bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioavailability and Bioequivalence
Authors: Chow Shein‐Chung
Published: September 2015

Bioavailability is referred to as the rate and extent to which the active drug ingredient or active moiety from the drug product is absorbed and becomes available at the site of drug action. The relative bioavailability in terms of the rate and extent of drug absorption is considered predictive of clinical outcomes. In 1984, the United States Food and Drug Administration (FDA) was authorized to approve generic drug products under the Drug Price Competition and Patent Term Restoration Act based on evidence of average bioequivalence in drug absorption through the conduct of bioavailability and bioequivalence studies. This entry provides an overview of definition of bioavailability and bioequivalence, Fundamental Bioequivalence Assumption, regulatory requirements, and process for bioequivalence assessment of generic drug products. Basic considerations including criteria, study design, power analysis for sample size determination, and the conduct of bioequivalence trial, and statistical methods are provided. Practical issues such as scaled average criteria for assessment of highly variable drug products and sample size calculation for higher‐order crossover designs are also discussed.
Bayes Linear Analysis
Authors: Goldstein Michael
Published: September 2015

The Bayes linear approach is concerned with problems in which we want to combine prior judgments of uncertainty with observational data, and we use expected value rather than probability as the primitive for expressing these judgments. This distinction is of particular relevance in problems with too many sources of information for us to be comfortable in making a meaningful full joint prior probability specification of the type required for Bayesian inference. For such problems, the Bayes linear approach is similar in spirit to a full Bayesian analysis but offers a practical methodology for analyzing partially specified beliefs for large problems. We describe the adjustment of prior means and variances given data and explain the various interpretations that we may attribute to such adjustments. We describe the interpretive and diagnostic cycle for the analysis: (i) we interpret the expected effects of the adjustment, a priori; (ii) given observations, we interpret the outcome of the actual adjustment; (iii) we make diagnostic comparisons between observed and expected beliefs. The approach to modeling and analysis through the second‐order exchangeability representation theorem is described, and various real world applications are discussed.
Probit Models,
B
ayesian Analysis of
Authors: Albert James H. , Chib Siddhartha
Published: September 2015

This article reviews the Albert and Chib (1993) data augmentation approach in the implementation of a Markov chain Monte Carlo algorithm for regression with a binary response variable. The article provides a review of the extensions in the original Albert and Chib paper and the wide range of applications and extensions in the literature using this approach.
Surrogate Markers
Authors: Molenberghs Geert
Published: September 2015

The rationale of using surrogate endpoints in clinical studies is discussed, along with the need for proper evaluation of candidate surrogates. After sketching the single‐trial framework, and the issues surrounding it, a meta‐analytic framework is presented. This is done first for continuous outcomes, where after various outcome types are discussed. Special attention is given to longitudinal outcomes. The need for unification across a variety of surrogacy evaluation measures is discussed, and a unified framework is presented. Connections amon the meta‐analytic, association‐based framework, and its causal counterpart are sketched. Implications for the design of clinical trials are put forward.
Nonstandard Multivariate Tests
Authors: Follmann Dean
Published: September 2015

Standard approaches for testing whether a multivariate normal mean vector is zero are agnostic regarding alternative hypothesis. In some settings, subject‐matter considerations will imply structure on the alternative of the mean vector, for example, that each element of the mean vector is positive, or that the elements are monotonically increasing. Nonstandard multivariate tests incorporate this knowledge about the alternative hypothesis to derive more powerful tests. This article provides a brief overview of selected nonstandard multivariate tests.
Multivariate Analysis
Authors: Johnson Richard A. , Wichern Dean
Published: September 2015

Multivariate analysis is the body of statistical methodology used to analyze simultaneous measurements on several variables. We provide an overview of important methods for making inferences about mean vectors, analyzing covariance structure, and classifying and grouping items. In addition, there is a brief introduction to procedures for creating lower‐dimensional representations of items and/or variables. References and a list of sources for further reading are provided.
Quality Concept for Official Statistics
Authors: Elvers Eva , Lindén Håkan
Published: September 2015

The quality concept that is defined refers to the statistical output. The view taken is that quality of statistics refers to all aspects of how well statistics meet users' needs and expectations of statistical information. Hence, the quality concept should list all aspects that are implicit in this broad definition of quality of statistics. This means that the producer of the statistics should provide neutral descriptive information about the quality components – even if it is an inherent challenge to obtain quantitative measures for some of them. The assessment of the quality of the statistics should be left to the users for their particular uses. The quality concept is useful in communication with users about needs and priorities, and naturally also for design, planning, and evaluation of statistical production processes. Even if the quality concept focuses on official statistics, the concept may be used more broadly. This article presents the quality concept, the challenges faced, and new lines of enquiry.
Risk Analysis, Extremes in
Authors: Teugels Jozef L.
Published: September 2015

We continue a previous contribution of extremal thinking with special emphasis to risk analysis. After dealing with recent advances in probabilistic and statistical aspects of extreme value theory (EVT), we deal with extreme value problems within the context of stochastic processes. We finish by focusing on a couple of specific questions and a number of applications. A comprehensive list of references is included.
Under‐ and Overdispersion
Authors: Xekalaki Evdokia
Published: September 2015

