bluuebunny/crossref_metadata_2025 huggingface dataset:
Identity Building in Social Marketing
Authors: Engelberg Moshe , Kirby Susan D.
Published: April 2010

The corporate community has long been engaged in the process of identity building. Now, many social organizations recognize that identity building can be used to develop and promote programs, tactics, strategies and organizational missions. Identity building can help strengthen support for social organizations, improve effectiveness and use of programs by target audiences, help organizations determine the most unique and valuable benefits they can offer their stakeholders, and provide guidance for delivering those benefits. The research and development required for effective identity building is often summarized in an identity strategy, or platform, much like a marketing plan.

This article is intended to help social marketers: 1) articulate how a strong identity can help organizations stand out in a competitive marketplace; 2) understand the key concepts of identity building within a social marketing context; 3) explain the elements that constitute an identity platform; and 4) describe the critical steps to develop an effective identity platform.
Strategies and Practices in Community—Based Campaigns Promoting Nutrition and Physical Activity
Authors: Alcalay Rina , Bell Robert A.
Published: April 2010

The strategies and practices employed in 50 community-based nutrition and physical activity interventions are reviewed from the perspective of a four-stage social marketing model. Goals and objectives established at the research and planning stage were infrequently grounded in data and theory. At the strategy design stage, concept/message pretesting was uncommon. Most campaigns disseminated material products through several channels and activities. At the implementation stage, community members were regularly enlisted as collaborators and a majority of campaigns identified sustainability as a long-term goal. In the evaluation stage, summative research was most often based on quasi-experimental methods. Self-reported knowledge and behavior effects were often assessed; morbidity and mortality campaign effects were rarely considered. Suggestions are offered for improving the design and execution of future interventions.
Clarifying Trade Costs: Maritime Transport and Its Effect on Agricultural Trade
Authors: Korinek Jane , Sourdin Patricia
Published: April 2010

Greater attention has been given to trade costs in both the empirical trade literature and in theoretical models of international trade in recent years, with interest increasingly being directed towards the role of nonpolicy barriers such as transport costs. However, if distance is a proxy for transport and other trade costs, then the true effect of transport costs is impossible to determine. We attempt to remedy this by utilizing the newly compiled Organisation for Economic Co‐operation and Development Maritime Transport Cost database to investigate the role that maritime freight costs play in determining ocean‐shipped agricultural imports. We find that transport costs robustly and significantly negatively impact agricultural imports, even after controlling for shipping distance.
The Long‐Run and Short‐Run Impact of Captive Supplies on the Spot Market Price: An Agent‐Based Artificial Market
Authors: Zhang Tong , Brorsen B. Wade
Published: April 2010

An agent‐based model is developed that matches the results of Xia and Sexton (2004) as well as our generalization of their model. We relax Xia and Sexton's assumption of no supply response by captive feeders, which reduces the price‐depressing effect of captive supplies. Finally, the agent‐based model is used to simulate packers choosing both captive supply quantities and spot market quantities. Packers in the relaxed agent‐based model choose no captive supplies and thus reach the Cournot solution. The research narrows the gap between theoretical models and the empirical work on captive supplies that shows little effect on prices, but a gap remains.
Map dynamics versus dynamics of associated delay reaction–diffusion equations with a Neumann condition
Authors: Yi Taishan , Zou Xingfu
Published: April 2010

In this paper, we consider a class of delay reaction–diffusion equations (DRDEs) with a parameterε>0. A homogeneous Neumann boundary condition and non-negative initial functions are posed to the equation. By letting, such an equation is formally reduced to a scalar difference equation (or map dynamical system). The main concern is the relation of the absolute (or delay-independent) global stability of a steady state of the equation and the dynamics of the nonlinear map in the equation. By employing the idea of attracting intervals for solution semiflows of the DRDEs, we prove that the globally stable dynamics of the map indeed ensures the delay-independent global stability of a constant steady state of the DRDEs. We also give a counterexample to show that the delay-independent global stability of DRDEs cannot guarantee the globally stable dynamics of the map. Finally, we apply the abstract results to the diffusive delay Nicholson blowfly equation and the diffusive Mackey–Glass haematopoiesis equation. The resulting criteria for both model equations are amazingly simple and are optimal in some sense (although there is no existing result to compare with for the latter).
Coupled dynamics of populations supported by discrete sites and their continuum limit
Authors: Field Timothy R. , Tough Robert J. A.
Published: April 2010

The illumination of single population behaviour subject to the processes of birth, death and immigration has provided a basis for the discussion of the non-Gaussian statistical and temporal correlation properties of scattered radiation. As a first step towards the modelling of its spatial correlations, we consider the populations supported by an infinite chain of discrete sites, each subject to birth, death and immigration and coupled by migration between adjacent sites. To provide some motivation, and illustrate the techniques we will use, the migration process for a single particle on an infinite chain of sites is introduced and its diffusion dynamics derived. A certain continuum limit is identified and its properties studied via asymptotic analysis. This forms the basis of the multi-particle model of a coupled population subject to single site birth, death and immigration processes, in addition to inter-site migration. A discrete rate equation is formulated and its generating function dynamics derived. This facilitates derivation of the equations of motion for the first- and second-order cumulants, thus generalizing the earlier results of Bailey through the incorporation of immigration at each site. We present a novel matrix formalism operating in the time domain that enables solution of these equations yielding the mean occupancy and inter-site variances in the closed form. The results for the first two moments at a single time are used to derive expressions for the asymptotic time-delayed correlation functions, which relates to Glauber’s analysis of an Ising model. The paper concludes with an analysis of the continuum limit of the birth–death–immigration–migration process in terms of a path integral formalism. The continuum rate equation and evolution equation for the generating function are developed, from which the evolution equation of the mean occupancy is derived, in this limit. Its solution is provided in closed form.
A note on configurational anisotropy
Authors: Slastikov Valeriy V.
Published: April 2010

