bluuebunny/crossref_metadata_2025_split huggingface dataset:
Block Randomization
Authors: McEntegart Damian 
Published: May 2013

Abstract
Simple unconstrained randomization is the yardstick for randomization techniques in clinical trials as it is completely unpredictable and provides an unambiguous basis for inference from statistical analysis. But simple randomization is rarely used because of the need to protect the trial from imbalance in the overall numbers allocated to treatment and from temporal bias in the allocations. For these reasons the randomization procedure is often restricted by some form of blocking, the most common being random permuted blocks. The methodology, issues and practical considerations relating to the use of blocked randomization are described. Particular attention is paid to the issue of potential selection bias, which may arise from the predictability of tail allocations towards the end of any block of treatment allocations if the past allocations in the block are known or can be guessed. The merits of using unequally sized blocks to avoid selection bias are discussed in detail. Inference following blocked randomization is also discussed. Alternative forms of blocking are described; these include lists generated from the maximal procedure, the use of rows from Hadamard matrices, Zelen's balanced blocks procedure and mixed randomization. Practical considerations relating to the use of blocked randomization are described including software used to generate random blocks. Also covered are considerations relating to the use of electronic systems to automatically perform allocation from a pre‐defined randomization list; the use of such systems is becoming increasingly common with the advent of telephone interactive voice response (IVR) and web based randomization systems.
Coronary Drug Project
Authors: Canner Paul L. 
Published: May 2013

AbstractThe Coronary Drug Project, which was conducted during 1966 to 1974, was a randomized, double‐blind, placebo‐controlled trial of five lipid‐modifying agents—estrogens at two dosage levels, dextrothyroxine, clofibrate, and niacin—in 8341 men with previous myocardial infarction. The primary efficacy outcome was all‐cause mortality for the entire follow‐up period. The first three named regimens were terminated early because of adverse effects. Only niacin significantly reduced the risk of (1) cardiovascular events during a mean follow‐up of 6.2 years and (2) all‐cause mortality during 6.2 years with study treatment plus an additional 9 years of post‐trial follow‐up. Analyses of treatment–placebo differences with respect to all‐cause mortality, subdivided by level of adherence to the study prescription and by amount of change in serum cholesterol level, could not be properly interpreted because reasons for good/poor adherence and for cholesterol changes in the placebo group were not well defined.
Dose Ranging Crossover Designs
Authors: Patterson Scott D. , Jones Byron , Zariffa Névine 
Published: May 2013

Abstract
Dose ranging trials are used frequently in drug development to learn about dose response for both desirable and undesirable effects and to provide sponsors with confidence that investment in confirmatory trials for market access is likely to be successful. The design of crossover studies and analysis of data that develops from such crossover trials are discussed.
Futility Analysis
Authors: Freidlin Boris 
Published: May 2013

AbstractMost randomized clinical trials are designed to demonstrate benefit of experimental versus standard treatment. For ethical and economic reasons, it is important to stop a trial early for “futility” if there is no longer a reasonable chance that the experimental arm can be shown to be definitively better than the standard arm. Futility monitoring has become a widely accepted component of clinical trial methodology. We provide a review of commonly used futility procedures and discuss practical aspects of their implementation.
Gene Therapy
Authors: Ginn Samantha L , Alexander Ian E 
Published: May 2013

Abstract
Conducting a clinical trial poses a unique set of challenges that must be addressed to ensure the safety of human subjects. In this article, we discuss issues that relate in particular to gene therapy clinical trials. These issues include the choice of gene delivery system, the need for extensive preclinical testing to ensure the feasibility and safety of the approach, and careful monitoring of subjects for short‐ and long‐term toxicity associated with the gene transfer protocol.
Kaplan–Meier Plot
Authors: Holländer Norbert 
Published: May 2013

AbstractThe Kaplan–Meier plot or Kaplan–Meier curve is the standard method to describe and compare graphically the overall survival of groups of patients. This method is applied to survival time, which is defined as time from treatment start or date of randomization to death or last date of follow up, and, more general, to any type of time‐to‐event data, such as time‐to‐disease progression, time‐to‐detoriation, or time‐to‐first toxicity. Sometimes, the time‐to‐event is also called failure time. In the sequel, the term “survival time” is used as a synonym for any time‐to‐event.
Longitudinal Data
Authors: Li Hung‐Ir 
Published: May 2013