A synopsis of probability models for over‐ and underdispersion is provided, looking at their origins, motivation, first main contributions, important milestones, and applications. As the field of accident studies has received much attention, and various theories have been developed for the interpretation of factors underlying an accident situation, most of the models will be presented in accident or actuarial contexts. Of course, with appropriate parameter interpretations, the results are adaptable in a great variety of other situations in fields ranging from economics, inventory control, and insurance through to demometry, biometry, psychometry, and web access modeling.
Capture‐Recapture for Human Populations
Authors: Chao Anne
Published: September 2015

Capture–recapture methods, originally developed for estimating demographic parameters of animal populations, have been applied to human populations. In epidemiology and health sciences, most surveillance studies and prevalence surveys based on multiple records of incomplete lists are likely to miss some cases, and thus the number of ascertained cases in the final merged list tends to undercount the true size of the target population. Capture–recapture methods can be applied for these types of studies/surveys to provide useful estimators for the size of the target population and adjust for underascertainment. This article describes the history of the method and focuses on population size estimation based on the sample‐coverage approach, which also provides measures to quantify the extent of overlapping information and assess the dependences among samples. The R packageCARE1(CApture–REcapture, part 1) is applied to two real examples for illustration. Other models are briefly discussed.
Bayesian Methods in Clinical Trials
Authors: Ashby Deborah
Published: September 2015

A clinical trial is an experiment carried out to gain knowledge about the relative benefits of two or more treatments. Typically, this is part of a gradual accrual of knowledge. The concept of updating of beliefs or evidence is the essence of Bayesian statistics. This article explains the essential concepts through a simple example, and then discusses some of the issues raised, namely, the legitimate sources of previous beliefs or evidence, including the question of subjectivity, and implications for the design of trials and Bayesian reporting of clinical trials. A particular area of application is data monitoring. Most of the discussion is in the context of two‐group parallel trials with straightforward analyses, but the framework is completely general, and applies to more complex designs and analyses. For the combination of results of several trials, possibly with other evidence, Bayesian meta‐analysis is outlined. Clinical trials are often used as part of wider decision‐making processes. Bayesian statistics is sometimes set in the context of decision making, and the implications of this are discussed.
Growth and Development
Authors: Cole T. J.
Published: September 2015

Growth and development is the process through which the fetus changes in size, shape, composition, and function to become a reproductively mature adult. Growth is generally defined as the change (or rate of change) in one or more continuous measures of size, shape, or composition, usually assessed byanthropometry(seeAnthropometry). Indeed, the termgrowthis often used as a shorthand for child anthropometry. Development reflects maturation as measured by ordinal markers of function; some markers are inherently discontinuous, while others have an underlying continuum. Menarche, the onset of menstruation, is a marker of development, while height gain is a measure of growth.

The statistical issues that arise in growth and development fall broadly into two categories: methods for cross‐sectional data, notably the construction of growth references, and methods for longitudinal data, particularly growth curve analysis.
Tolerance Interval
Authors: Vangel Mark G.
Published: September 2015

Tolerance intervals cover at least a specified proportion of a population, either on average or else with a stated level of confidence. The theory is described in relation to simple random samples and regression models. Topics discussed include mixed‐model tolerance intervals, random effects tolerance intervals, simultaneous tolerance intervals, and applications to calibration. Methods are illustrated by an example on serum glucose measurements.
Tolerance Region: Definition
Authors: Vangel Mark G.
Published: September 2015

In a sample from a multivariate distribution, a tolerance region is a region for which there is a specified high probability (theconfidence) that at least a specified proportion of the distribution (thecoverage) is included. It is thus a generalization of the univariate tolerance interval. The construction using statistically equivalent blocks is described briefly.
Data Monitoring Committees Including Operational Issues
Authors: Ellenberg Susan
Published: September 2015

Data Monitoring Committees, also known asData and Safety Monitoring Boards, are often established as a component of clinical trial oversight to review interim data of the ongoing trial so that safety concerns or problematic operational issues can be identified rapidly and corrective measures can be undertaken. Such committees may be independent of the trial sponsor and investigator to ensure recommendations are as objective as possible and unaffected by conflicts of interest. Federal funding and regulatory agencies have issued policy documents concerning the establishment and operation of Data Monitoring Committees, but substantial variation exists in committee processes.
deFinetti's Representation Theorem
Authors: Regazzini Eugenio
Published: September 2015

This entry deals with the de Finetti representation theorem of the law of a sequence of exchangeable random elements. In addition to the formulation of the theorem and a few comments on its proof, its impact on the foundations of statistics (principle of induction) is analyzed.
Just the Two of Us…We Can Make It If We Try: The Relationship Between Social Justice and Doctoral Studies
Authors: Ramdeholl Dianne
Published: September 2015

This chapter explores the journey of a former adult literacy worker into the academy. She reflects on her commitment to social justice education and implications for doctoral studies.
Africentrism—Standing on Its Own Cultural Ground
Authors: Tolliver Derise E.
Published: September 2015

Africentrism is a conceptual framework that is rooted in the epistemology, cosmology, and axiology of the indigenous African worldview. Understanding the basic principles and values of this transformative paradigm can inform doctoral programs’ efforts to enhance inclusion by undoing practices of marginalization and hegemony.
Into the Future, One Second at a Time
Authors: Heaney Tom , Ramdeholl Dianne
Published: September 2015

In this chapter, the editors review the contributions of each chapter to a vision for doctoral education viewed through the lens of the best practices of adult education.
Crashing Memory 2.0: False Memories in Adults for an Upsetting Childhood Event
Authors: Patihis Lawrence , Loftus Elizabeth F.
Published: September 2015