We investigate an effect of
configurational anisotropy
in highly symmetric soft ferromagnetic nanoparticles. Using the micromagnetic variational principle and methods of Γ-convergence, we show that in ferromagnetic

generalized right prisms with

symmetry

,

1

there is a finite number of preferred magnetization directions and that these directions are independent of the shape of the magnet. This result provides a rigorous justification of work by Cowburn and Welland.
Infected subdural haematoma due to Salmonella
enterica serovar Typhimurium in an adult
Authors: Hayakawa Kayoko , Oikawa Akihiro , Takeda Naoto , Sasaki Kuri , Hatakeyama Shuji
Published: April 2010

A 65-year-old man with a history of alcoholism and gastrectomy was diagnosed with an infected subdural haematoma due to Salmonella
enterica serovar Typhimurium. He was successfully treated with surgical drainage and intravenous ceftriaxone. To our knowledge, there has been no detailed case report in English of infected subdural haematoma or subdural empyema due to Salmonella Typhimurium in adults.
Using comparative genome analysis to identify problems in annotated microbial genomes
Authors: Poptsova Maria S. , Gogarten J. Peter
Published: April 2010

Genome annotation is a tedious task that is mostly done by automated methods; however, the accuracy of these approaches has been questioned since the beginning of the sequencing era. Genome annotation is a multilevel process, and errors can emerge at different stages: during sequencing, as a result of gene-calling procedures, and in the process of assigning gene functions. Missed or wrongly annotated genes differentially impact different types of analyses. Here we discuss and demonstrate how the methods of comparative genome analysis can refine annotations by locating missing orthologues. We also discuss possible reasons for errors and show that the second-generation annotation systems, which combine multiple gene-calling programs with similarity-based methods, perform much better than the first annotation tools. Since old errors may propagate to the newly sequenced genomes, we emphasize that the problem of continuously updating popular public databases is an urgent and unresolved one. Due to the progress in genome-sequencing technologies, automated annotation techniques will remain the main approach in the future. Researchers need to be aware of the existing errors in the annotation of even well-studied genomes, such as Escherichia coli, and consider additional quality control for their results.
Microbial dynamics in upflow anaerobic sludge blanket (UASB) bioreactor granules in response to short-term changes in substrate feed
Authors: Kovacik William P. , Scholten Johannes C. M. , Culley David , Hickey Robert , Zhang Weiwen , Brockman Fred J.
Published: April 2010

The upflow anaerobic sludge blanket (UASB) reactor is a microcosm for the methanogenic degradation of organic matter in anaerobic environments, and depends on the auto-formation of dense 3D biofilms of 1–3 mm in diameter, referred to as granular sludge (biogranules). Past research has shown that UASB and other methanogenic reactors are extremely stable functionally, but the underlying basis of the functional stability is not well understood. In this study, microbial dynamics in the communities residing in UASB biogranules were analysed to determine responses to short-term perturbations (change in reactor feed). The reactor was fed with simulated brewery wastewater (SBWW) for 1.5 months (phase 1), acetate/sulfate for 2 months (phase 2), acetate alone for 3 months (phase 3) and then a return to SBWW for 2 months (phase 4). Analysis of 16S rRNA, methanogen-associatedmcrAand sulfate reducer-associateddsrABgene-based-clone libraries showed a relatively simple community composed mainly of the methanogenic archaea (MethanobacteriumandMethanosaeta), members of the green non-sulfur (Chloroflexi) group of bacteria andSyntrophobacter,Spirochaeta,AcidobacteriaandCytophaga-related bacterial sequences. ThemcrAclone libraries were dominated throughout byMethanobacterium- andMethanospirillum-related sequences. Although the reactor performance remained relatively stable throughout the experiment, community diversity levels generally decreased for all libraries in response to a change from SBWW to acetate alone feed. There was a large transitory increase noted in 16S diversity at the 2 month sampling on acetate alone, entirely related to an increase in bacterial diversity. Upon return to SBWW conditions in phase 4, all diversity measures returned to near phase 1 levels. Our results demonstrated that microbial communities, even highly structured ones such as in UASB biogranules, are very capable of responding to rapid and major changes in their environment.
PHR1, a pH-regulated gene of Candida albicans encoding a glucan-remodelling enzyme, is required for adhesion and invasion
Authors: Calderon Julia , Zavrel Martin , Ragni Enrico , Fonzi William A. , Rupp Steffen , Popolo Laura
Published: April 2010

