bluuebunny/crossref_metadata_2025 huggingface dataset:
Particle Holdup Profiles in Horizontal Gas‐liquid‐solid Multiphase Flow Pipeline
Authors: Bello O. O. , Reinicke K. M. , Teodoriu C.
Published: November 2005

Sand holdup is one of the most important hydrodynamic parameters that is needed for performance estimation, design, operation and control of oil‐gas‐sand multiphase production and pipeline transportation systems. The performance of oil‐gas‐sand multiphase flow can be reliably evaluated by measuring the sand holdup in such oil‐gas‐sand multiphase production and pipeline transportation systems. In the present work, a local sand holdup has been measured under conditions analogous to the horizontal oil‐gas‐sand three‐phase slug flow in pipelines. Accurate local sand particle holdup measurements were performed by the digital imaging technique. The results revealed the influence of operating conditions such as gas and liquid velocities and sand particle loading on the distribution of the local sand particle holdup in the horizontal air‐water‐sand multiphase slug flow pipe. Explanations for the observed trends are provided, shedding light on the general structures and mechanisms of the distribution of the local sand holdup in a horizontal oil‐gas‐sand three‐phase slug flow. Such information on the horizontal air‐water‐sand three‐phase slug flow mechanisms are essential to advance the mechanistic approach for predicting local sand holdup distribution and the subsequent effect on sand deposition during multiphase petroleum production and transfer operations.
Catalytic Dehydration of 1,2‐Butanediol to n‐Butyraldehyde in Sub‐ and Supercritical Water
Authors: Ott L. , Kohl S. , Bicker M. , Vogel H.
Published: November 2005

The change of the raw material basis to alternative sources, especially biomass, is advisable because of both the continuous shortage of fossile resources and the advancing change in world climate. Carbohydrates have the highest share in biomass. However, as they are overfunctionalized with chemically almost equal hydroxy groups, the high‐scale industrial use of carbohydrates is restrained. In addition, the diversity and the high amount of functional groups of carbohydrates complicate the prediction of possible reaction pathways. This is the reason why monoalcohols and polyols are used as model compounds. One interesting reaction is the dehydration of 1,2‐butanediol to n‐butyraldehyde, an important chemical intermediate. Supercritical water is an appropriate reaction medium for dehydrations because of its special physical and chemical properties. The addition of acids enhances the reaction rate but at the same time intensifies corrosion. Sulfate salts, especially zinc sulfate, can have similar positive effects without increasing the corrosion potential. The experimental results of the catalytic influence of different metal sulfate salts on the dehydration of 1,2‐butanediol to n‐butyraldehyde are presented in this paper.
Evaluative Approach for Process Development
Authors: Cziner K. , Virkki‐Hatakka T. , Hurme M. , Turunen I.
Published: November 2005

A novel method for process development is presented. The approach is based on the evaluation of available technologies and aiming at new and innovative designs by combining their best features in a creative way. The knowledge is extracted either directly from similar processes or from processes with sufficient analogy. A case study on melamine process development is given to illustrate the application of the methodology.
Separation of Toluene and n‐Heptane through Emulsion Liquid Membranes Containing Ag+ as Carrier
Authors: Chakraborty M. , Bart H.‐J.
Published: November 2005

Using silver ions as carrier in oil/water/oil‐type emulsion liquid membranes, batch wise extraction experiments were carried out to separate toluene from a mixture of toluene and n‐heptane. The separation performances, represented by the permeation rate, emulsion stability, and separation factor, were analyzed systematically by varying the operating parameters, viz., contact time, concentration of Ag+, emulsification time, surfactant concentration, membrane stabilizer concentration, relative amount of solvent, and initial feed phase concentration. The emulsion liquid membranes thus formed are stable, and Ag+ and surfactant concentrations strongly affect the permeation behavior of toluene.
Development of a Ceramic Micro Heat Exchanger – Design, Construction, and Testing
Authors: Alm B. , Knitter R. , Haußelt J.
Published: November 2005