Previous crashing memory studies have shown that adults can be led to believe they witnessed video footage of news events for which no video footage actually exists. The current study is the first to investigate adults' tendency to report memories of viewing footage that took place when they were children: the plane crash in Pennsylvania on 11 September 2001. We found that in a computer questionnaire, 33% indicated a false memory with at least one false detail. In a more detailed face‐to‐face interview, only 13% of the group described a detailed false memory. Familiarity with the news story, fantasy proneness, alcohol use, and frequency of negative emotions after 9/11 were all associated with a Persistent False Memory. Participants who had received prior suggestion were more likely to later report false memories in the subsequent interview. We discuss our novel results and the importance of the paradigm.Copyright © 2015 John Wiley & Sons, Ltd.
Reducing the Misinformation Effect Through Initial Testing: Take Two Tests and Recall Me in the Morning?
Authors: Huff Mark J. , Weinsheimer Camille C. , Bodner Glen E.
Published: September 2015

Initial retrieval of an event can reduce people's susceptibility to misinformation. We explored whether protective effects of initial testing could be obtained on final free recall and source‐monitoring tests. After studying six household scenes (e.g., a bathroom), participants attempted to recall items from the scenes zero, one, or two times. Immediately or after a 48‐hour delay, non‐presented items (e.g., soap and toothbrush) were exposed zero, one, or four times through a social contagion manipulation in which participants reviewed sets of recall tests ostensibly provided by other participants. A protective effect of testing emerged on a final free recall test following the delay and on a final source‐memory test regardless of delay. Taking two initial tests did not increase these protective effects. Determining whether initial testing will have protective (versus harmful) effects on memory has important practical implications for interviewing eyewitnesses. © 2015 The Authors. Applied Cognitive Psychology published by John Wiley & Sons, Ltd.
Microstructural and Mechanical Properties of Al‐Based Composites Reinforced with In‐Situ and Ex‐Situ Al2O3 Nanoparticles
Authors: Casati Riccardo , Fabrizi Alberto , Timelli Giulio , Tuissi Ausonio , Vedani Maurizio
Published: September 2015

A powder metallurgy route based on high‐energy ball milling and powder consolidation by ECAP is used to produce Al‐matrix composites reinforced with Al2O3 nanoparticles. The reinforcement is produced in‐situ during the milling process and added ex‐situ. Ball milling led to the fragmentation of the oxide layer that covers the Al particles and to the formation of very thin Al2O3 dispersoids. Moreover, it was able to break the Al2O3 particle clusters added ex‐situ and to embed the oxide in the ductile Al matrix. After powder consolidation by ECAP, the nanocomposites showed an ultra‐fine grained and fully dense matrix characterized by uniformly dispersed nanoparticles.
Effect of Shape, Size, and Aspect Ratio on Nanoparticle Penetration and Distribution inside Solid Tissues Using 3D Spheroid Models
Authors: Agarwal Rachit , Jurney Patrick , Raythatha Mansi , Singh Vikramjit , Sreenivasan Sidlgata. V. , Shi Li , Roy Krishnendu
Published: September 2015

Efficient penetration and uniform distribution of nanoparticles (NPs) inside solid tissues and tumors is paramount to their therapeutic and diagnostic success. While many studies have reported the effect of NP size and charge on intratissue distribution, role of shape, and aspect ratio on NP transport inside solid tissues remain unclear. Here experimental and theoretical studies are reported on how nanoscale geometry of Jet and Flash Imprint Lithography‐fabricated, polyethylene‐glycol‐based anionic nanohydrogels affect their penetration and distribution inside 3D spheroids, a model representing the intervascular region of solid, tumor‐like tissues. Unexpectedly, low aspect ratio cylindrical NPs (H/D ≈0.3; disk‐like particles, 100 nm height, and 325 nm diameter) show maximal intratissue delivery (>50% increase in total cargo delivered) and more uniform penetration compared to nanorods or smaller NPs of the same shape. This is in contrast to spherical NPs where smaller NP size resulted in deeper, more uniform penetration. Our results provide fundamental new knowledge on NP transport inside solid tissues and further establish shape and aspect ratio as important design parameters in developing more efficient, better penetrating, nanocarriers for drug, or contrast‐agent delivery.
Facile Fabrication of Egg White Macroporous Sponges for Tissue Regeneration
Authors: Jalili‐Firoozinezhad Sasan , Rajabi‐Zeleti Sareh , Mohammadi Parvaneh , Gaudiello Emanuele , Bonakdar Shahin , Solati‐Hashjin Mehran , Marsano Anna , Aghdami Nasser , Scherberich Arnaud , Baharvand Hossein , Martin Ivan
Published: September 2015

