bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic process conditions in bioprocess development
Authors: Spadiut Oliver , Rittmann Simon , Dietzsch Christian , Herwig Christoph
Published: January 2013

In this review, we summarise recent studies that purposefully employed dynamic conditions, such as shifts, pulses, ramps and oscillations, for fast physiological strain characterisation and bioprocess development. We show the broad applicability of dynamic conditions and the various objectives that can thereby be investigated in a short time. Dynamic processes reveal information about the analysed system faster than traditional strategies, like continuous cultivations, as process parameters can directly be linked to platform and product parameters. Furthermore, we demonstrate that dynamic operations can result in increased productivity and high product quality, making this strategy a valuable tool for bioprocess development. With this review, we would like to encourage bioprocess engineers to an increased use of dynamic conditions in bioprocess development.
Data assimilation for large‐scale spatio‐temporal systems using a location particle smoother
Authors: Briggs Jonathan , Dowd Michael , Meyer Renate
Published: January 2013

Data assimilation estimates the time evolution of the probability density function (PDF) of state vectors characterising high‐dimensional nonlinear spatiotemporal dynamic systems, making use of available observations. The current best‐practice statistical data assimilation technique – the ensemble Kalman filter – relies on restrictive normality assumptions. The particle filter provides a methodology for estimating these PDFs without requiring these restrictive distributional assumptions using samples drawn from the conditional state PDF given available observations. Unfortunately, particle filter weight collapse is severe when the state and/or observation vectors are high dimensional, making them impractical for systems with a spatial component. We offer a solution to this problem by drawing the required sample from the conditional PDF at each time step using a particle smoother across the spatial locations. A further innovation is the use of meta‐elliptical copulas to provide a general framework for defining the prediction PDFs – one flexible enough to accurately describe the numerical model errors and fast enough to sample to be applicable in practice. The proposed methods perform well compared with other candidate approaches in a 1000 dimensional spatiotemporal simulation study and a real 1750 dimensional marine ecosystem application based on partial differential equations and ocean monitoring data. Copyright © 2013 John Wiley & Sons, Ltd.
LTE networking: extending the reach for sensors in mHealth applications
Authors: Adibi Sasan , Mobasher Amin , Tofigh Tom
Published: January 2013

Sensor and electronic‐health networks are widely utilized at home and in industry/research applications. In a local sense, a sensor‐to‐sensor network can have a range of a few meters to a couple of hundred meters (ZigBee Pro can extend this range up to 2000 m). With the deployment of mobile technology in the healthcare space (mobile‐Health ‘m‐Health’) and using cellular coverage, the range can virtually be unbounded. However, supporting bounded delay (end‐to‐end delay), class of service, and quality of service for critical sensor‐mHealth applications may become challenging. This challenge can be alarmingly extended when thousands of users run their sensor‐mHealth applications simultaneously and depend on limited coverage of the cell tower to transmit their health‐related data across. In this paper we will discuss how the 3rd Generation Partnership Project–Long Term Evolution networks can address such aggregation issues, and discuss the challenges and provide recommendations.Copyright © 2013 John Wiley & Sons, Ltd.
A robust non‐data‐aided SNR estimation method for OFDM systems
Authors: Sheng Bin
Published: January 2013

The information of signal‐to‐noise ratio (SNR) plays an important role in orthogonal frequency division multiplexing (OFDM) systems. Some applications, such as cognitive radio, need non‐data‐aided (NDA) estimation of SNR. In this paper, we propose a robust NDA SNR estimation method, which is developed on the basis of the cyclic prefix of OFDM symbol. The proposed method is immune to the inter‐symbol interference caused by multipath channel and can thus obtain an unbiased estimate of the signal power even in the low‐SNR regime. Copyright © 2013 John Wiley & Sons, Ltd.
Importance of Different Types of Prior Knowledge in Selecting Genome‐Wide Findings for Follow‐Up
Authors: Minelli Cosetta , De Grandi Alessandro , Weichenberger Christian X. , Gögele Martin , Modenese Mirko , Attia John , Barrett Jennifer H. , Boehnke Michael , Borsani Giuseppe , Casari Giorgio , Fox Caroline S. , Freina Thomas , Hicks Andrew A. , Marroni Fabio , Parmigiani Giovanni , Pastore Andrea , Pattaro Cristian , Pfeufer Arne , Ruggeri Fabrizio , Schwienbacher Christine , Taliun Daniel , Pramstaller Peter P. , Domingues Francisco S. , Thompson John R.
Published: January 2013

Biological plausibility and other prior information could help select genome‐wide association (GWA) findings for further follow‐up, but there is no consensus on which types of knowledge should be considered or how to weight them. We used experts’ opinions and empirical evidence to estimate the relative importance of 15 types of information at the single‐nucleotide polymorphism (SNP) and gene levels. Opinions were elicited from 10 experts using a two‐round Delphi survey. Empirical evidence was obtained by comparing the frequency of each type of characteristic in SNPs established as being associated with seven disease traits through GWA meta‐analysis and independent replication, with the corresponding frequency in a randomly selected set of SNPs. SNP and gene characteristics were retrieved using a specially developed bioinformatics tool. Both the expert and the empirical evidence rated previous association in a meta‐analysis or more than one study as conferring the highest relative probability of true association, whereas previous association in a single study ranked much lower. High relative probabilities were also observed for location in a functional protein domain, although location in a region evolutionarily conserved in vertebrates was ranked high by the data but not by the experts. Our empirical evidence did not support the importance attributed by the experts to whether the gene encodes a protein in a pathway or shows interactions relevant to the trait. Our findings provide insight into the selection and weighting of different types of knowledge in SNP or gene prioritization, and point to areas requiring further research.
Preserving ecosystem services in urban regions: Challenges for planning and best practice examples from Switzerland
Authors: Tobias Silvia
Published: January 2013