This article presents the development of a ceramic micro heat exchanger. Starting from its geometrical design, results obtained from a simplified simulation of the heat exchanger efficiency will be given. The alumina microcomponents were manufactured by a rapid prototyping process chain. Here, stereolithography was combined with a low‐pressure injection molding process for the rapid and precise manufacturing of ceramic components down to the micrometer range. A micro heat exchanger, joined from sintered components using a glass solder, was applied as a prototype and checked for its performance at a system pressure of 8 bar.
Effects of chemoattractant pteridines upon speed of D. discoideum vegetative amoebae
Authors: Rifkin Jared L. , Goldberg Robert R.
Published: November 2005

Movements of D. discoideum vegetative amoebae responding to pteridine chemoattractants, folate acid and pterin, were recorded. A vector analysis of these images was performed to partition the speed and orientation components of these motility patterns. This study demonstrates that in addition to orientation (chemotaxis), stimulated speed (chemokinesis) is an important component of the directed migration of these amoebae. Furthermore, the primary difference in their response to folate versus pterin is in speed rather than orientation. The data support a model of directed migration of these cells in which there are (1) separate signal translation pathways consequent from folate versus pterin reception and (2) specific pathways leading to increase in orientation versus speed. Cell Motil. Cytoskeleton, 2006. © 2005 Wiley‐Liss, Inc.
Src‐dependent phosphorylation of Scar1 promotes its association with the Arp2/3 complex
Authors: Ardern Hazel , Sandilands Emma , Machesky Laura M. , Timpson Paul , Frame Margaret C. , Brunton Valerie G.
Published: November 2005

The WAVE/Scar proteins regulate actin polymerisation at the leading edge of motile cells via activation of the Arp2/3 complex in response to extracellular cues. Within cells they form part of a pentameric complex that is thought to regulate their ability to interact and activate the Arp2/3 complex. However, the exact mechanism for this is not known. We set out to assess whether phosphorylation of Scar1 by the non‐receptor tyrosine kinase Src may influence the function of Scar1 and its ability to regulate Arp2/3‐mediated actin polymerisation. We show that Scar1 is phosphorylated by Src in vitro and in vivo and identify tyrosine 125 as the major site in Scar1 to be phosphorylated in cells. Src‐dependent phosphorylation of Scar1 on tyrosine 125 enhances its ability to bind to the Arp2/3 complex and regulates its ability to control actin polymerisation in cells. Thus, Src may act as an intermediary to regulate the activity of the Arp2/3 complex in response to external stimuli, via modulation of its interaction with WAVE/Scar proteins. Cell Motil. Cytoskeleton, 2006. © 2005 Wiley‐Liss, Inc.
Caenorhabditis elegans expresses three functional profilins in a tissue‐specific manner
Authors: Polet D. , Lambrechts A. , Ono K. , Mah A. , Peelman F. , Vandekerckhove J. , Baillie D. L. , Ampe C. , Ono S.
Published: November 2005

Profilins are actin binding proteins, which also interact with polyphosphoinositides and proline‐rich ligands. On the basis of the genome sequence, three diverse profilin homologues (PFN) are predicted to exist in Caenorhabditis elegans. We show that all three isoforms PFN‐1, PFN‐2, and PFN‐3 are expressed in vivo and biochemical studies indicate they bind actin and influence actin dynamics in a similar manner. In addition, they bind poly(L‐proline) and phosphatidylinositol 4,5‐bisphosphate micelles. PFN‐1 is essential whereas PFN‐2 and PFN‐3 are nonessential. Immunostainings revealed different expression patterns for the profilin isoforms. In embryos, PFN‐1 localizes in the cytoplasm and to the cell–cell contacts at the early stages, and in the nerve ring during later stages. During late embryogenesis, expression of PFN‐3 was specifically detected in body wall muscle cells. In adult worms, PFN‐1 is expressed in the neurons, the vulva, and the somatic gonad, PFN‐2 in the intestinal wall, the spermatheca, and the pharynx, and PFN‐3 localizes in a striking dot‐like fashion in body wall muscle. Thus the model organism Caenorhabditis elegans expresses three profilin isoforms and is the first invertebrate animal with tissue‐specific profilin expression. Cell Motil. Cytoskeleton, 2006.© 2005 Wiley‐Liss, Inc.
Mesp1‐nonexpressing cells contribute to the ventricular cardiac conduction system
Authors: Kitajima Satoshi , Miyagawa‐Tomita Sachiko , Inoue Tohru , Kanno Jun , Saga Yumiko
Published: November 2005