The availability of 3D sponges combining proper biochemical, biophysical, and biomechanical properties with enhanced capacity of in vivo engraftment and vascularization is crucial in regenerative medicine. A simple process is developed to generate macroporous scaffolds with a well‐defined architecture of interconnected pores from chicken egg white (EW), a material with protein‐ and growth factor‐binding features which has not yet been employed in regenerative medicine. The physicomechanical properties and degradation rates of the scaffold are finely tuned by using varying concentrations of the cross‐linker, 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide hydrochloride, without alteration of the biochemical traits. In vitro, EW scaffolds supported active metabolism, proliferation, and migration of human dermal fibroblasts, thereby generating uniform cellular constructs. In vivo, subcutaneous implantation in mice reveals negligible immune reaction and efficient cell and tissue ingrowth. Angiogenesis into EW scaffolds is enhanced as compared to standard collagen type I sponges used as reference material, likely due to significantly higher adsorption of the proangiogenic factor vascular endothelial growth factor. In summary, a material is presented derived by facile processing of a highly abundant natural product. Due to the efficient subcutaneous engraftment capacity, the sponges can find utilization for soft tissue regeneration.
Bleeding spectrum in children with moderate or severe von Willebrand disease: Relevance of pediatric‐specific bleeding
Authors: Sanders Yvonne V. , Fijnvandraat Karin , Boender Johan , Mauser‐Bunschoten Evelien P. , van der Bom Johanna G. , de Meris Joke , Smiers Frans J. , Granzen Bernd , Brons Paul , Tamminga Rienk Y.J. , Cnossen Marjon H. , Leebeek Frank W.G. ,   the WiN Study Group
Published: September 2015

The bleeding phenotype of children with von Willebrand disease (VWD) needs to be characterized in detail to facilitate diagnosis during childhood and aid in the planning and assessment of treatment strategies. The objective was to evaluate the occurrence, type, and severity of bleeding in a large cohort of children with moderate and severe VWD. We included 113 children (aged 0–16 years) with Type 1 (n = 60), 2 (n = 44), and 3 (n = 9) VWD with von Willebrand factor (VWF) antigen and/or VWF ristocetin cofactor levels ≤ 30 U/dL from a nation‐wide cross‐sectional study (“Willebrand in the Netherlands” study). Bleeding severity and frequency were determined using the International Society on Thrombosis and Hemostasis‐Bleeding Assessment Tool (ISTH‐BAT) with supplementary pediatric‐specific bleeding symptoms (umbilical stump bleeding, cephalohematoma, cheek hematoma, conjunctival bleeding, postcircumcision and postvenipuncture bleeding). We found that all 26 postmenarche girls experienced menorrhagia. Other common bleedings were cutaneous (81%), oropharyngeal (64%), prolonged bleeding from minor wounds (58%), and epistaxis (56%). Pediatric‐specific bleeding symptoms were present in 44% of patients. ISTH‐BAT bleeding score was higher in index cases than in affected family members (median, 12.0 vs. 6.5, P < 0.001), higher in Type 3 VWD than in Type 2 or 1 (17.0 vs. 10.5 or 6.5, P < 0.001) and higher in children with severe (<10 U/dL) than moderate VWD (10–30 U/dL) (11.0 vs. 7.0, P < 0.001). Frequency of any bleeding, epistaxis, and oral cavity was higher in types 2 and 3 than in Type 1 VWD and was associated with VWF levels. We conclude that pediatric‐specific bleeding symptoms occurred in a large proportion of children with moderate or severe VWD and should be included when evaluating children for VWD. Am. J. Hematol. 90:1142–1148, 2015. © 2015 Wiley Periodicals, Inc.
Minor anomalies in stillborn and second trimester miscarried fetuses
Authors: McPherson Elizabeth , Cold Christopher
Published: September 2015

In 1964, the landmark paper of Marden, Smith, and McDonald established that multiple minor anomalies in newborn infants are associated with an increased risk for major malformations. There were until now no comparable studies in stillbirths. The Wisconsin Stillbirth Service Program (WiSSP) has data regarding nearly 3,000 stillbirths and second trimester losses that have been analyzed for major anomalies and cause of death. One dysmorphologist retrospectively reviewed all 2,397 with usable photographs. Minor anomalies were identified in 1,413 (59%) with 575 of these (41%) having at least one major anomaly. Probability of a major anomaly increased from 7% with no minor anomalies to 15%, 36%, 67%, and 89% with 1, 2, 3, and >33 minor anomalies, respectively. Frequency of minor anomalies was less with lower resolution photographs, but did not show significant differences with maceration or gestational age. The most frequent minor anomalies were infraorbital creases/folds, lowset/posteriorly angulated ears, nuchal edema, flat face, equinovarus foot, camptodactyly, upslanted palpebral fissures, ear antihelix abnormalities (combined), micrognathia/retrognathia, and single transverse palmar crease. Except for infraorbital creases/folds each of these minor anomalies was strongly correlated with major anomalies (P < 0.0001). Infraorbital folds were the only anomaly which increased with placental cause of death, and reanalysis with placental causes excluded showed the expected relationship to major anomalies, suggesting that infraorbital folds may be markers for oligohydramnios due to various causes including placental hypoperfusion. Minor anomalies correlate with presence of major anomalies in stillborn fetuses, regardless of gestational age and maceration, and can provide information to guide decisions regarding laboratory testing and other evaluations. © 2015 Wiley Periodicals, Inc.
Compound heterozygous variants in the LARP7 gene as a cause of Alazami syndrome in a Caucasian female with significant failure to thrive, short stature, and developmental disability
Authors: Ling Tina T. , Sorrentino Susanna
Published: September 2015