The fungal cell wall plays a crucial role in host–pathogen interactions. Its formation is the result of the coordinated activity of several extracellular enzymes, which assemble the constituents, and remodel and hydrolyse them in the extracellular space.Candida albicansPhr1 and Phr2 proteins belong to family GH72 of theβ-(1,3)-glucanosyltransferases and play a crucial role in cell wall assembly.PHR1andPHR2, homologues ofSaccharomyces cerevisiae GAS1, are differently regulated by extracellular pH.PHR1is expressed when ambient pH is 5.5 or higher, whereasPHR2has the reverse expression pattern. Their deletion causes a pH-conditional defect in morphogenesis and virulence. In this work we explored whetherPHR1deletion affects the ability ofC. albicansto adhere to and invade human epithelia.PHR1null mutants exhibited a marked reduction in adhesion to both abiotic surfaces and epithelial cell monolayers. In addition, the mutant was unable to penetrate and invade reconstituted human epithelia. Transcription profiling of selected hyphal-specific and adhesin-encoding genes indicated that in thePHR1null mutant,HWP1andECE1transcript levels were similarly reduced in both adhesion and suspension conditions. These results, combined with microscopy analysis of the septum position, suggest thatPHR1is not required for the induction of hyphal development but plays a key role in the maintenance of hyphal growth. Thus, theβ-(1,3)-glucan processing catalysed by Phr1p is of fundamental importance in the maintenance of the morphological state on which the adhesive and invasive properties ofC. albicansgreatly depend.
Mutations affecting the extreme C terminus of Escherichia coli haemolysin A reduce haemolytic activity by altering the folding of the toxin
Authors: Jumpertz Thorsten , Chervaux Christian , Racher Kathleen , Zouhair Maria , Blight Mark A. , Holland I. Barry , Schmitt Lutz
Published: April 2010

Escherichia coli haemolysin A (HlyA), an RTX toxin, is secreted probably as an unfolded intermediate, by the type I (ABC transporter-dependent) pathway, utilizing a C-terminal secretion signal. However, the mechanism of translocation and post-translocation folding is not understood. We identified a mutation (hlyA99) at the extreme C terminus, which is dominant in competition experiments, blocking secretion of the wild-type toxin co-expressed in the same cell. This suggests that unlike recessive mutations which affect recognition of the translocation machinery, the hlyA99 mutation interferes with some later step in secretion. Indeed, the mutation reduced haemolytic activity of the toxin and the activity of β-lactamase when the latter was fused to a C-terminal 23 kDa fragment of HlyA carrying the hlyA99 mutation. A second mutant (hlyAdel6), lacking the six C-terminal residues of HlyA, also showed reduced haemolytic activity and neither mutant protein regained normal haemolytic activity in in vitro unfolding/refolding experiments. Tryptophan fluorescence spectroscopy indicated differences in structure between the secreted forms of wild-type HlyA and the HlyA Del6 mutant. These results suggested that the mutations affected the correct folding of both HlyA and the β-lactamase fusion. Thus, we propose a dual function for the HlyA C terminus involving an important role in post-translocation folding as well as targeting HlyA for secretion.
Evolutionarily conserved replication timing profiles predict long-range chromatin interactions and distinguish closely related cell types
Authors: Ryba Tyrone , Hiratani Ichiro , Lu Junjie , Itoh Mari , Kulik Michael , Zhang Jinfeng , Schulz Thomas C. , Robins Allan J. , Dalton Stephen , Gilbert David M.
Published: April 2010

To identify evolutionarily conserved features of replication timing and their relationship to epigenetic properties, we profiled replication timing genome-wide in four human embryonic stem cell (hESC) lines, hESC-derived neural precursor cells (NPCs), lymphoblastoid cells, and two human induced pluripotent stem cell lines (hiPSCs), and compared them with related mouse cell types. Results confirm the conservation of coordinately replicated megabase-sized “replication domains” punctuated by origin-suppressed regions. Differentiation-induced replication timing changes in both species occur in 400- to 800-kb units and are similarly coordinated with transcription changes. A surprising degree of cell-type-specific conservation in replication timing was observed across regions of conserved synteny, despite considerable species variation in the alignment of replication timing to isochore GC/LINE-1 content. Notably, hESC replication timing profiles were significantly more aligned to mouse epiblast-derived stem cells (mEpiSCs) than to mouse ESCs. Comparison with epigenetic marks revealed a signature of chromatin modifications at the boundaries of early replicating domains and a remarkably strong link between replication timing and spatial proximity of chromatin as measured by Hi-C analysis. Thus, early and late initiation of replication occurs in spatially separate nuclear compartments, but rarely within the intervening chromatin. Moreover, cell-type-specific conservation of the replication program implies conserved developmental changes in spatial organization of chromatin. Together, our results reveal evolutionarily conserved aspects of developmentally regulated replication programs in mammals, demonstrate the power of replication profiling to distinguish closely related cell types, and strongly support the hypothesis that replication timing domains are spatially compartmentalized structural and functional units of three-dimensional chromosomal architecture.
Studies of a Biochemical Factory: Tomato Trichome Deep Expressed Sequence Tag Sequencing and Proteomics
Authors: Schilmiller Anthony L. , Miner Dennis P. , Larson Matthew , McDowell Eric , Gang David R. , Wilkerson Curtis , Last Robert L.
Published: April 2010