Previous fate mapping analysis, using Cre recombinase driven by the Mesp1 locus, revealed that Mesp1 is expressed in almost all of the precursors of the cardiovascular system, including the endothelium, endocardium, myocardium, and epicardium. Mesp1‐nonexpressing cells were found to be restricted to the outflow tract cushion and along the interventricular septum (IVS), which is a location that is suggestive of specialized cardiac conduction system (CCS). In our current study, we examined the identity of these IVS cells by using the pattern of β‐galactosidase activity in CCS‐lacZ mice. In addition, by crossing Mesp1‐Cre and floxed GFP reporter mice with CCS‐lacZ mice, we have calculated that approximately 20% of the ventricular CCS within the IVS corresponds to Mesp1‐nonexpressing cells. These data suggest that the ventricular CCS is of heterocellular origin. Furthermore, we indicate a possibility that a population of the cells that contribute to the ventricular CCS might be distinguished at an early stage of development. Developmental Dynamics 235:395–402, 2006. © 2005 Wiley‐Liss, Inc.
Lysophosphatidic acid cooperates with EGF in inducing branching morphogenesis of embryonic mouse salivary epithelium
Authors: Noguchi Yohei , Okamoto Atsushi , Kasama Takeshi , Imajoh‐Ohmi Shinobu , Karatsu Takashi , Nogawa Hiroyuki
Published: November 2005

Epithelial morphogenesis is supported by diffusible growth factors and by nondiffusible cell substrata, such as laminin and fibronectin. When embedded in a laminin‐rich basement‐membrane substratum, embryonic mouse submandibular epithelium undergoes cell proliferation and branching morphogenesis in response to epidermal growth factor (EGF) in mesenchyme‐free culture but not in serum‐free medium. In this study, we sought to identify the biologically active factor in serum. As this factor was heat‐stable and trypsin‐resistant, the lipid fraction was analyzed. Horse serum was fractionated by ethanol extraction, Folch partition with chloroform–methanol–water, and high‐performance liquid chromatography, and we tested the branch‐inducing activity of each fraction. We also analyzed the partially purified fraction with a mass spectrometer, indicating that the active fraction largely consisted of lysophosphatidyl‐hexose. Finally we identified the molecule as lysophosphatidic acid (LPA), because, whereas lysophosphatidyl‐inositol had only a slight branch‐inducing activity, its relevant LPA fully substituted for serum and induced branching morphogenesis in cooperation with EGF. LPA receptor genes were expressed in submandibular epithelial cells. DNA‐synthesizing cells were abundant only when cultured in the presence of both EGF and LPA, but not either singly. Developmental Dynamics 235:403–410, 2006. © 2005 Wiley‐Liss, Inc.
Assessment of land‐use impact on streamflow via a grid‐based modelling approach including paddy fields
Authors: Kim Seong Joon , Kwon Hyung Joong , Park Geun Ae , Lee Mi Seon
Published: November 2005

To investigate the hydrologic impacts of land‐use changes on streamflow for an urbanizing watershed with paddy fields, a grid‐based daily hydrologic model was adopted. The model was calibrated with two years (2000–2001) of observed streamflow data and validated using 5 months (2001) of measured soil moisture data and 1 year (2002) of observed streamflow data. After the model was tested, it was run to estimate impacts of urbanization on each hydrologic component with the land‐use data sets for 1986, 1994, and 2002 generated from Landsat TM satellite images. Total runoff increased from 41·4% (1986) to 44·9% (2002) for a 5·4% increase in urban area, implying that direct runoff increase exceeded baseflow decrease. Urbanization affected the proportions of direct runoff for each land‐use category more than the change in total runoff and the ratio of direct runoff to total runoff. The change proportions in direct runoff for urban areas, paddy fields, and forest were 14·3%, −9·8% and −6·7% respectively for a 5·4% increase, 4·6% decrease and 3·4% decrease in each land‐use area respectively. The results indicate that paddy fields play an important role in runoff regulation, and the evaluation method can assist regional policy makers in developing land management strategies that minimize hydrologic impacts on streamflow. Copyright © 2005 John Wiley & Sons, Ltd.
Estimation of rating‐curve parameters for sedimentation using a physical model
Authors: Kazama So , Suzuki Kenji , Sawamoto Masaki
Published: November 2005