Alazami syndrome is an autosomal recessive disease characterized by primordial dwarfism, distinct dysmorphic features, and severe intellectual disability. Since it was first identified in a large consanguineous Arabic family in 2012, additional cases have not been published in the literature. We present a 2‐year‐old Northern European/Caucasian female with short stature, failure to thrive, and developmental delay. Whole exome sequencing (WES) identified two novel pathogenic variants in LARP7 (c.213_214dup and c.651_655del), indicating a diagnosis of Alazami syndrome. The case report describes a novel genotypic and phenotypic presentation of Alazami syndrome, contributing to the current knowledge of the condition as well as the expansion of differential diagnoses for growth restriction and intellectual disability. © 2015 Wiley Periodicals, Inc.
Laboratory simulations of mate‐guarding as a component of the pair‐bond in male titi monkeys, Callicebus cupreus
Authors: Fisher‐Phelps Marina L. , Mendoza Sally P. , Serna Samantha , Griffin Luana L. , Schaefer Thomas J. , Jarcho Michael R. , Ragen Benjamin J. , Goetze Leana R. , Bales Karen L.
Published: September 2015

Mate‐guarding and territorial aggression (both intra‐ and inter‐sexual) are behavioral components of social monogamy seen in male coppery titi monkeys (Callicebus cupreus) both in the field and in the laboratory. Methodology for studying these behaviors in captivity facilitates the translation of questions between field and laboratory. In this study, we tested whether exposure to a mirror would stimulate mate‐guarding behavior in male titi monkeys, and whether this exposure was accompanied by hormonal changes. Eight males were exposed to a mirror condition (treatment) or the back of the mirror (control) for five sessions, and behavioral responses were filmed. Blood samples were taken to measure levels of cortisol, oxytocin, and vasopressin. Lipsmacks (P < 0.0001), arching (P < 0.0001), tail‐lashing (P = 0.009), restraining (P = 0.015), and approaches to the female (P = 0.0002) were all higher during the mirror condition, while tail‐twining tended to decline during the mirror condition (P = 0.076). Hormones did not vary by experimental treatment, but were correlated with certain behaviors during the presentation of the mirror. While social behaviors changed with mirror exposure, self‐directed and mirror‐guided behaviors did not, indicating a lack of self‐recognition. Use of a mirror was a safe and effective means of investigating mate‐guarding behavior in response to a simulated intrusion, with the added benefit of not needing another animal to serve as an intruder; and thus may be of use in providing a laboratory model for natural behavior. Especially, as it eliminates the need for a stimulus animal, it would also be of possible use in investigating responses to a simulated intruder in wild populations of titis and other pithecines. Am. J. Primatol. 78:573–582, 2016. © 2015 Wiley Periodicals, Inc.
Isotactic rac‐Lactide Polymerization with Copper Complexes: The Influence of Complex Nuclearity
Authors: Fortun Solène , Daneshmand Pargol , Schaper Frank
Published: September 2015

Diiminopyrrolide copper alkoxide complexes, LCuOR (OR1=N,N‐dimethylamino ethoxide, OR2=2‐pyridyl methoxide), are active for the polymerization of rac‐lactide at ambient temperature in benzene to yield polymers with Mw/Mn=1.0–1.2. X‐ray diffraction studies showed bridged dinuclear complexes in the solid state for both complexes. While LCuOR1 provided only atactic polylactide, LCuOR2 produced partially isotactic polylactide (Pm=0.7). The difference in stereocontrol is attributed to a dinuclear active species for LCuOR2 in contrast to a mononuclear species for LCuOR1.
X‐ray Crystallography in Open‐Framework Materials
Authors: Bloch Witold M. , Champness Neil R. , Doonan Christian J.
Published: September 2015

Open‐framework materials, such as metal–organic frameworks (MOFs) and coordination polymers have been widely investigated for their gas adsorption and separation properties. However, recent studies have demonstrated that their highly crystalline structures can be used to periodically organize guest molecules and non‐structural metal compounds either within their pore voids or by anchoring to their framework architecture. Accordingly, the open framework can act as a matrix for isolating and elucidating the structures of these moieties by X‐ray diffraction. This concept has broad scope for development as an analytical tool where obtaining single crystals of a target molecule presents a significant challenge and it additionally offers potential for obtaining insights into chemically reactive species that can be stabilized within the pore network. However, the technique does have limitations and as yet a general experimental method has not been realized. Herein we focus on recent examples in which framework materials have been utilized as a scaffold for ordering molecules for analysis by diffraction methods and canvass areas for future exploration.
Structural, Biochemical, and Computational Studies Reveal the Mechanism of Selective Aldehyde Dehydrogenase 1A1 Inhibition by Cytotoxic Duocarmycin Analogues
Authors: Koch Maximilian F. , Harteis Sabrina , Blank Iris D. , Pestel Galina , Tietze Lutz F. , Ochsenfeld Christian , Schneider Sabine , Sieber Stephan A.
Published: September 2015

Analogues of the natural product duocarmycin bearing an indole moiety were shown to bind aldehyde dehydrogenase 1A1 (ALDH1A1) in addition to DNA, while derivatives without the indole solely addressed the ALDH1A1 protein. The molecular mechanism of selective ALDH1A1 inhibition by duocarmycin analogues was unraveled through cocrystallization, mutational studies, and molecular dynamics simulations. The structure of the complex shows the compound embedded in a hydrophobic pocket, where it is stabilized by several crucial π‐stacking and van der Waals interactions. This binding mode positions the cyclopropyl electrophile for nucleophilic attack by the noncatalytic residue Cys302, thereby resulting in covalent attachment, steric occlusion of the active site, and inhibition of catalysis. The selectivity of duocarmycin analogues for ALDH1A1 is unique, since only minor alterations in the sequence of closely related protein isoforms restrict compound accessibility.
Chemically Locked Bicelles with High Thermal and Kinetic Stability
Authors: Matsui Ryoichi , Ohtani Masataka , Yamada Kuniyo , Hikima Takaaki , Takata Masaki , Nakamura Takashi , Koshino Hiroyuki , Ishida Yasuhiro , Aida Takuzo
Published: September 2015