Abstract
Longitudinal data have been the focus in various research such as economy, social science, public health, and biomedical research in the past few decades. These data comprise outcome measures or responses prospectively collected or naturally accrued repeatedly from the same subjects across multiple time points along with subject characteristic measures. In some observational studies in epidemiology/public heath, the data accrued over a long period of time as recorded in medical charts and are retrospectively retrieved. The data are used to answer questions regarding the change or progression of the disease over time and/or potential risk factors for the disease. Although in other studies, the existing data could be used to identify subgroups with different background characteristics or traits. The identified groups are then followed up for their health conditions for a certain period of time prospectively. The data from these groups are then compared with answer questions set out for the studies. In the clinical research and development settings, most of the longitudinal data are collected via prospectively designed clinical trials in order to assess the changes in efficacy and/or safety of certain medical intervention, drug, biologics, or devices. The longitudinal data from clinical trials in phase III of product development are intended to confirm that the clinical benefit or desired changes over time are primarily due to the target product, can be maintained for an adequate amount of time, and are applicable to a well‐defined population before regulatory approval is granted and the product is registered for public use. This article provides a summary of the definitions, features, and various types of longitudinal data resulting from clinical trials in phase III medicinal product development. The respective characteristics and the related issues along with the rules of thumb in the selection of the statistical methods for the analyses will also be provided.
Non‐Inferiority Trial
Authors: Hung H. M. James , Wang Sue‐Jane , O'Neill Robert 
Published: May 2013

Abstract
Noninferiority trials employ a selected active‐control treatment, the effect of which has been established in historical placebo‐controlled trials. The active control serves as a comparator for evaluating the effect of an experimental treatment. A placebo arm may be either present in or absent from the noninferiority trial, depending on whether use of the placebo arm is feasible. In contrast with showing superiority, it is much more challenging to design a “show noninferiority” trial. The notion of noninferiority is extremely difficult to define, and a threshold termed “noninferiority margin” must be determined to define the noninferiority hypothesis for testing. The margin determination depends on many key factors: the objective of the noninferiority trial, critical assumptions pertaining to the ability of a trial to distinguish between an effective and an ineffective treatments, and the applicability of the historical estimate of the active control's effect to the noninferiority trial when the placebo cannot be used, and so forth. This article is intended to pinpoint the factors critically needing consideration for the viability of using a noninferiority trial to evaluate the effect of an experimental treatment.
Placebos
Authors: Holbrook Anne , Goldsmith Charles H. , Leung Mova 
Published: May 2013

AbstractPlacebos have a long and controversial history in clinical research and in practice. In this chapter, we review the meaning, the pharmacology, effectiveness, safety, influences on, and ethical issues involving placebos. Various international guidelines for the use of placebos in research are available and evolving. We then suggest novel factorial designs to allow a full assessment of efficacy and safety of a new therapy while minimizing patient exposure to placebo alone.
Treatment Interruption
Authors: Grund Birgit 
Published: May 2013

AbstractInterruption of active drug treatment in clinical trials can be classified broadly as therapeutic treatment interruption (TI), in which the potential therapeutic benefit of supervised interruption of treatment is investigated, and analytic TI, in which participants are randomized to stopping versus continuing active treatment; the TI arm serves as control group. Design issues for therapeutic TI trials are discussed in the example of a trial in HIV/AIDS.Analytic TIs are used in therapeutic HIV vaccine trials, in randomized discontinuation designs, and in other situations. The use of a randomized discontinuation design for a Phase II drug trial in cancer is discussed.
Rotifera
Authors: Wallace Robert Lee , Smith Hilary April 
Published: May 2013

Abstract

Rotifera is a moderately sized phylum of minute, bilaterally symmetrical, unsegmented animals that live predominantly in freshwaters. The phylum name (Latin,
rota
, wheel;
ferre
, to bear), first used by Cuvier in 1798, refers to the anterior end that in many species resembles a rotating wheel due to the sequential beat of its cilia. Rotifers have been found on every continent, occupying a diverse array of habitats, including marine, brackish and freshwaters, as well as the film of water that coats terrestrial mosses and particles in damp soils. In lakes rotifers often achieve high population densities (>1000 individuals per litre); thus, as consumers of bacteria, algae and protists they are ecologically important in transferring energy to higher trophic levels. As rotifers are a good food for young fishes, they are grown in mass quantities in commercial aquaculture. They also serve as models for research on ageing, and as bioindicators for ecotoxicology.