Shotgun proteomics analysis allows hundreds of proteins to be identified and quantified from a single sample at relatively low cost. Extensive DNA sequence information is a prerequisite for shotgun proteomics, and it is ideal to have sequence for the organism being studied rather than from related species or accessions. While this requirement has limited the set of organisms that are candidates for this approach, next generation sequencing technologies make it feasible to obtain deep DNA sequence coverage from any organism. As part of our studies of specialized (secondary) metabolism in tomato (Solanum lycopersicum) trichomes, 454 sequencing of cDNA was combined with shotgun proteomics analyses to obtain in-depth profiles of genes and proteins expressed in leaf and stem glandular trichomes of 3-week-old plants. The expressed sequence tag and proteomics data sets combined with metabolite analysis led to the discovery and characterization of a sesquiterpene synthase that produces β-caryophyllene and α-humulene from E,E-farnesyl diphosphate in trichomes of leaf but not of stem. This analysis demonstrates the utility of combining high-throughput cDNA sequencing with proteomics experiments in a target tissue. These data can be used for dissection of other biochemical processes in these specialized epidermal cells.
Real-space calculation of powder diffraction patterns on graphics processing units
Authors: Gelisio Luca , Azanza Ricardo Cristy Leonor , Leoni Matteo , Scardi Paolo
Published: April 2010

A new software for calculating the powder diffraction pattern of nano-sized objects has been developed to run on graphics processing units (GPUs). This solution is well suited to the inherently parallel structure of the Debye function, which is the core of the computation algorithm. Advantages and perspectives in view of the improving performance of GPUs are illustrated by several representative case studies.
Simulating and evaluating small-angle X-ray scattering of micro-voids in polypropylene during mechanical deformation
Authors: Fischer Stefan , Diesner Tobias , Rieger Bernhard , Marti Othmar
Published: April 2010

Micro-voids that evolve during mechanical deformation in polypropylene have been characterized by small-angle X-ray scattering. Such voids can be modelled as randomly distributed cylinders which are oriented along the stretching direction, showing a log-normal size distribution. The model and simulation results are presented here. Advantages and disadvantages of the approach, the validity of the model, and important considerations for data evaluation are discussed. Data analysis of two-dimensional scattering images has been performed using a fully automatedMATLABroutine by direct model fitting to scattering images.
New approach to twin interfaces of modulated martensite
Authors: Li Zongbin , Zhang Yudong , Esling Claude , Zhao Xiang , Wang Yandong , Zuo Liang
Published: April 2010

In Ni–Mn–Ga ferromagnetic shape memory alloys, the crystallographic nature of martensitic variant interfaces is one of the key factors governing the variant reorientation through field-induced interface motion and hence the shape memory performance. So far, the crystal structure studies of these materials – conducted by means of transmission electron microscopy – have suffered from uncertainties in determining the number of unit cells of modulated superstructure, and consequently improper interpretations of orientation correlations of martensitic variants. In this paper a new approach is presented for comprehensive analysis of crystallographic and morphological information of modulated martensite, using automated electron backscatter diffraction. As a first attempt, it has been applied for the unambiguous determination of the orientation relationships of adjacent martensitic variants and their twin interface characters in an incommensurate 7M modulated Ni–Mn–Ga alloy, from which a clear and full-featured image of the crystallographic nature of constituent twin interfaces is built up. Certainly, this new approach will make it feasible not only to generalize the statistical analysis of martensitic variant distributions for various materials with modulated superstructure, but also to give insight into the crystallographic characteristics of martensitic variant interfaces and the variant reorientation mechanism of new advanced materials for interface engineering.
Crystal structure solution from experimentally determined atomic pair distribution functions
Authors: Juhás P. , Granlund L. , Gujarathi S. R. , Duxbury P. M. , Billinge S. J. L.
Published: April 2010

An extension of the Liga algorithm for structure solution from atomic pair distribution functions (PDFs), to handle periodic crystal structures with multiple elements in the unit cell, is described. The procedure is performed in three separate steps. First, pair distances are extracted from the experimental PDF. In the second step the Liga algorithm is used to find unit-cell sites consistent with these pair distances. Finally, the atom species are assigned over the cell sites by minimizing the overlap of their empirical atomic radii. The procedure has been demonstrated on synchrotron X-ray PDF data from 16 test samples. The structure solution was successful for 14 samples, including cases with enlarged supercells. The algorithm success rate and the reasons for the failed cases are discussed, together with enhancements that should improve its convergence and usability.
Autoindexing with outlier rejection and identification of superimposed lattices
Authors: Sauter Nicholas K. , Poon Billy K.
Published: April 2010

Constructing a model lattice to fit the observed Bragg diffraction pattern is straightforward for perfect samples, but indexing can be challenging when artifacts are present, such as poorly shaped spots, split crystals giving multiple closely aligned lattices and outright superposition of patterns from aggregated microcrystals. To optimize the lattice model against marginal data, refinement can be performed using a subset of the observations from which the poorly fitting spots have been discarded. Outliers are identified by assuming a Gaussian error distribution for the best-fitting spots and points diverging from this distribution are culled. The set of remaining observations produces a superior lattice model, while the rejected observations can be used to identify a second crystal lattice, if one is present. The prevalence of outliers provides a potentially useful measure of sample quality. The described procedures are implemented for macromolecular crystallography within the autoindexing programlabelit.index(http://cci.lbl.gov/labelit).
A simplified invariant line analysis for face-centred cubic/body-centred cubic precipitation systems
Authors: Liu Hongwei , Waclawik Eric R. , Luo Chengping
Published: April 2010