In situ polymerization of a bicellar mixture composed of a phospholipid and polymerizable surfactants afforded unprecedented stable bicelles. The polymerized composite showed an aligned phase over a wide thermal range (25 to >90 °C) with excellent 2H quadrupole splitting of the solvent signal, thus implying versatility as an alignment medium for NMR studies. Crosslinking of the surfactants also brought favorable effects on the kinetic stability and alignment morphology of the bicelles. This system could thus offer a new class of scaffolds for biomembrane models.
Room‐temperature Suzuki–Miyauracross‐coupling reaction with α‐diimine Pd(II) catalysts
Authors: Wang Fuzhou , Tanaka Ryo , Cai Zhengguo , Nakayama Yuushou , Shiono Takeshi
Published: September 2015

An α‐diimine Pd(II) complex containing chiral sec‐phenethyl groups, {bis[N,N′‐(4‐methyl‐2‐sec‐phenethylphenyl)imino]‐2,3‐butadiene}dichloropalladium (rac‐C1), was synthesized and characterized. rac‐C1 was applied as an efficient catalyst for the Suzuki–Miyaura cross‐coupling reaction between various aniline halides and arylboronic acid in PEG‐400–H2O at room temperature. Among a series of aniline halides, rac‐C1 did not catalyze the cross‐coupling of aniline chlorides and fluorides but efficiently catalyzed the cross‐coupling of aniline bromides and iodides with phenylboronic acid. The catalytic activity reduced slightly with increasing steric hindrance of the aniline bromides. The complexes {bis[N,N′‐(4‐fluoro‐2,6‐diphenylphenyl)imino]‐2,3‐butadiene}dichloropalladium and {bis[N,N′‐(4‐fluoro‐2,6‐diphenylphenyl)imino]acenaphthene}dichloropalladium were also found to be efficient catalysts for the reaction. Copyright © 2015 John Wiley & Sons, Ltd.
ForceSpinning of polyacrylonitrile for mass production of lithium‐ion battery separators
Authors: Agubra Victor A. , De la Garza David , Gallegos Luis , Alcoutlabi Mataz
Published: September 2015

We present results on the Forcespinning® (FS) of Polyacrylonitrile (PAN) for mass production of polymer nanofiber membranes as separators for Lithium‐ion batteries (LIBs). Our results presented here show that uniform, highly fibrous mats from PAN produced using Forcespinning®, exhibit improved electrochemical properties such as electrolyte uptake, low interfacial resistance, high oxidation limit, high ionic conductivity, and good cycling performance when used in lithium ion batteries compared to commercial PP separator materials. This article introduces ForceSpinning®, a cost effective technique capable of mass producing high quality fibrous mats, which is completely different technology than the commonly used in‐house centrifugal method. This Forcespinning® technology is thus the beginning of the nano/micro fiber revolution in large scale production for battery separator application. This is the first time to report results on the cycle performance of LIB‐based polymer nanofiber separators made by Forcespinning® technology. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 132, 42847.
Selective solid‐phase extraction of metal for water decontamination
Authors: Mane Sachin , Ponrathnam Surendra , Chavan Nayaku
Published: September 2015

Metal‐contaminated industrial effluent is a major concern for human health. Therefore, the removal of metal is of primary importance. In this study, metals were selectively extracted from water. Selective metal recovery was studied with a crown‐ether‐based polymer, wherein the selectivity was observed for strontium over lead. Parameters influencing the metal recovery, such as the contact time, adsorbent dosage, and metal‐ion concentration, were evaluated. Interestingly, the adsorption rate of strontium was exponentially increased for the initial 4 h, and lead was adsorbed exponentially after 6 h. Notably, 98% strontium adsorption and 64% lead adsorption were obtained in 24 h. The Langmuir adsorption isotherm was in good agreement and demonstrated that the reactive sites of the adsorbent were homogeneous with monolayer metal adsorption with an adsorbent. The Freundlich adsorption isotherm was not obeyed by both metals. The pseudo‐first‐order and pseudo‐second‐order kinetics indicated that strontium was adsorbed by chemisorption and lead was adsorbed by physisorption. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 132, 42849.
Electrospun biodegradable nanofibers scaffolds for bone tissue engineering
Authors: Khajavi Ramin , Abbasipour Mina , Bahador Abbas
Published: September 2015