This article presents a literature review that explores the challenges for planning in urban regions in connection with the preservation of ecosystem services. It further presents some best practice examples for meeting these challenges. The demand for the provision of ecosystem services within urban regions changed during the transition from a largely agrarian society to an industrial society and, most recently, to a service society. Although in the past, provisioning services such as food production or the provision of raw material were decisive for urban development, today cultural services, e.g., clear views or nearby recreation areas, have become increasingly important. According to the literature, soil sealing is the greatest threat urbanization poses toward ecosystem services, as it compromises all of them. Spatially extensive cities with a high building density particularly inhibit regulating services like the regulation of temperature or water surface runoff. Conversely, scattered settlement patterns may lead to very small remnants of open space that cannot reasonably serve as natural habitat, agricultural land, or recreation area. The challenges for planning in urban regions are: 1) specifying regulations that define outer limits to the development of each settlement unit, 2) comprehensive planning with focal points for development, and limiting access and development at other places, and 3) compensating for new soil sealing by restoring nearby sealed areas. The article presents 3 best-practice examples that support these principles: designating areas with a particular soil quality that should not be built over, offering incentives for corporate planning in urban regions, and restoring a country road in connection with a motorway construction. Integr Environ Assess Manag 2013; 9: 243–251. © 2013 SETAC
QUALITY OF DRAINAGE WATER UNDER IRRIGATED COTTON IN VERTISOLS OF THE LOWER NAMOI VALLEY, NEW SOUTH WALES, AUSTRALIA
Authors: Weaver T. B. , Hulugalle N. R. , Ghadiri H. , Harden S.
Published: January 2013

Comparative research on the effects of soil and crop management practices in cotton farming systems on the quality of drainage water in irrigated Vertisols has not been reported in the literature. The objective of this study was to quantify drainage water quality in the subsoil (0.6, 0.9, 1.2 m) of sodic and non‐sodic Vertisols under selected crop rotations, viz. continuous cotton (Gossypium hirsutum L.), cotton–dolichos (Lablab purpureus L.) and cotton–wheat (Triticum aestivum L.). The experimental sites were located at the Australian Cotton Research Institute (ACRI) near Narrabri and on two commercial cotton farms near Wee Waa and Merah North in northern New South Wales, Australia. A cotton–wheat rotation was sown at Wee Waa and ACRI; wheat stubble was incorporated in the former and retained as in situ mulch in the latter. At Merah North, there were three cropping sequences; viz. continuous cotton, cotton–wheat, and cotton–dolichos sown between 1993 and 2000 in adjacent plots with identical land management histories. The three treatments were sown with cotton during the 2000–2001 and 2002–2003 growing seasons, wheat during the 2001 winter and sorghum during the 2001–2002 growing season with stubble being incorporated. Drainage water was sampled with 50‐mm diameter ceramic‐cup samplers from depths of 0.6, 0.9 and 1.2 m in six sites in each plot and irrigation water from the head ditch after irrigation between mid October and late February during the cotton‐growing seasons of 2000‐2001 and 2002–2003. Soil water extracted from the ceramic‐cup samplers was analysed for pHw, ECw, Cl‐, NO3‐‐N, K+, Ca2+, Mg2+ and Na+. Salt and nutrient concentrations in drainage water varied among sites, and reflected variations in soil properties, fallow length since the preceding crop, fallow rainfall and irrigation water quality. Salinity and SAR of drainage water were many times higher than those of irrigation water. Salinisation and sodification of shallow groundwater reserves under irrigated cotton in Vertisols are, therefore, a distinct possibility. Salinisation and sodification of the root zone may occur in cotton‐based rotations that result in poor subsoil structure and, thus, limited drainage even when irrigated with water of a quality that is generally accepted as being ‘reasonable’. Copyright © 2013 John Wiley & Sons, Ltd.
Traditional Machismo and Caballerismo as Correlates of Posttraumatic Stress Disorder, Psychological Distress, and Relationship Satisfaction in Hispanic Veterans
Authors: Herrera Catherine J. , Owens Gina P. , Mallinckrodt Brent
Published: January 2013

An online survey was used to examine 45 Hispanic male veterans’ traditional machismo and caballerismo as correlates of posttraumatic stress disorder (PTSD), psychological distress, and relationship satisfaction. Higher traditional machismo was associated with higher PTSD severity and distress and lower relationship satisfaction. Psychometric properties of the Traditional Machismo and Caballerismo Scale were explored.