Several phenomenological crystallographic theories, including the invariant line model, O-line analysis and Δgparallelism rules, have been proposed and then successfully applied to the interpretation of crystallographic features for most face-centred cubic/body-centred cubic precipitation systems. However, the application of these methods requires the use of extra criteria and multiple rotations. A simplified invariant line analysis is proposed in this paper, to simplify the above theories from the well known confusions of additional criteria and multiple rotation around specific axes. One-step rotation dispenses with extra criteria or any input orientation relationship and so can deduce an invariant line when a Burgers vector is parallel to the habit plane. This simplified analysis makes the application of the theory more understandable, where it anticipates the invariant line, the habit plane, the orientation relationship between the matrix and the precipitate, and the distance between dislocations for which the Burgers vector is not inclined. The predictions are simplified, highly efficient and coincide well with experimental observations from lath-shaped precipitates in Cu–Cr and Ni–Cr alloys, as well as with the theoretical results obtained by O-line theory and Δgparallelism rules.
Determining grain resolved stresses in polycrystalline materials using three-dimensional X-ray diffraction
Authors: Oddershede Jette , Schmidt Søren , Poulsen Henning Friis , Sørensen Henning Osholm , Wright Jonathan , Reimers Walter
Published: April 2010

An algorithm is presented for characterization of the grain resolved (type II) stress states in a polycrystalline sample based on monochromatic X-ray diffraction data. The algorithm is a robust 12-parameter-per-grain fit of the centre-of-mass grain positions, orientations and stress tensors including error estimation and outlier rejection. The algorithm is validated by simulations and by two experiments on interstitial free steel. In the first experiment, using only a far-field detector and a rotation range of 2 × 110°, 96 grains in one layer were monitored during elastic loading and unloading. Very consistent results were obtained, with mean resolutions for each grain of approximately 10 µm in position, 0.05° in orientation, and 8, 20 and 13 × 10−5in the axial, normal and shear components of the strain, respectively. The corresponding mean deviations in stress are 30, 50 and 15 MPa in the axial, normal and shear components, respectively, though some grains may have larger errors. In the second experiment, where a near-field detector was added, ∼2000 grains were characterized with a positional accuracy of 3 µm.
Hyperkeratotic variant of porokeratosis Mibelli with dermal amyloid deposits
Authors: UENISHI Toshiaki , TERAMURA Kazuya , KITAMURA Masato , FUJII Norikazu , NAKANISHI Gen , TANAKA Toshihiro , UEHARA Masami
Published: April 2010

We report a case of hyperkeratotic variant of porokeratosis Mibelli with dermal amyloid deposits. A 66‐year‐old man presented with multiple brownish keratotic lesions on the lower extremities, a verrucous nodule on the third toe of the left foot and brownish verrucous plaques on the buttocks for several years. Histopathological examination of the hyperkeratotic plaque in the right gluteal region revealed extreme hyperkeratosis and cornoid lamella. In the papillary dermis, there were prominent eosinophilic amorphous materials which were positive to Dylon staining. Treatment with oral etretinate resulted in a remission of the skin lesions in this case.
Sarcoidosis during infliximab therapy for Crohn’s disease
Authors: TAKAHASHI Hidetoshi , KANETA Kazuhiro , HONMA Masaru , ISHIDA‐YAMAMOTO Akemi , ASHIDA Tomonori , KOHGO Yutaka , OHSAKI Yoshinobu , IIZUKA Hajime
Published: April 2010

Tumor necrosis factor‐α (TNF‐α) antagonists are effective for inflammatory diseases, such as Crohn’s disease, rheumatoid arthritis (RA) and psoriasis. Although TNF‐α antagonists are also useful for sarcoidosis, paradoxical occurrence of sarcoidosis or sarcoidal reaction may be observed. We report a Crohn’s disease patient, who developed sarcoidosis during infliximab therapy. A 35‐year‐old man had been receiving infliximab for 7 months for Crohn’s disease. He developed cough and fever, accompanied by an infiltrated erythematous plaque on his right knee. The chest radiography, skin biopsy and laboratory findings were all consistent with sarcoidosis.
Three cases of embolia cutis medicamentosa (Nicolau’s syndrome)
Authors: MARANGI Giovanni Francesco , GIGLIOFIORITO Pierluigi , TOTO Vito , LANGELLA Marika , PALLARA Tiziano , PERSICHETTI Paolo
Published: April 2010

Embolia cutis medicamentosa, also known as Nicolau’s syndrome, is a rare complication due to i.m. injections. Its real incidence is actually underestimated. Many drugs have been associated with it, but at the time only a few studies showed a related pathogenetic mechanism. Symptoms consist of immediate local pain, edema and cutaneous, subcutaneous and even muscular necrosis occurring in the first 48 h. The type of treatment depends mostly on time of diagnosis. A medical resolution can be achieved through heparin and cortisone injections within the first 48 h. Surgical debridement has to be considered as the main treatment in case of late diagnosis. We present three cases of Nicolau’s syndrome presenting to us in a short period of time that we treated with surgical debridement.
Clinical trial: esomeprazole for moderate‐to‐severe nighttime heartburn and gastro‐oesophageal reflux disease‐related sleep disturbances
Authors: Johnson D. , Crawley J. A. , Hwang C. , Brown K.
Published: April 2010

Aliment Pharmacol Ther 2010; 32: 182–190

Background  Nighttime heartburn, common among patients with gastro‐oesophageal reflux disease (GERD), is associated with substantial clinical effects. GERD‐related sleep disturbances are underappreciated and undertreated.