Many polymeric materials have been developed and introduced for bone regeneration. Especially, their nanofibrous forms are mostly applied for artificial extracellular matrices. Polymeric materials in their nanofibrous form show some potent properties such as high surface‐to‐volume ratio, tunable porosity, and ease of surface functionalization. Benefiting from the properties of their main polymer and additives, they can provide new opportunities for cell seeding, proliferation, and new 3D‐tissue formation. This article focuses on most cited polymeric nanofibrous scaffolds fabricated by electrospinning and recent achievements. They were divided into two main categories: natural (collagen, silk, keratin, gelatin, chitosan, and alginate) and synthetic (e.g., polycaprolactone, polylactic acid, and polyglycolic acid) polymers. The role of several additives like hydroxyapatite, bone morphogenetic proteins (BMPs), tricalcium phosphate, and collagen type I in improving the adhesion, differentiation, and tissue formation of stem cells were discussed. Finally, the osteogenic capacity and ability of nanofibrous scaffolds to support the growth of clinically relevant bone tissue were briefly studied. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2016,133, 42883.
Gold‐Catalyzed Intramolecular Tandem Cyclization of Indole‐Ynamides: Diastereoselective Synthesis of Spirocyclic Pyrrolidinoindolines
Authors: Zheng Nan , Chang Yuan‐Yuan , Zhang Li‐Jie , Gong Jian‐Xian , Yang Zhen
Published: September 2015

A gold‐catalyzed intramolecular tandem cyclization of indole‐ynamide affords tetracyclic spirocyclic pyrrolidinoindoline bearing an all‐carbon quaternary stereocentre in a single step; however, when the reaction was carried out in the presence of BF3⋅Et2O, the corresponding tricyclic spirocyclic pyrrolidinoindoline‐based enones are produced through a key 1,5‐hydride shift. The developed chemistry provides a diastereoselective and straightforward entry to structurally diverse polycylic pyrrolidinoindolines from indole‐ynamides in one‐pot reactions under mild conditions.
HepG2 Cell Resistance against Camptothecin from a Lysosomal Drug Delivery
Authors: Lee Hoyeon , Uhm Soojin , Shin Jung‐Won , Jeon Hyun Mi , Dongbang Sun , Jung Hyo Sung , Na Yun‐Cheol , Kang Chulhun , Kim Jong Seung
Published: September 2015

A galactose‐appended drug delivery system released camptothecin (CPT) to lysosomes of HepG2 hepatoma cells, resulting in the cell resistance to the anticancer drug. We found that the resistance to CPT is caused by alteration of the drug release from the prodrug in lysosomes, emphasizing that the final delivery locations may critically influence drug efficacy.
Squeeze flow rheometry as a novel tool for the characterization of highly concentrated protein solutions
Authors: Schermeyer Marie‐Therese , Sigloch Heike , Bauer Katharina C. , Oelschlaeger Claude , Hubbuch Jürgen
Published: September 2015

This study aims at defining rheological parameters for the characterization of highly concentrated protein solutions. As a basis for comparing rheological behavior with protein solution characteristics the protein phase behavior of Lysozyme from chicken egg white with concentrations up to 225 mg/mL, changing pH values and additive concentrations was studied in a microbatch scale format. The prepared phase diagrams, scored after 40 days () give insights into the kind and kinetics of the phase transitions that occur. Oscillatory frequency sweep measurements of samples with exactly the same conditions were conducted immediately after preparation (). The protein solutions behave viscoelastic and show a characteristic curve shape of the storage modulus (G′) and the loss modulus (G″). The graphs provide information about the cross‐linking degree of the respective sample. The measured rheological parameters were sensitive concerning solution composition, protein concentration and solution inner structure. The rheological moduli G′ and G″ and especially the ratio of these parameters over a frequency range from 100 to 40000 rad/sec give information about the aggregation tendency of the protein under tested conditions. We succeeded to correlate protein phase behavior with the defined rheological key parameter . This point represents the frequency value of the intersection point from G′ and G″. In our study Lysozyme expressed a threshold value of 20000 rad/sec as a lower limit for stable protein solutions. The predictability of lysozyme aggregation tendency and crystallization by means of squeeze flow rheometry is shown. Biotechnol. Bioeng. 2016;113: 576–587. © 2015 Wiley Periodicals, Inc.
Systematic review of sarcopenia in patients operated on for gastrointestinal and hepatopancreatobiliary malignancies
Authors: Levolger S , van Vugt J L A , de Bruin R W F , IJzermans J N M
Published: September 2015

Background

Preoperative risk assessment in cancer surgery is of importance to improve treatment and outcome. The aim of this study was to assess the impact of CT-assessed sarcopenia on short- and long-term outcomes in patients undergoing surgical resection of gastrointestinal and hepatopancreatobiliary malignancies.

Methods

A systematic search of Embase, PubMed and Web of Science was performed to identify relevant studies published before 30 September 2014. PRISMA guidelines for systematic reviews were followed. Screening for inclusion, checking the validity of included studies and data extraction were carried out independently by two investigators.

Results

After screening 692 records, 13 observational studies with a total of 2884 patients were included in the analysis. There was wide variation in the reported prevalence of sarcopenia (17·0–79 per cent). Sarcopenia was independently associated with reduced overall survival in seven of ten studies, irrespective of tumour site. Hazard ratios (HRs) of up to 3·19 (hepatic cancer), 1·63 (pancreatic cancer), 1·85 (colorectal cancer) and 2·69 (colorectal liver metastases, CLM) were reported. For oesophageal cancer, the HR was 0·31 for increasing muscle mass. In patients with colorectal cancer and CLM, sarcopenia was independently associated with postoperative mortality (colorectal cancer: odds ratio (OR) 43·3), complications (colorectal cancer: OR 0·96 for increasing muscle mass; CLM: OR 2·22) and severe complications (CLM: OR 3·12).