Se utilizó una encuesta en línea para examinar el machismo y el caballerismo tradicionales de 45 veteranos hispanos varones, y su correlación con el trastorno de estrés post‐traumático (PTSD, por sus siglas en inglés), la angustia psicológica y la satisfacción en sus relaciones. Un mayor nivel de machismo tradicional se asoció con una mayor severidad del PTSD, así como con angustia y una menor satisfacción en las relaciones. Se exploraron las propiedades psicométricas de la Escala de Machismo y Caballerismo Tradicionales.
Racism‐Related Stress, General Life Stress, and Psychological Functioning Among Black American Women
Authors: Pieterse Alex L. , Carter Robert T. , Ray Kilynda V.
Published: January 2013

The relationship between general life stress, perceived racism, and psychological functioning was explored in a sample of 118 Black American women. Findings indicate that racism‐related stress was not a significant predictor of psychological functioning when controlling for general life stress. Perceived racism was positively associated with general life stress. Implications for practice and future research are discussed.

La relación entre el estrés general de la vida, el racismo percibido y el funcionamiento psicológico se exploraron en una muestra de 118 mujeres afroamericanas. Los resultados indican que el estrés relacionado con el racismo no fue un pronosticador significativo del funcionamiento psicológico cuando se controló estadísticamente para tomar en cuenta el estrés general de la vida. El racismo percibido estuvo asociado positivamente con el estrés general de la vida. Se discuten las implicaciones para la práctica e investigaciones futuras.
ADH based NAD+ regeneration in a microreactor
Authors: Šalić Anita , Ivanković Mia , Ferk Elvira , Zelić Bruno
Published: January 2013

BACKGROUND

The coenzyme NAD+ (nicotinamide adenine dinucleotide) is commonly used in biocatalytic oxidations catalysed by the enzyme alcohol dehydrogenase (ADH). As the price of the coenzyme NAD+ is extremely high, it is essential to regenerate the reduced form of the coenzyme back into the oxidized form. In this work the regeneration of the coenzyme NAD+ was carried out in a microreactor by reversible oxidation of ethanol to acetaldehyde with the ADH enzyme.

RESULTS

A 100% conversion of NADH was achieved for a residence time of just τ = 0.8 s when the concentration of acetaldehyde was in excess (ci,NADH = 5.5 mmol dm‐3, ci,acetaldehyde = 44 mmol dm‐3, γi,ADH = 0.2 g dm‐3, 75 mmol dm‐3 glycine‐pyrophosphate buffer pH = 9; T = 25°C). A 2D mathematical model for the description and prediction of microreactor performance was developed. Model simulations were validated using data from independent experiments.

CONCLUSION

The high conversions that were obtained for short residence times mean that the microreactors can be considered as good and efficient methods for coenzyme regeneration. © 2013 Society of Chemical Industry
An effective and rapid determination by MALDI/TOF/TOF of methionine sulphoxide content of ApoA‐I in type 2 diabetic patients
Authors: Seraglia Roberta , Sartore Giovanni , Marin Raffaella , Burlina Silvia , Manzato Enzo , Ragazzi Eugenio , Traldi Pietro , Lapolla Annunziata
Published: January 2013

Increased oxidation of low density lipoprotein (LDL) is characteristic of atherosclerosis. In this frame, high density lipoproteins (HDL) play an important role, being able to remove lipid peroxides (LPOs) and cholesterol from oxidized LDL, so exhibiting a protective role against atherosclerosis. A wide range of reactive compounds lead to the oxidation of methionine (Met) residues with the formation of methionine sulphoxide (MetO) in apolipoprotein A‐I (ApoA‐I). Consequently, the determination of MetO level can give both an evaluation of oxidative stress and the reduced capability of ApoA‐I in LPOs and cholesterol transport. For these reasons, the development of analytical methods able to determine the MetO level is surely of interest, and we report here the results obtained by MALDI mass spectrometry. Copyright © 2013 John Wiley & Sons, Ltd.
Characterization of superoxide dismutase 1 (SOD‐1) by electrospray ionization‐ion mobility mass spectrometry
Authors: Borges‐Alvarez Marta , Benavente Fernando , Vilaseca Marta , Barbosa José , Sanz‐Nebot Victoria
Published: January 2013

In this paper, we report nano‐electrospray ionization‐ion mobility mass spectrometry (nano‐ESI‐IM‐MS) characterization of bovine superoxide dismutase (SOD‐1) and human SOD‐1 purified from erythrocytes. SOD‐1 aggregates are characteristic of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease in humans that could be triggered by dissociation of the native dimeric enzyme (Cu2,Zn2‐dimer SOD‐1). In contrast to ESI‐MS, nano‐ESI‐IM‐MS allowed an extra dimension for ion separation, yielding three‐way mass spectra (drift time, mass‐to‐charge ratio and intensity). Drift time provided valuable structural information related to ion size, which proved useful to differentiate between the dimeric and monomeric forms of SOD‐1 under non denaturing conditions. In order to obtain detailed structural information, including the most relevant post‐translational modifications, we evaluated several parameters of the IM method, such as sample composition (10 mM ammonium acetate, pH 7) and activation voltages (trap collision energy and cone voltage). Neutral pH and a careful selection of the most appropriate activation voltages were necessary to minimize dimer dissociation, although human enzyme resulted less prone to dissociation. Under optimum conditions, a comparison between monomer‐to‐dimer abundance ratios of two small sets of blood samples from healthy control and ALS patients demonstrated the presence of a higher relative abundance of Cu,Zn‐monomer SOD‐1 in patient samples. Copyright © 2013 John Wiley & Sons, Ltd.
A sensitive and selective liquid chromatography−tandem mass spectrometry method for simultaneous determination of five isoquinoline alkaloids from Chelidonium majus L. in rat plasma and its application to a pharmacokinetic study
Authors: Zhou Qiuhong , Liu Youping , Wang Xin , Di Xin
Published: January 2013