Key Concepts:

Rotifers have been found in the inland waters (both fresh and saline) of every continent, in the moisture covering some plants such as mosses, and in damp soil. Although generally not as abundant as in continental waters, rotifers often flourish in nearshore marine waters and estuaries.

Many rotifers are capable of undergoing dormancy, either as adults or embryos, allowing them to disperse in space or time and often avoid harsh conditions.

Feeding mainly on other microscopic organisms, including bacteria, algae and protists, rotifers are important basal consumers in aquatic systems.

In certain lakes, rotifers play an important role connecting the microbial loop to the classic food web, whereby the dissolved organic carbon is taken up by the bacteria that are consumed by rotifers, which in turn are consumed by higher trophic levels. In this way, a portion of the energy in dissolved organic matter is returned to the food web.

As they are the first food for larval organisms, rotifers have been exploited by aquaculturists to maintain commercially important fishes, shrimps and crabs.

As they are comparatively inexpensive and easy to culture and possess relatively short life spans, rotifers are used in ageing studies and to assess the toxicity of compounds such as heavy metals, pesticides and pharmaceuticals.

Some species of rotifers have specific ecological requirements making them useful as indicators of water quality.

The phylogenetic position of rotifers has not yet been resolved, but they appear to be related to a group of small, jawed metazoans (Gnathifera). Acanthocephala, an entirely parasitic phylum, are now considered to be highly aberrant rotifers.

Over the years rotifers have entered the collective culture ethos as subjects of poetry, science fiction and children's literature, artists' workings in glass and mixed media and pop music.
Entoprocta
Authors: Nielsen Claus 
Published: May 2013

Abstract

The Entoprocta are a small phylum of minute, solitary or colonial, sessile, aquatic animals. Approximately 200 species have been described worldwide, with only 1 species occurring in freshwater. The colonial species encrust stones, shells and algae. The solitary species are almost always less than one millimetre long; the individuals in the colonial species may reach several millimetres. Each individual consists of a globular body with a crown of tentacles around a concave, ventral area and a cylindrical stalk. The ciliated tentacles create a water current between the tentacles and away from the mouth. Food particles are captured from this current by compound cilia on the lateral sides of the tentacles. The solitary species are mostly associated with water‐current‐producing hosts, such as polychaetes, sponges and bryozoans; these species are not conspicuous and most of the reported distributions reflect specialists’ searches. Development is indirect with more or less typical trochophora larvae.

Key Concepts:

Entoprocts are small solitary or colonial aquatic organisms.

The colonial species grow on stones, shells or algae, whereas most of the solitary species are associated with other marine invertebrates, especially polychaetes and sponges.

Entoprocts are filter feeders that capture plankton particles with compound cilia on a horseshoe of tentacles.

Sexual reproduction is through spiral cleavage and trochophora larvae, which either settle and go through a metamorphosis or develop buds which detach from the larval body.

Asexual reproduction is through budding from the frontal side of the body in the solitary species and through budding from stolons or a basal plate in the colonial species.
Yeast (
YAC
) and Human (
HAC
) Artificial Chromosome Clones
Authors: Nagaraja Ramaiah , Kouprina Natalay , Larionov Vladimir , Schlessinger David 
Published: May 2013

Abstract

Artificial chromosome vector systems in yeast and bacteria have facilitated the increasingly rapid pace of mapping and sequencing of complex genomes. Traditional bacterial cloning systems have remained important for the study of relatively short clones, but for the cloning of very large
deoxyribonucleic acid (DNA)
segments yeast artificial chromosomes (YACs) have completely replaced earlier bacterial systems, including lambda phage‐based cosmids. YACs comprise cloned DNA fragments ranging from 50 kb to more than 1 million base pairs, along with sequences that render them capable of growth in yeast or bacteria. YACs provide the additional advantage of permitting direct isolation of a targeted genomic region as a circular molecule from complex genomes by transformation‐associated recombination. Moreover, YAC cloning has allowed the propagation of large tandem repeat arrays and entire bacterial genomes. By taking advantage of the efficient yeast recombination system, YAC clones can be further modified and used for functional studies of full‐length genes and for the study of huge centromeric DNA repeat regions that are not yet analysed or included in the genome assemblies of human and other organisms.