Conclusion

Sarcopenia identified before surgery by single-slice CT is associated with impaired overall survival in gastrointestinal and hepatopancreatobiliary malignancies, and increased postoperative morbidity in patients with colorectal cancer with or without hepatic metastases.
Formaldehyde exposure and its effects during pregnancy: Recommendations for laboratory attendance based on available data
Authors: Haffner Matthew J. , Oakes Peter , Demerdash Amin , Yammine Kaissar Cesar , Watanabe Koichi , Loukas Marios , Tubbs R. Shane
Published: September 2015

Formalin is commonly used in fixation of cadaveric specimens. Exposure to formaldehyde, a component of formalin and a known carcinogen, during gross anatomy laboratory dissection is a continuing concern for pregnant students and instructors. Since there is little literature on this specific topic, the current review was compiled in the hope of offering recommendations to pregnant students and instructors who are engaged in human anatomical dissection where formalin is used. Relevant articles were obtained through searches of PubMed and Google Scholar for the terms “formaldehyde,” “pregnant,” “formalin,” and “exposure.” A literature search was conducted for chemical information and articles about exposure as issued by government regulatory agencies and chemical companies that produce formaldehyde. This led to the compilation of 29 articles each of which included references to previous, relevant, human research. The reviewed literature contains data strongly suggesting that pregnancy can be affected by formaldehyde exposure. Therefore, on the basis our analysis, female students who might be pregnant should avoid formaldehyde exposure, including that in a gross anatomy laboratory. Instructors should find other means of ensuring anatomical competence for these students. Clin. Anat. 28:972–979, 2015. © 2015 Wiley Periodicals, Inc.
Avoid “other duties as assigned”: The importance of higher education emergency managers
Authors: Zacarese Lawrence M.
Published: September 2015

I recently returned from several weeks of traveling and speaking at some national and regional conferences. The focus of my lectures was organizational resiliency and continuity of operations in the context of a major regional hurricane, the impacts on a large research university, and the crucial role that my university (and others) played in the response and recovery. Specifically, I discussed the importance of leveraging technology to achieve resiliency, but the main takeaway from my talks centered on the importance of a “continuity culture” within institutions of higher education — namely, establishing this understanding among all levels of administration. In my humble but experienced opinion, this mindset is sorely lacking among the vast majority of higher education institutions. The content of my lectures did not change, although the venue and demographics of the attendees did. The juxtaposition was interesting to me, although not completely surprising.
Provide training to ensure safety on multiple campuses
Authors: Hope Joan
Published: September 2015

Overseeing the Campus Safety Program at the University of Phoenix's more than 90 campuses and learning centers makes for a challenging job. Lara Fox, an ethics and compliance program manager, provides training for the campus security authorities on each campus, manages the campus crime statistics for all the campuses, and maintains the university's campus safety policies.
Genome‐wide screen of promoter methylation analysis of ES cells and ES derived epidermal‐like cells
Authors: Zhang Ren‐li , Meng Jin‐xiu , Liu Cai‐xia , Zhang Li‐li , Han Dong , Cai Jia‐jie , Wen An‐min
Published: September 2015

Embryonic stem cells (ESCs) are a population of pluripotent cells which can differentiate into different cell types. However, there are few reports with regard to differentiate ESCs into epidermal cells in vitro. In this study, we aimed to investigate differentially methylated promoters involved in process of differentiation from ESCs into epidermal‐like cells (ELCs) induced by human amnion. We successfully induced ESCs into ELCs, which expressed the surface markers of CK19, CK15 and β1‐integrin. With MeDIP‐chip arrays, we identified 3435 gene promoters to be differentially methylated, involving 894 HCP (high CpG‐containing promoter), 974 ICP (intermediate CpG‐containing promoter) and 1567 LCP (low CpG‐containing promoter) among all the 17 500 DNA methylation regions of gene promoters in both ESCs and ELCs. Gene oncology and pathway analysis demonstrated that these genes were involved in all the three categories of GO enrichment analysis, including biological process, molecular function and cellular component. All these data suggested that embryonic stem cells can differentiate into epidermal‐like cells and promoter methylation is of great importance in this process. Copyright © 2015 John Wiley & Sons, Ltd.
Ovarian ectopic pregnancy in adolescence
Authors: Andrade Ana Gonçalves , Rocha Sara , Marques Catarina O. , Simões Mafalda , Martins Isabel , Biscaia Isabel , F. Barros Carlos
Published: September 2015

Key Clinical Message

Ovarian pregnancy is one of the rarest types of extrauterine pregnancy. Its preoperative diagnosis remains a challenge since it presents quite similarly to tubal pregnancy and complicated ovarian cysts. Although in most cases, histology is necessary to confirm the diagnosis, we present an ovarian pregnancy in a teenager, correctly diagnosed during ultrasound examination.
Long‐term persistent fetomaternal hemorrhage
Authors: Umazume Takeshi , Morikawa Mamoru , Yamada Takahiro , Cho Kazutoshi , Masauzi Nobuo , Minakami Hisanori
Published: September 2015

Key Clinical Message

It is not clear that how long the affected fetuses can tolerate fetomaternal hemorrhage (FMH). Incidental serial measurements of the fetal peak systolic velocity of the middle cerebral artery and the retrospective analysis of stocked blood available incidentally indicated that our patient had suffered from FMH for at least 2 weeks prior to delivery.