Chelidonium majus L. is one of the most important medicinal plants of the family Papaveraceae. Its pharmacological effects have been primarily attributed to the presence of a number of alkaloids. In the present study, a sensitive and selective liquid chromatography−tandem mass spectrometry method for simultaneous determination of five isoquinoline alkaloids from Chelidonium majus L. was developed and validated. The analytes (protopine, chelidonine, coptisine, sanguinarine and chelerythrine), together with the internal standard (palmatine), were extracted from acidified rat plasma with ethyl acetate−dichloromethane (4:1, v/v). Chromatographic separation was carried out on a Diamonsil C18 column with an isocratic mobile phase consisting of acetonitrile and water (adjusted to pH 2.3 with formic acid) (30:70, v/v) at a flow rate of 0.4 ml/min. Mass spectrometric detection was performed by selected reaction monitoring mode via electrospray ionization source operating in positive ionization mode. The assay exhibited good linearity (r ≥ 0.9933) for all the analytes. The lower limits of quantification were 0.197−1.27 ng/ml using only 50 µl of plasma sample. The intra‐ and inter‐day precisions were less than 11.9%, and the accuracy was between −6.3% and 9.3%. The method was successfully applied to the pharmacokinetic study of the five alkaloids in rats after intragastric administration of Chelidonium majus L. extract. Copyright © 2013 John Wiley & Sons, Ltd.
Multiplex mass spectrometry imaging for latent fingerprints
Authors: Yagnik Gargey B. , Korte Andrew R. , Lee Young Jin
Published: January 2013

We have previously developed in‐parallel data acquisition of orbitrap mass spectrometry (MS) and ion trap MS and/or MS/MS scans for matrix‐assisted laser desorption/ionization MS imaging (MSI) to obtain rich chemical information in less data acquisition time. In the present study, we demonstrate a novel application of this multiplex MSI methodology for latent fingerprints. In a single imaging experiment, we could obtain chemical images of various endogenous and exogenous compounds, along with simultaneous MS/MS images of a few selected compounds. This work confirms the usefulness of multiplex MSI to explore chemical markers when the sample specimen is very limited. Copyright © 2013 John Wiley & Sons, Ltd.
Selective cleavage enhanced by acetylating the side chain of lysine
Authors: Fu Leixiaomeng , Chen Tingting , Xue Gaiqing , Zu Lily , Fang Weihai
Published: January 2013

Selective cleavage is of great interest in mass spectrometry studies as it can help sequence identification by promoting simple fragmentation pattern of peptides and proteins. In this work, the collision‐induced dissociation of peptides containing internal lysine and acetylated lysine residues were studied. The experimental and computational results revealed that multiple fragmentation pathways coexisted when the lysine residue was two amino acid residues away from N‐terminal of the peptide. After acetylation of the lysine side‐chain, ions were the most abundant primary fragment products and the Lys(Ac)–Gly amide bond became the dominant cleavage site via an oxazolone pathway. Acetylating the side‐chain of lysine promoted the selective cleavage of Lys–Xxx amide bond and generated much more information of the peptide backbone sequence. The results re‐evaluate the selective cleavage due to the lysine basic side‐chain and provide information for studying the post‐translational modification of proteins and other bio‐molecules containing Lys residues. Copyright © 2013 John Wiley & Sons, Ltd.
Rapid determination of polycyclic aromatic hydrocarbons in rainwater by liquid–liquid microextraction and LC with core‐shell particles column and fluorescence detection
Authors: Vinci Giuliana , Antonelli Marta L. , Preti Raffaella
Published: January 2013

Liquid–liquid microextraction coupled to LC with fluorescence detection for the determination of Environmental Protection Agency's 16 priority pollutant polycyclic aromatic hydrocarbons in rainwater has been developed. The optimization of the extraction method has involved several parameters, including the comparison between an ultrasonic bath and a magnetic stirrer as extractant apparatus, the choice of the extractant solvent, and the optimization of the extraction time. Liquid–liquid microextraction gave good results in terms of recoveries (from 73.6 to 102.8% in rainwater) and repeatability, with a very simple procedure and low solvent consumption. The reported chromatographic method uses a Core‐Shell technology column, with particle size <3 μm instead of classical 5‐μm particles column. The resulting backpressure was below 300 bar, allowing the use of a conventional HPLC system rather than the more expensive ultrahigh performance LC (UHPLC). An average decrease of 59% in run time and 75% in eluent consumption has been obtained, compared to classical HPLC methods, keeping good separation, sensitivity, and repeatability. The proposed conditions were successfully applied to the determinations of polycyclic aromatic hydrocarbons in genuine rainwater samples.
Priming a Cross‐Category Brand Alliance: The Moderating Role of Attribute Knowledge and Need for Cognition
Authors: Smarandescu Laura , Rose Randy , Wedell Douglas H.
Published: January 2013