Key Concepts:

Basic structure of vectors used in the construction of artificial chromosomes that can replicate in yeast, bacteria and human cells.

Utilities of artificial chromosomes.

Isolation of complete genes and large DNA segments, including repetitive chromosomal regions.

Targeted recombination‐based cloning of genes and highly repetitive regions.

Reconstruction of large DNA regions by recombination among multiple YAC clones.
Chlorophyll‐Binding Proteins
Authors: Lokstein Heiko , Grimm Bernhard 
Published: May 2013

Abstract

Chlorophylls and bacteriochlorophylls are the dominant pigments on Earth and serve – noncovalently bound to specific proteins – as principal light‐harvesting as well as energy‐transforming cofactors in photosynthetic organisms. The major groups of (bacterio)chlorophyll‐binding proteins are the photosynthetic reaction centres (RCs) and the associated light‐harvesting (antenna) complexes. Other proteins include water‐soluble chlorophyll‐binding proteins as well the chlorophyll biosynthetic and degrading enzymes. Although all RCs show structural homologies and appear to have evolved from a common ancestor, light‐harvesting antenna designs vary considerably. The enormous progress that has been achieved in the elucidation of structures and functions of chlorophyll‐binding proteins is reviewed. It has become increasingly clear that light‐harvesting complexes do not only serve to enlarge the absorption cross‐sections of the RCs but are important in the adaptation of the photosynthetic apparatus and regulation of the energy‐transforming processes in response to environmental and endogenous conditions.

Key Concepts:

Chlorophylls and bacteriochlorophylls serve – noncovalently bound to specific proteins – as principal energy‐transforming cofactors in photosynthesis.

Light‐harvesting antenna complexes ensure optimised light harvesting and transfer of excitation energy to the reaction centres of the photosystems.

Reaction centre proteins remained fairly conserved during evolution, whereas photosynthetic organisms developed many distinct forms of light‐harvesting complexes.

Oxygenic photosynthesis evolved to two different photosystems that have most likely emerged from a common ancestor.

The antenna system of plants and algae can ‘switch’ from effective light harvesting to photoprotective excess excitation dissipation to prevent photo‐oxidative damage.
Epigenetics of Obesity and Diabetes
Authors: Sheen Jean‐Ju , Heo Hye J , Einstein Francine H 
Published: May 2013

Abstract

The unprecedented rise in the number of people who are obese and/or diabetic poses increasing demands on healthcare worldwide. Current research is turning towards factors other than genotype that may predispose people to such diseases. The sum total of lifetime environmental exposures, the exposome, combines with
deoxyribonucleic acid
sequences to influence phenotypic expression. The epigenome, or the chemical processes that alter gene expression without changing the underlying genetic sequence, is at the interface of the genome and exposome. Early epigenetic influences may cause a predisposition for adult diseases such as obesity and diabetes. Limited human studies, complemented by animal studies, have demonstrated that

in utero

‘programming’ may alter adult metabolic profiles. New technologies, such as layered omics, may provide tools that will allow predictions for disease susceptibility, and may be crucial for the early prevention and treatment of obesity and diabetes.

Key Concepts:

The exposome complements the genome in its influence of phenotypic expression.

The epigenome is at the interface of the genome and the exposome.

The hypothesis of the fetal origins of adult disease may describe early epigenetic influences for adult diseases such as obesity and diabetes.

Animal studies have demonstrated that
in utero
‘programming’ may alter adult metabolic profiles.