Aim  To evaluate the efficacy of esomeprazole on GERD‐related nighttime heartburn and associated sleep disturbances.

Methods  In this multicentre, randomized, double‐blind, placebo‐controlled study, patients with moderate‐to‐severe nighttime heartburn and GERD‐related sleep disturbances (endoscopies not required) received esomeprazole 20 mg or placebo each morning for 4 weeks. Heartburn symptoms and GERD‐related sleep disturbances were evaluated using the validated Pittsburgh Sleep Quality Index and validated Work Productivity and Activity Impairment Questionnaire.

Results  The analysis included 262 patients (esomeprazole, n = 137; placebo, n = 125). Significantly more patients receiving esomeprazole achieved nighttime heartburn relief (primary end point) than those receiving placebo (34.3% vs. 10.4%; P < 0.0001). Secondary end points such as relief of GERD‐related sleep disturbances (P = 0.006), days without GERD‐related sleep disturbances (P = 0.0003) and complete resolution of sleep disturbances (P < 0.0001) favoured esomeprazole over placebo. Sleep quality, work productivity and regular daily activities also improved significantly with esomeprazole vs. placebo.

Conclusions  Esomeprazole 20 mg is effective for patients with moderate‐to‐severe nighttime heartburn and GERD‐related sleep disturbances, improving heartburn symptoms, sleep quality, work productivity and functionality.
Prevalence of potentially hazardous drug interactions amongst Australian veterans
Authors: Roughead Elizabeth E. , Kalisch Lisa M. , Barratt John D. , Gilbert Andrew L.
Published: April 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Up to 21% of adverse drug event related hospital admissions are due to drug interactions. Clinical significance of drug interactions varies.

• Studies which only identified drug interactions of potentially major clinical significance found lower prevalence, of between 2 and 16%.

• Prevalence of drug interactions defined ‘potentially hazardous’ has had limited study, with no publications identified for the Australian population.

WHAT THIS STUDY ADDS

• In the study population of 287 074, 1.5% of subjects were dispensed potentially hazardous interacting drug pairs.

• However, limited to populations on specific medicines, it was found that for patients dispensed verapamil, methotrexate, amiodarone, lithium, warfarin, cyclosporin and itraconazole, potentially hazardous interactions occurred at a rate greater than 5%.

• These patients should be the focus of medication review programmes to avoid potentially serious adverse drug events.

BACKGROUND

Up to 21% of adverse drug event‐related hospital admissions are due to drug interactions. Clinical significance of drug interactions varies, and drug interactions defined ‘potentially hazardous’ are more likely to contribute to morbidity and mortality.

AIM

The aim of this study was to assess the prevalence of potentially hazardous drug interactions in an elderly Australian veteran population.

METHODS

This study assessed the prevalence of potentially hazardous drug interactions, where hazardous was defined in three or more international drug interaction references, using Repatriation Pharmaceutical Benefits Scheme pharmacy claims data. Analysis was limited to patients who received regular concurrent dispensings of potentially hazardous interacting medicines.

RESULTS

Of the 287 074 subjects included in the study, 1.5% were dispensed potentially hazardous interacting drug pairs. For patients dispensed cyclosporin, concomitant use of a statin was common (47%); as was statin use with those dispensed itraconazole (31%). Of those dispensed methotrexate, 24% also received a non‐steroidal anti‐inflammatory drug; of those on lithium, 18% also received an ACE inhibitor or angiotensin 2 receptor blocker; of those on warfarin, 7.2% and 5.9% were co‐dispensed an non‐steroidal anti‐inflammatory drugs or antiplatelets respectively; for those on verapamil, 5.3% were co‐dispensed a beta‐blocker, while for those on amiodarone 6.2% were co‐dispensed digoxin.

CONCLUSIONS

Overall prevalence of potentially serious drug interactions appears to be low in the Australian veteran population. However, patients taking cyclosporine, itraconazole, methotrexate, lithium, warfarin, verapamil and amiodarone appear to be most at risk and their medicine use should be regularly reviewed to prevent potentially hazardous drug interactions.
Association of carboxylesterase 1A genotypes with irinotecan pharmacokinetics in Japanese cancer patients
Authors: Sai Kimie , Saito Yoshiro , Tatewaki Naoko , Hosokawa Masakiyo , Kaniwa Nahoko , Nishimaki‐Mogami Tomoko , Naito Mikihiko , Sawada Jun‐ichi , Shirao Kuniaki , Hamaguchi Tetsuya , Yamamoto Noboru , Kunitoh Hideo , Tamura Tomohide , Yamada Yasuhide , Ohe Yuichiro , Yoshida Teruhiko , Minami Hironobu , Ohtsu Atsushi , Matsumura Yasuhiro , Saijo Nagahiro , Okuda Haruhiro
Published: April 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Association of UDP‐glucuronosyltransferase 1A1 (UGT1A1) genetic polymorphisms *6 and *28 with reduced clearance of SN‐38 and severe neutropenia in irinotecan therapy was demonstrated in Japanese cancer patients.