Firms often enter cross‐category advertising brand alliance strategies with the goal to increase their market share by association with popular but noncompeting brand allies. However, firms are often not aware of the effects of these alliances on consumer perceptions of participating brands. This research explores the factors moderating brand attribute inferences following exposure to a cross‐category advertising brand alliance. It is proposed that attributes of a brand ally may serve as anchors that produce assimilation effects and move perceptions of a target brand toward the ally's attribute value, or as standards of comparison that produce contrast. This work provides evidence that attribute judgments in a cross‐category advertising brand alliance are moderated by attribute knowledge and individual differences in information processing motivation as reflected in self‐reported need for cognition (NFC) ratings.
Elastostatic response of a pile embedded in a transversely isotropic half‐space under transverse loading
Authors: Gharahi A. , Rahimian M. , Eskandari‐Ghadi M. , Pak R. Y. S.
Published: January 2013

In the framework of elastostatics, a mathematical treatment is presented for the boundary value problem of the interaction of a flexible cylindrical pile embedded in a transversely isotropic half‐space under transverse loadings. Taking the pile region as a stiffened subdomain of an extended half‐space, the formulation of the interaction problem is reduced to a Fredholm integral equation of the second kind. The necessary set of Green's functions for the transversely isotropic half‐space is obtained by means of a method of potentials. The resulting Green's functions are incorporated into a numerical procedure for the solution of the integral equation. The theoretical response of the pile is presented in terms of bending moment, displacement and slope profiles for a variety of transversely isotropic materials so that the effect of different anisotropy parameters can be meaningfully discussed. Copyright © 2013 John Wiley & Sons, Ltd.
Dysregulation of the mitosis–meiosis switch in testicular carcinoma in situ
Authors: Jørgensen Anne , Nielsen John E , Almstrup Kristian , Toft Birgitte Grønkær , Petersen Bodil Laub , Meyts Ewa Rajpert‐De
Published: January 2013

Testicular germ cell tumours (TGCT) of young adults arise from the intratubular precursor, carcinoma in situ (CIS). CIS cells are thought to be developmentally arrested and transformed fetal germ cells that survive through childhood and gain invasive capacity after puberty. Given that germ cell neoplasms arise frequently in undervirilized and dysgenetic gonads and the striking physiological difference between meiotic entry in ovaries (fetal life) versus testes (at puberty), this study aimed to investigate whether errors in regulation of meiosis may be implicated in the pathogenesis of CIS or its invasive progression to TGCT. The main focus was on a key sex differentiation and meiosis regulator, DMRT1, which has also been linked to TGCT risk in recent genetic association studies. Expression patterns of DMRT1 and other meiosis regulators (SCP3, DMC1, STRA8, CYP26B1, NANOS2, NANOS3) were investigated in pre‐ and post‐pubertal CIS samples and TGCT by quantitative RT–PCR and immunohistochemistry. The results demonstrated that meiosis markers and meiosis inhibitors were simultaneously expressed in CIS cells, in both pre‐ and post‐pubertal testis samples. DMRT1 was present in a restricted subset of CIS cells, which was relatively greater in pre‐pubertal (27%) compared to adult (2.6%) samples. In contrast to the majority of CIS cells, DMRT1‐positive CIS cells in adult testes were not proliferating. DMRT1 and most of the other meiosis regulators were absent or expressed at low levels in invasive TGCT, except in spermatocytic seminoma (not derived from CIS). In conclusion, this study indicates that meiosis signalling is dysregulated in CIS cells and that a key regulator of the mitosis–meiosis switch, DMRT1, is expressed in 'early‐stage' CIS cells but is down‐regulated with further invasive transformation. Whether this mixed meiosis signalling in CIS cells is caused by insufficient virilization of the fetal somatic niche or a partial post-pubertal maturation remains uncertain and requires further study.
Analysis of Benzonatate Overdoses Among Adults and Children from 1969–2010 by the United States Food and Drug Administration
Authors: McLawhorn Melinda W. , Goulding Margie R. , Gill Rajdeep K. , Michele Theresa M.
Published: January 2013

Study Objective

To augment the December 2010 United States Food and Drug Administration (FDA) Drug Safety Communication on accidental ingestion of benzonatate in children less than 10 years old by summarizing data on emergency department visits, benzonatate exposure, and reports of benzonatate overdoses from several data sources.

Design

Retrospective review of adverse‐event reports and drug utilization data of benzonatate.

Data Sources

The FDA Adverse Event Reporting System (AERS) database (1969–2010), the National Electronic Injury Surveillance System—Cooperative Adverse Drug Event Surveillance Project (NEISS‐CADES, 2004–2009), and the IMS commercial data vendor (2004–2009).

Patients

Any patient who reported an adverse event with benzonatate captured in the AERS or NEISS‐CADES database or received a prescription for benzonatate according to the IMS commercial data vendor.

Measurements and Main Results

Postmarketing adverse events with benzonatate were collected from the AERS database, emergency department visits due to adverse events with benzonatate were collected from the NEISS‐CADES database, and outpatient drug utilization data were collected from the IMS commercial data vendor. Of 31 overdose cases involving benzonatate reported in the AERS database, 20 had a fatal outcome, and five of these fatalities occurred from accidental ingestions in children 2 years of age and younger. The NEISS‐CADES database captured emergency department visits involving 12 cases of overdose from accidental benzonatate ingestions in children aged 1–3 years. Signs and symptoms of overdose included seizures, cardiac arrest, coma, brain edema or anoxic encephalopathy, apnea, tachycardia, and respiratory arrest and occurred in some patients within 15 minutes of ingestion. Dispensed benzonatate prescriptions increased by approximately 52% from 2004 to 2009.

