational methods. In the past, models used for this purpose have been stoichiometric, kinetic in the form of S‐systems, or ad hoc. This work presents a deterministic approach based on generalized mass action (GMA) systems. These systems are interesting in that they allow direct merging of stoichiometric and S‐system models. Two illustrations are considered. In the first case, the fermentation pathway in Saccharomyces cerevisiae is optimized for ethanol production under steady‐state conditions. The model of this pathway is relatively small, with five states and eight rate constants. The second example addresses the maximization of citric acid in the mold Aspergillus niger. For the optimization of this larger pathway system with 30 states and 60 reactions, a Mixed Integer Nonlinear Programming (MINLP) is proposed. It is shown that efficient MINLP algorithms, based on convexification, branch‐and‐reduce methods, and binary variable selection, are essential for solving these difficult optimization problems. Biotechnol. Bioeng. 2008;99: 1154–1169. © 2007 Wiley Periodicals, Inc.
Regio‐ and Stereoselective Ring‐Opening Reactions of Epoxides with Indoles and Pyrroles in 2,2,2‐Trifluoroethanol
Authors: Westermaier Martin , Mayr Herbert 
Published: December 2007

AbstractAliphatic and aromatic epoxides react regio‐ and stereoselectively with indoles and pyrroles in 2,2,2‐trifluoroethanol without the use of a catalyst or any other additive. While aromatic epoxides are selectively attacked at the benzylic position, aliphatic epoxides react at the less‐substituted position. Chiral epoxides react with >99 % ee (ee=enantiomeric excess).
Infrared Study of Intercomponent Interactions in a Switchable Hydrogen‐Bonded Rotaxane
Authors: Jagesar Dhiredj C. , Hartl František , Buma Wybren Jan , Brouwer Albert M. 
Published: December 2007

AbstractThe macrocycle in rotaxane 1 is preferentially hydrogen bonded to the succinamide station in the neutral form, but can be moved to the naphthalimide station by one‐electron reduction of the latter. The hydrogen bonding between the amide NH groups of the macrocycle and the CO groups in the binding stations in the thread was studied with IR spectroscopy in different solvents in both states. In addition, the solvent effect on the vibrational frequencies was analyzed; a correlation with the solvent acceptor number (AN) was observed. The conformational switching upon reduction could be detected by monitoring the hydrogen‐bond‐induced shifts of the ν(CO) frequencies of the CO groups of the succinamide and the reduced naphthalimide stations. The macrocycle was found to shield the encapsulated station from the solvent: wavenumbers of ν(CO) bands of the CO groups residing inside the macrocycle cavity remain unaffected by the solvent polarity.
Electronic Structure, Galvanomagnetic and Magnetic Properties of the Bismuth Subhalides Bi4I4 and Bi4Br4.
Authors: Filatova T. G. , Gurin P. V. , Kloo L. , Kulbachinskii V. A. , Kuznetsov A. N. , Kytin V. G. , Lindsjo M. , Popovkin B. A. 
Published: December 2007

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Generation of One Light‐Induced Metastable Nitrosyl Linkage Isomer in [Pt(NH3)4Cl(NO)]Cl2 in the Red Spectral Range.
Authors: Schaniel Dominik , Woike Theo , Delley Bernard , Biner Daniel , Kraemer Karl W. , Guedel Hans‐Ueli 
Published: December 2007

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis and Single‐Crystal X‐Ray Diffraction Studies of New Framework Substituted Type II Clathrates, Cs8Na16AgxGe136‐x (x < 7).
Authors: Beekman M. , Wong‐Ng W. , Kaduk J. A. , Shapiro A. , Nolas G. S. 
Published: December 2007

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis of a New Series of Chiral Tri‐ and Tetradentate Ligands and Their Application in Titanium‐Catalyzed Pinacol Coupling Reaction.
Authors: Chatterjee A. , Joshi N. N. 
Published: December 2007

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Thia‐Michael Addition Reactions in Water Using 3‐[Bis(alkylthio)methylene]pentane‐2,4‐diones as Odorless and Efficient Thiol Equivalents.
Authors: Chai Yanyan , Dong Dewen , Ouyang Yan , Liang Yongjiu , Wang Yan , Li Minghui , Liu Qun 
Published: December 2007

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
A Facile Microwave‐Assisted Synthesis of p‐Quinols by Lead(IV) Acetate Oxidation.
Authors: Prokai‐Tatrai Katalin , Rivera‐Portalatin Nilka M. , Rauniyar Navin , Prokai Laszlo 
Published: December 2007

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis of New Amino Acids with a 5‐Imino‐2,5‐dihydro‐3‐furanyl Substituent at the Amino Group.
Authors: Trofimov Boris A. , Mal'kina Anastasiya G. , Shemyakina Olesya A. , Borisova Angela P. , Nosyreva Valentian V. , Dyachenko Oleg A. , Kazheva Olga N. , Alexandrov Gennadii G. 
Published: December 2007

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
A Simple One‐Pot Synthesis of 3‐Alkoxy‐3‐cyanocarboxylic Acids: A Rapid Entry to New GABA Derivatives.
Authors: Zanatta Nilo , da Silva Fabio M. , da Rosa Luciana S. , Jank Louise , Bonacorso Helio G. , Martins Marcos A. P. 
Published: December 2007

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.