• The detailed gene structure of CES1 has been characterized.

• Possible functional SNPs in the promoter region have been reported.

WHAT THIS STUDY ADDS

• Association of functional CES1 gene number with AUC ratio [(SN‐38 + SN‐38G)/irinotecan], an in vivo index of CES activity, was observed in patients with irinotecan monotherapy.

• No significant effects of major CES1 SNPs on irinotecan PK were detected.

AIMS

Human carboxylesterase 1 (CES1) hydrolyzes irinotecan to produce an active metabolite SN‐38 in the liver. The human CES1 gene family consists of two functional genes, CES1A1 (1A1) and CES1A2 (1A2), which are located tail‐to‐tail on chromosome 16q13‐q22.1 (CES1A2‐1A1). The pseudogene CES1A3 (1A3) and a chimeric CES1A1 variant (var1A1) are also found as polymorphic isoforms of 1A2 and 1A1, respectively. In this study, roles of CES1 genotypes and major SNPs in irinotecan pharmacokinetics were investigated in Japanese cancer patients.

METHODS

CES1A diplotypes [combinations of haplotypes A (1A3‐1A1), B (1A2‐1A1), C (1A3‐var1A1) and D (1A2‐var1A1)] and the major SNPs (−75T>G and −30G>A in 1A1, and −816A>C in 1A2 and 1A3) were determined in 177 Japanese cancer patients. Associations of CES1 genotypes, number of functional CES1 genes (1A1, 1A2 and var1A1) and major SNPs, with the AUC ratio of (SN‐38 + SN‐38G)/irinotecan, a parameter of in vivo CES activity, were analyzed for 58 patients treated with irinotecan monotherapy.

RESULTS

The median AUC ratio of patients having three or four functional CES1 genes (diplotypes A/B, A/D or B/C, C/D, B/B and B/D; n= 35) was 1.24‐fold of that in patients with two functional CES1 genes (diplotypes A/A, A/C and C/C; n= 23) [median (25th–75th percentiles): 0.31 (0.25–0.38) vs. 0.25 (0.20–0.32), P= 0.0134]. No significant effects of var1A1 and the major SNPs examined were observed.

CONCLUSION

This study suggests a gene‐dose effect of functional CES1A genes on SN‐38 formation in irinotecan‐treated Japanese cancer patients.
Risk factors for venous thrombosis – current understanding from an epidemiological point of view
Authors: Lijfering Willem M. , Rosendaal Frits R. , Cannegieter Suzanne C.
Published: April 2010

Epidemiological research throughout the last 50 years has provided the long list of risk factors for venous thrombosis that are known today. Although this has advanced our current understanding about the aetiology of thrombosis, it does not give us all the answers: many people have several of these risk factors but never develop thrombosis; others suffer from thrombosis but have none. In this review, we discuss how risk factors for venous thrombosis can be interpreted with use of several epidemiological models. We comment on how to explain why risk factors for first venous thrombosis differ from recurrent venous thrombosis, and use a causal model to better understand risk of first and recurrent venous thrombosis.
Natural killer T cells are dispensable in the development of allergen-induced airway hyperresponsiveness, inflammation and remodelling in a mouse model of chronic asthma
Authors: Koh Y-I , Shim J-U , Lee J-H , Chung I-J , Min J-J , Rhee J H , Lee H C , Chung D H , Wi J-O
Published: April 2010

Natural killer T (NK T) cells have been shown to play an essential role in the development of allergen-induced airway hyperresponsiveness (AHR) and/or airway inflammation in mouse models of acute asthma. Recently, NK T cells have been reported to be required for the development of AHR in a virus induced chronic asthma model. We investigated whether NK T cells were required for the development of allergen-induced AHR, airway inflammation and airway remodelling in a mouse model of chronic asthma. CD1d−/− mice that lack NK T cells were used for the experiments. In the chronic model, AHR, eosinophilic inflammation, remodelling characteristics including mucus metaplasia, subepithelial fibrosis and increased mass of the airway smooth muscle, T helper type 2 (Th2) immune response and immunoglobulin (Ig)E production were equally increased in both CD1d−/− mice and wild-type mice. However, in the acute model, AHR, eosinophilic inflammation, Th2 immune response and IgE production were significantly decreased in the CD1d−/− mice compared to wild-type. CD1d-dependent NK T cells may not be required for the development of allergen-induced AHR, eosinophilic airway inflammation and airway remodelling in chronic asthma model, although they play a role in the development of AHR and eosinophilic inflammation in acute asthma model.
The effect of adrenomedullin and cold stress on interleukin-6 levels in some rat tissues
Authors: Yildirim N C , Yurekli M
Published: April 2010