Parameters in the lumped sedimentation formula rating curve Qs = KQP are discussed to estimate sedimentation in a basin without calibration in that basin. We were unable to determine the physical meaning of the parameters that are widely used by many researchers. A physically based sediment equation, the Itakura–Kishi equation, prepares a numerical experiment system to discuss rating‐curve parameter characteristics. Experimental results suggest a method to estimate K and P parameters from geomorphologic data, particle diameter, riverbed slope, and roughness by changing experimental conditions. The results yield P from the particle diameter and riverbed gradient, and K from the exponential function of the gradient, particle diameter and roughness. Both the proposed rating curve and the Itakura–Kishi methods are applied to the Mekong River basin combining with the BTOP‐MC (block‐wise TOP model with Muskingum–Cunge routing) model, a distributed hydrologic model, to discuss estimations and their characteristics in practical fields. The proposed methods for K and P provide good agreement with mainstream data from the Mekong River under conditions of gradual water‐level variation. Copyright © 2005 John Wiley & Sons, Ltd.
Forest categorization according to dry‐canopy evaporation rates in the growing season: comparison of the Priestley–Taylor coefficient values from various observation sites
Authors: Komatsu Hikaru
Published: November 2005

Summarizing observed dry‐canopy evaporation (hereafter, evaporation) data from earlier papers, we developed a scheme for forest categorization according to evaporation rates in the growing season. Evaporation rates were represented by the Priestley–Taylor coefficient α calculated for daytime. We examined relationships between forest properties (e.g. climatic regions, leaf types) and α values. We obtained α data for 67 forest sites from earlier papers. Based on these data, we found (i) a clear difference in α values between broad‐leaved and coniferous forests, (ii) a greater variation in α values between individual coniferous forests than between individual broad‐leaved forests, and (iii) a clear relationship between canopy height and α values for coniferous forests. These three results were supported by surface conductance data summarized from earlier papers. We concluded that forests should be primarily classified into broad‐leaved and coniferous forests, and that coniferous forests should be further classified according to canopy height. This classification scheme is applicable only to forests with projected leaf area index (LAI) ≥3·0. Regardless of this LAI limitation, this classification will be useful because many forests satisfy this LAI limitation.

This paper shows valuable results in the following two respects. First, this paper explicitly shows the difference in evaporation rates between broad‐leaved and coniferous forests. Although this difference would have been implicitly recognized, this difference has not been shown based on adequate amounts of observed data. Second, it is shown that classifying coniferous forests according to canopy height is as important as classifying forests according to leaf type (broad‐leaved or coniferous). Although studies have recognized the effect of canopy height on evaporation rates, the significant effect of canopy height on evaporation rates, compared with the effects of other factors on evaporation rates, has not previously been shown. Copyright © 2005 John Wiley & Sons, Ltd.
Observations and modelling of seawater intrusion for a small limestone island aquifer
Authors: Momii K. , Shoji J. , Nakagawa K.
Published: November 2005