Layered omic technologies may be the tool that will allow predictions for disease susceptibility, which will be crucial to early prevention/treatment for disease epidemics such as diabetes and obesity.
Sodium Storage and Transport Properties in Layered Na2Ti3O7 for Room‐Temperature Sodium‐Ion Batteries
Authors: Pan Huilin , Lu Xia , Yu Xiqian , Hu Yong‐Sheng , Li Hong , Yang Xiao‐Qing , Chen Liquan 
Published: May 2013

AbstractLayered sodium titanium oxide, Na2Ti3O7, is synthesized by a solid‐state reaction method as a potential anode for sodium‐ion batteries. Through optimization of the electrolyte and binder, the microsized Na2Ti3O7 electrode delivers a reversible capacity of 188 mA h g−1 in 1 M NaFSI/PC electrolyte at a current rate of 0.1C in a voltage range of 0.0–3.0 V, with sodium alginate as binder. The average Na storage voltage plateau is found at ca. 0.3 V vs. Na+/Na, in good agreement with a first‐principles prediction of 0.35 V. The Na storage properties in Na2Ti3O7 are investigated from thermodynamic and kinetic aspects. By reducing particle size, the nanosized Na2Ti3O7 exhibits much higher capacity, but still with unsatisfied cyclic properties. The solid‐state interphase layer on Na2Ti3O7 electrode is analyzed. A zero‐current overpotential related to thermodynamic factors is observed for both nano‐ and microsized Na2Ti3O7. The electronic structure, Na+ ion transport and conductivity are investigated by the combination of first‐principles calculation and electrochemical characterizations. On the basis of the vacancy‐hopping mechanism, a quasi‐3D energy favorable trajectory is proposed for Na2Ti3O7. The Na+ ions diffuse between the TiO6 octahedron layers with pretty low activation energy of 0.186 eV.
High dielectric constant polyaniline/sulfonated poly(aryl ether ketone) composite membranes with good thermal and mechanical properties
Authors: Zhang Yunhe , Huo Pengfei , Liu Xiao , Rong Changru , Wang Guibin 
Published: May 2013

ABSTRACTAll‐organic polyaniline (PANI)/sulfonated poly(aryl ether ketone) (SPAEK) composite membranes consisting of a PANI (conducting) filler evenly distributed in an SPAEK (insulating) matrix were prepared with a solution‐blending technique. The dielectric properties, electrical conductivity, and thermal and mechanical performances of the all‐organic PANI/SPAEK composite membranes were investigated as a function of different PANI loading levels. The composite membrane containing 30 wt % PANI exhibited a high dielectric constant of about 600, a low dielectric loss tangent of about 0.6 (at 1 kHz), and good thermal properties (temperature for 5% weight loss > 250°C) and mechanical properties (tensile strength ≈ 35 MPa). © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1990–1995, 2013
Electric Double‐Layer Capacitor Based on an Ionic Clathrate Hydrate
Authors: Lee Wonhee , Kwon Minchul , Park Seongmin , Lim Dongwook , Cha Jong‐Ho , Lee Huen 
Published: May 2013

AbstractHerein, we suggest a new approach to an electric double‐layer capacitor (EDLC) that is based on a proton‐conducting ionic clathrate hydrate (ICH). The ice‐like structures of clathrate hydrates, which are comprised of host water molecules and guest ions, make them suitable for applications in EDLC electrolytes, owing to their high proton conductivities and thermal stabilities. The carbon materials in the ICH Me4NOH⋅5 H2O show a high specific capacitance, reversible charge–discharge behavior, and a long cycle life. The ionic‐hydrate complex provides the following advantages in comparison with conventional aqueous and polymer electrolytes: 1) The ICH does not cause leakage problems under normal EDLC operating conditions. 2) The hydrate material can be utilized itself, without requiring any pre‐treatments or activation for proton conduction, thus shortening the preparation procedure of the EDLC. 3) The crystallization of the ICH makes it possible to tailor practical EDLC dimensions because of its fluidity as a liquid hydrate. 4) The hydrate solid electrolyte exhibits more‐favorable electrochemical stability than aqueous and polymer electrolytes. Therefore, ICH materials are expected to find practical applications in versatile energy devices that incorporate electrochemical systems.