Stress known to stimulate sympathetic activity, as well as the hypothalamic–pituitary–adrenal axis (HPA), produces a significant increase in adrenomedullin (AdM) levels, suggesting a regulatory or protective role for AdM in countering HPA activation that follows a variety of stressors. Stressors can modulate the secretion of proinflammatory cytokines. Interleukin (IL)-6 is a potent activator of the HPA and appears to play a pathogenic role in conditions related to stress. In the present study, we investigated the administration of AdM on IL-6 levels in cold exposed rats. Male Wistar rats were divided into four groups as control, adrenomedullin treatment, cold stress and cold stress+adrenomedullin-treated groups. In the adrenomedullin-treated group, animals received intraperitoneal (i.p.) injection of adrenomedullin (2000 ng/kg body weight) once a day for a week. For the cold stress exposure the rats were kept in separate cages at 10°C for a week. Control group rats were kept in laboratory conditions. The concentration of IL-6 was determined using an enzyme-linked immunosorbent assay (ELISA) kit. When compared to control, IL-6 levels increased significantly in the cold stress- and adrenomedullin-treated groups (P < 0·05). Administration of AdM in addition to cold stress decreased IL-6 levels in lung and liver, but increased in brain and heart when compared to control (P < 0·05). The results suggest that cold stress may induce increase of rat proinflammatory cytokine IL-6 and adrenomedullin may play a regulatory or protective role for cold stress.
Allogeneic mesenchymal stem cells do not protect NZB × NZW F1 mice from developing lupus disease
Authors: Youd M , Blickarz C , Woodworth L , Touzjian T , Edling A , Tedstone J , Ruzek M , Tubo R , Kaplan J , Lodie T
Published: April 2010

Mesenchymal stem cell (MSC) therapy has shown promise clinically in graft-versus-host disease and in preclinical animal models of T helper type 1 (Th1)-driven autoimmune diseases, but whether MSCs can be used to treat autoimmune disease in general is unclear. Here, the therapeutic potential of MSCs was tested in the New Zealand black (NZB) × New Zealand white (NZW) F1 (NZB/W) lupus mouse model. The pathogenesis of systemic lupus erythematosus involves abnormal B and T cell activation leading to autoantibody formation. To test whether the immunomodulatory activity of MSCs would inhibit the development of autoimmune responses and provide a therapeutic benefit, NZB/W mice were treated with Balb/c-derived allogeneic MSCs starting before or after disease onset. Systemic MSC administration worsened disease and enhanced anti-double-stranded DNA (dsDNA) autoantibody production. The increase in autoantibody titres was accompanied by an increase in plasma cells in the bone marrow, an increase in glomerular immune complex deposition, more severe kidney pathology, and greater proteinuria. Co-culturing MSCs with plasma cells purified from NZB/W mice led to an increase in immunoglobulin G antibody production, suggesting that MSCs might be augmenting plasma cell survival and function in MSC-treated animals. Our results suggest that MSC therapy may not be beneficial in Th2-type T cell- and B cell-driven diseases such as lupus and highlight the need to understand further the appropriate application of MSC therapy.
Phenological shifts of three interacting zooplankton groups in relation to climate change
Authors: SCHLÜTER MERJA H. , MERICO AGOSTINO , REGINATTO MARCEL , BOERSMA MAARTEN , WILTSHIRE KAREN H. , GREVE WULF
Published: April 2010

Over the past several decades, global warming has been linked to shifts in the distributions and abundances of species. In the southern North Sea, temperatures have increased in the last three decades and this will likely have consequences on the seasonality of marine organisms living in the area. Ctenophores such as Beroe gracilis and Pleurobrachia pileus could be particularly affected by changes in their own phenology and that of their prey, thus causing shifts in ecosystem function. Despite their global relevance and their potentially deleterious effect on the fishing industry, only a few long‐term records of ctenophore abundance exist, and most of these records are semiquantitative in nature. Therefore, our knowledge of the influence of environmental factors on their population development is presently very limited. In this study, the long‐term abundance dynamics of B. gracilis, P. pileus and their food calanoid copepods were analysed for a highly temporally resolved time series in the German Bight at Helgoland Roads. Special attention was focused on the response of these organisms to climate warming. Bayesian statistics showed that the phenology of the two ctenophores shifted in a step‐like mode in the year 1987/1988 to permanent earlier appearances. The seasonal change in the population blooms of P. pileus and B. gracilis correlated remarkably well with a step‐like increase in winter and spring sea surface temperatures of the southern North Sea. Possible explanations for the changes observed in these organisms include higher reproductive rates, increased winter survival rates or both. Interannual variations in ctenophore abundances correlated best with the interannual changes in spring temperatures, although the impact of temperature on B. gracilis appeared less pronounced. The changes in copepods abundance were not consistent with changes in P. pileus and B. gracilis. P. pileus showed longer periods of high abundance after the permanent seasonal advancement. These longer periods were correlated with a decline in the average autumn abundance of copepods. Changes in the phenology of these organisms raise the concerns on the declining state of fish stocks, which could potentially be exacerbated by gelatinous zooplankton outbreaks. These conditions may ultimately lead to trophic dead ends by channelling the flow of energy away from higher trophic levels.