Conclusion

Although benzonatate has a long history of safe use, accumulating cases of fatal overdose, especially in children, prompted the FDA to notify health care professionals about the risks of benzonatate overdose. Pharmacists may have a role in preventing benzonatate overdoses by counseling patients on signs and symptoms of benzonatate overdose, the need for immediate medical care, and safe storage and disposal of benzonatate.
Therapeutic Effect of Conivaptan Bolus Dosing in Hyponatremic Neurosurgical Patients
Authors: Marik Paul E. , Rivera Racquel
Published: January 2013

Study Objective

To determine the natremic response of a single 20‐mg bolus dose of conivaptan, an arginine vasopressin antagonist, in hyponatremic neurosurgical patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Design

Retrospective medical record review.

Setting

Neurosurgical intensive care unit of a tertiary care referral hospital.

Patients

Thirty‐two hyponatremic patients with SIADH who were admitted to the neurosurgical intensive care unit and received a single 20‐mg bolus dose of conivaptan between January and December 2011.

Measurements and Main Results

Each patient's natremic response over 48 hours was determined. The primary end point was an increase in serum sodium level of 4 mEq/L or greater over the first 24 hours. The mean ± SD baseline serum sodium level was 129.8 ± 3.4 mEq/L, which increased to 133.1 ± 3.2 mEq/L at 6 hours after administration of the bolus dose of conivaptan. The serum sodium level at 24 hours was 134.2 ± 3.2 mEq/L, indicating a 24‐hour natremic response of 4.3 ± 2.6 mEq/L (range 1–13 mEq/L) from baseline (p<0.001). Eighteen patients (56%) met the primary end point. The mean ± SD fluid balance over the first 24 hours was –783 ± 440 ml. The mean ± SD change in serum sodium level from 24 to 48 hours was 0.5 ± 1.3 mEq/L. No adverse effects or injection‐site reactions were noted. The patients who failed to reach the primary end point were treated with repeated doses of conivaptan plus other agents.

Conclusion

We recommend a single 20‐mg dose of conivaptan as the preferred initial approach to treating patients with SIADH who are in the neurosurgical intensive care unit. The 24‐hour natremic response should then dictate whether additional doses of conivaptan or other therapeutic interventions are required. We believe that such an approach is safe and will result in a controlled and predictable increase in the serum sodium concentration.
Brentuximab Vedotin: A CD30‐Directed Antibody‐Cytotoxic Drug Conjugate
Authors: Newland Ashley M. , Li Jenny X. , Wasco Lindsey E. , Aziz May T. , Lowe Denise K.
Published: January 2013

Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL), which is a subtype of non‐Hodgkin lymphoma, are relatively uncommon lymphoproliferative types of cancer. These malignancies are highly curable with initial treatment. Nonetheless, some patients are refractory to or relapse after first‐ and second‐line therapies, and outcomes for these patients are less promising. Brentuximab vedotin is a CD30‐directed antibody‐cytotoxic drug conjugate that has demonstrated efficacy in response rates (objective response rates and complete response) when given to patients with refractory or relapsed HL and sALCL. Although not compared directly in clinical trials, the response rates with brentuximab vedotin are higher than those of several current treatments for refractory or relapsed HL and sALCL. Adverse effects associated with brentuximab vedotin are considered manageable. Nonetheless, several serious adverse effects (e.g., neutropenia, peripheral sensory neuropathy, tumor lysis syndrome, Stevens‐Johnson syndrome, and progressive multifocal leukoencephalopathy, resulting in death) have been reported with its use. Despite a lack of survival and patient reported outcome data, the United States Food and Drug Administration (FDA) granted accelerated approval to brentuximab vedotin for the treatment of HL after failure of autologous stem cell transplantation or at least two combination chemotherapy regimens, and for sALCL after failure of at least one combination chemotherapy regimen. With this approval, brentuximab vedotin is the first FDA‐approved agent for the treatment of HL in over three decades and the first agent specifically indicated to treat sALCL. Results of ongoing prospective trials should determine if brentuximab vedotin has a survival benefit when compared directly with standard treatment and if brentuximab vedotin is safe and efficacious when given earlier in the disease process, or when used with other chemotherapy for the treatment of HL and sALCL or other CD30‐positive malignancies.
Prevalence of and Factors That Influence Board Certification Among Pharmacy Practice Faculty at United States Colleges and Schools of Pharmacy
Authors: Toussaint Kimberly A. , Watson Kristin , Marrs Joel C. , Sturpe Deborah A. , Anderson Sarah L. , Haines Stuart T.
Published: January 2013

Board certification is a means of demonstrating expertise above the minimum licensing standards. For many health care professionals, this credential is a necessity. As pharmacists become involved in more advanced patient care services, board certification becomes an essential component to ensuring quality care. The prevalence of United States pharmacy practice faculty members who are board certified, however, is unknown. In addition, to our knowledge, factors that serve to motivate or discourage faculty from obtaining board certification have not been previously described; thus, 900 pharmacy practice faculty members listed in the American Association of Colleges of Pharmacy (AACP) online directory were invited to complete an online survey regarding motivators and barriers for board certification. In addition, a list of board‐certified pharmacists, obtained from the Board of Pharmacy Specialties, was used to check the board certification status of all pharmacy practice faculty members listed in the AACP directory. In 2011, the prevalence of board certification among the 2867 pharmacy practice faculty members was 37% (1063 pharmacists), with the highest prevalence found among assistant professors (39.4%). A total of 322 faculty members (36% response rate) completed the survey; of these, 308 self‐identified as pharmacy practice faculty, and their responses were included in the analysis. Current board certification in pharmacy specialties was reported by 163 respondents (52.9%); 14 (4.5%) were previously certified. Among the 308 respondents, the most common perceived reason why pharmacy practice faculty become board certified was the desire to be recognized as an expert in the field (71.5%). Those who were currently board certified indicated personal growth as the most important reason (60.1%). Those previously certified indicated no perceived benefit as the most common reason for not recertifying (71.4%). Among those never certified, no perceived need (52.0%) or benefit (44.8%) were the most common reasons for not becoming certified; however, a majority of those never certified (68%) stated that they would become board certified if there was no associated cost and they were confident they would pass. To increase the prevalence of board certification in pharmacy practice faculty at U.S. schools and colleges of pharmacy, the benefits of this credential must be addressed at each institution. Steps should be taken to assist and encourage board certification.
Posaconazole Pharmacokinetics in a 2‐Year‐Old Boy with Rhino‐Cerebral‐Orbital Zygomycosis
Authors: Egelund Eric F. , Egelund Tosha A. , Ng John S. , Wassil Sarah K. , Peloquin Charles A.
Published: January 2013

Posaconazole is a triazole antifungal agent used as adjuvant or salvage therapy for the treatment of zygomycosis, an invasive fungal infection associated with high mortality. Oral posaconazole absorption is highly variable. We describe the pharmacokinetics of oral posaconazole in a 2‐year‐old boy with rhino‐cerebral‐orbital zygomycosis. Seven days after induction therapy for acute lymphoblastic leukemia, he was brought to the emergency department because of left eyelid swelling and was admitted to the hospital. Zygomycosis was diagnosed 12 days later. After we conducted a literature search and consulted with antifungal drug experts, a triple‐antifungal regimen consisting of liposomal amphotericin B, caspofungin, and posaconazole was started. Given the severity of the disease, we aimed for posaconazole plasma trough concentrations greater than 1.25 µg/ml; the dosage necessary to achieve this goal was posaconazole 200 mg 4 times/day. After a difficult 105‐day stay in the hospital and stabilization of the fungal infection, the patient was discharged. Caspofungin was discontinued at time of discharge, but the patient continued to receive amphotericin B lipid complex 7.5 mg/kg/day intravenously and posaconazole 200 mg orally 4 times/day. This is one of the few case reports describing posaconazole pharmacokinetics in a child younger than 8 years. In patients with extensive zygomycosis, a triple‐antifungal regimen, combined with therapeutic drug monitoring of posaconazole, may be helpful.
One‐step synthesis of a thienylenepyridazinylenethienylene‐based coil‐rod‐coil copolymer with enhanced emission and improved fluorescence stability
Authors: Wu Wei , Xu Haibo , Shen Dezhi , Qiu Tian , Fan Li‐Juan
Published: January 2013

A new coil‐rod‐coil copolymer is synthesized via Sonogashira coupling using one‐step methodology. The copolymer PEG‐OEPETPT‐PEG constitutes of poly(ethylene glycol) (PEG) as the coil block, and oligo[p‐(ethynylenephenyleneethynylene)‐alt‐(thienylenepyridazinylenethienylene)] (OEPETPT) as the rod segment. The conjugated polymer PEPETPT with the same conjugated building blocks is also synthesized for comparison. The structures of both polymers are confirmed by NMR, combined with other characterizations. PEG‐OEPETPT‐PEG has a 12 nm blue‐shift in the emission maximum compared with that of PEPETPT, and a higher quantum yield of fluorescence in THF. PEG‐OEPETPTE‐PEG tolerates up to 20% water content in H2O/THF mixed solvent without significantly changing the emission wavelength and intensity, while the fluorescence of PEPETPT is dramatically quenched by a very small quantity of water. Further photophysical studies about these two polymers indicate that the introduction of PEG coils onto the conjugated block retards the water‐induced‐aggregation and therefore improves the fluorescence stability of PEG‐OEPETPT‐PEG. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
Preparation and Performance of a HNIW/TNT Cocrystal Explosive
Authors: Yang Zongwei , Li Hongzhen , Huang Hui , Zhou Xiaoqing , Li Jinshan , Nie Fude
Published: January 2013

A novel cocrystal explosive composed of 2,4,6,8,10,12‐hexanitrohexaazaiso‐wurtzitane (HNIW) and 2,4,6‐trinitrotoluene (TNT) in a 1 : 1 molar ratio was effectively prepared by solvent/nonsolvent cocrystallization adopting dextrin as modified additive. The structure, thermal behavior, sensitivity, and detonation properties of HNIW/TNT cocrystal were studied. The morphology and structure of the cocrystal were characterized by scanning electron microscopy (SEM) and single crystal X‐ray diffraction (SXRD). SEM images showed that the cocrystal has a prism type morphology with an average size of 270 μm. SXRD revealed that the cocrystal crystallizes in the orthorhombic system, space group Pbca, and is formed by hydrogen bonding interactions. The properties of the cocrystal including sensitivity, thermal decomposition, and detonation performances were discussed in detail. Sensitivity studies showed that the cocrystal exhibits low impact and friction sensitivity, and largely reduces the mechanical sensitivity of HNIW. DSC and TG tests indicated that the heterogeneous exothermic decomposition of the cocrystal occurs in the temperature range from 170 °C to 265 °C with peak maxima at 220 °C and 250 °C and significantly increases the melting point of TNT by 54 °C. The cocrystal has excellent detonation properties with a detonation velocity of 8426 m s−1 and a calculated detonation pressure of 32.3 MPa at a charge density of 1.76 g cm−3, respectively. Moreover, the results suggested that the HNIW/TNT cocrystal not only has unique performance itself, but also effectively alters the properties of TNT and HNIW. Therefore, the cocrystal formed by HNIW and TNT could provide a new and effective method to modify the properties of certain compounds to yield enhanced explosives for further application.
High performance Zn–Sn–O thin film transistors with Cu source/drain electrode
Authors: Lee Chul‐Kyu , Park Se Yeob , Jung Hong Yoon , Lee Chang‐Kyu , Son Byeong‐Geun , Kim Hyo Jin , Lee Young‐Joo , Joo Young‐Chang , Jeong Jae Kyeong
Published: January 2013

Zn–Sn–O (ZTO) thin film transistors (TFTs) were fabricated with a Cu source/drain electrode. Although a reasonably high mobility (μFE) of 13.2 cm2/Vs was obtained for the ZTO TFTs, the subthreshold gate swing (SS) and threshold voltage (Vth) of 1.1 V/decade and 9.1 V, respectively, were inferior. However, ZTO TFTs with Ta film inserted as a diffusion barrier, exhibited improved SS and Vth values of 0.48 V/decade and 3.0 V, respectively as well as a high μFE value of 18.7 cm2/Vs. The improvement in the Ta‐inserted device was attributed to the suppression of Cu lateral diffusion into the ZTO channel region. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Collection, synthesis, and interpretation of evidence: a proof‐of‐concept study in COPD
Authors: Di Scala L. , Kerman J. , Neuenschwander B.
Published: January 2013

We present a clinical proof‐of‐concept (PoC) study in chronic obstructive pulmonary disease with the objective of assessing the bronchodilatory effect of an experimental drug as compared with an active control treatment. In such an exploratory Phase II setting, we discuss the formal inclusion of relevant historical information and tailored PoC criteria for the purpose of a more efficient use of the available evidence to support clinical decision making. We provide guidance with regard to practical and methodological aspects for assessing the relevance of the historical data, synthesizing the evidence via a meta‐analytic‐predictive approach, and defining transparent statistical PoC decision criteria that are aligned with the clinical context. The case study was implemented using the Bayesian approach, which offers an ideal framework for the early phases of drug development. Copyright © 2013 John Wiley & Sons, Ltd.
Sotalol as first‐line treatment for fetal tachycardia and neonatal follow‐up
Authors: van der Heijden L. B. , Oudijk M. A. , Manten G. T. R. , ter Heide H. , Pistorius L. , Freund M. W.
Published: January 2013

Objectives

In fetal tachycardia, pharmacological therapy with digoxin, flecainide and sotalol has been reported to be effective. In a recent retrospective multicenter study, sotalol was considered to be less effective than the other drugs in treatment of fetal supraventricular tachycardia (SVT). The aim of this study was to re‐evaluate the efficacy and safety of maternally administered sotalol in the treatment of fetal tachycardia.

Methods

This was a retrospective review of the records of 30 consecutive fetuses with tachycardia documented on M‐mode echocardiography between January 2004 and December 2010 at Wilhelmina Children's Hospital, a tertiary referral university hospital. Patients were subdivided into those diagnosed with supraventricular tachycardia and those with atrial flutter (AF) and presence of hydrops was noted. Other variables investigated included QTc interval measured on maternal electrocardiogram before and after initiation of antiarrhythmic therapy, fetal heart rhythm and heart rate pre‐ and postnatally, oral maternal drug therapy used, time to conversion to sinus rhythm (SR), percentage of fetuses converted following transplacental treatment, maternal adverse effects, presence or absence of tachycardia as noted on postnatal ECG, postnatal therapy or prophylaxis and neonatal outcome. Findings are discussed with reference to the literature.

Results

A total of 28 patients (18 with SVT, 10 with AF) were treated with sotalol as first‐line therapy. Fetal hydrops was present in six patients (five with SVT, one with AF). All hydropic patients converted antenatally to SR (67% with sotalol as a single‐drug therapy, 33% after addition of flecainide). Of the non‐hydropic patients, 91% converted to SR (90% with sotalol only, 10% after addition of flecainide or digoxin). In 9% (with AF) rate control was achieved. There was no mortality. No serious drug‐related adverse events were observed. Postnatally, rhythm disturbances were detected in 10 patients, two of whom still had AF. In eight, SVT was observed within 3 weeks postnatally, and in five of these within 72 hours.

Conclusions

Sotalol can be recommended as the drug of first choice for treatment of fetal AF and has been shown to be an effective and safe first‐line treatment option for SVT, at least in the absence of hydrops. Postnatal maintenance therapy after successful prenatal therapy is not necessarily indicated, as the risk of recurrence is low beyond 72 hours of age. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.