Seawater intrusion in coastal aquifers is a widespread and serious problem in many parts of the world. Groundwater degradation due to seawater intrusion is often accentuated in small island aquifers due to overpumping or limited replenishing amounts of precipitation. Seawater intrusion and groundwater dynamics in a small limestone aquifer on Yoron Island, Japan, were investigated. Observations in the field were compared with results of a numerical model based on the sharp interface approach coupled with a tank model in order to take into account groundwater recharge and evapotranspiration. The field observations indicated that the sinusoidal fluctuations of groundwater level near the coastline occur in response to diurnal tides. The tidal fluctuations are damped, however, at a distance of 1 km from the coastline and the seasonal variation of groundwater level is small. The transition zone between freshwater and seawater in the inland coral limestone layer is narrow relative to the aquifer thickness, and the estimated interface by the Ghyben–Herzberg relation does not always represent the location of the transition zone for unsteady conditions. Suitable site‐specific parameters used in the tank model, as well as effective porosity and hydraulic conductivity of the groundwater aquifer, are discussed, and observed and modelled groundwater level fluctuations are compared for the study site. It is shown that calculated groundwater levels and location of seawater intrusion by the coupled numerical model are in relatively good agreement with observed results. Copyright © 2005 John Wiley & Sons, Ltd.
Incorporation of a nanosplitter interface into an LC‐MS‐RD system to facilitate drug metabolism studies
Authors: Andrews Christine L. , Li Feng , Yang Eric , Yu Chung‐Ping , Vouros Paul
Published: November 2005

In the work reported here, a novel interface, the nanosplitter, is incorporated into the drug metabolism laboratory in order to enhance the analytical capabilities of detecting and identifying drug‐related metabolites to support drug metabolism studies during the drug development process. When an existing LC‐MS‐radiometric detector (RD) system is coupled with this nanosplitter, the system becomes capable of performing dynamic microspray under a typical analytical LC method. With the superior MS sensitivity offered by this system, most of the analytical LC methods developed for metabolite profiling can then be easily adopted for metabolite identification work. The improvement of these analytical capabilities can streamline the entire process of the drug metabolism study. In the experiments presented here, the nanosplitter interface coupled with analytical HPLC systems (e.g. 4.6 × 250 mm column @ 1 ml/min) demonstrated significant increases in MS signal (2× to 40× peak area) when compared to the standard LC‐MS interface for both in vitro and in vivo metabolism studies. Furthermore, this signal gain facilitated the MS detection of additional metabolites (observed in the radiometric trace) that were below the MS level of detection when using the standard interface. Copyright © 2005 John Wiley & Sons, Ltd.
Location and base selectivity on fragmentation of brominated oligodeoxynucleotides
Authors: Buré Corinne , Castaing Bertrand , Lange Catherine , Delmas Agnès F.
Published: November 2005

Bromine‐modified oligodeoxynucleotides (ODNs) were fragmented in the electrospray source to study the influence of brominated bases on fragmentation. Several 13‐mer ODNs containing a brominated pyrimidine base, BrdU (5‐bromodeoxyuridine) or BrdC (5‐bromodeoxycytidine), were analyzed. Low cone voltage fragmentation yields a loss of the brominated base with a preferential loss for the brominated base closer to the 5′‐end (2‐position > 4‐position > 12‐position) as well as a preferential loss of BrdU over BrdC. Higher cone voltage produces backbone fragmentation with complementary an‐base and wm ions close to the brominated base. On the basis of these observations, we located the brominated base in the sequence for all of the ODNs studied. Copyright © 2005 John Wiley & Sons, Ltd.
Diastereoselective fragmentation of chiral α‐aminophosphonic acids/metal ion aggregates
Authors: Filippi Antonello , Speranza Maurizio , Paladini Alessandra , De Carolis Roberta , Guidoni Anna Giardini , Laganà Aldo , Satta Mauro
Published: November 2005

Diastereomeric clusters of general formula [MAB2]+ and [MA2B]+ (M = Li(I), Na(I), Ag(I), Ni(II)‐H, or Cu(II)‐H; A = (R)‐(−)‐ and (S)‐(+)‐(1‐aminopropyl)phosphonic acid; B = (1R)‐(−)‐ and (1S)‐(+)‐(1‐aminohexyl)phosphonic acid) have been readily generated in the electrospray ionization (ESI) source of a triple‐quadrupole mass spectrometer and their collision‐induced dissociation (CID) investigated. CID of diastereomeric complexes, e.g. [MAS(BS)2]+ and [MAR(BS)2]+, leads to fragmentation patterns characterized by Rhomo = [MASBS]+/[M(BS)2]+ and Rhetero = [MARBS]+/[M(BS)2]+ abundance ratios, which depend upon the relative stability of the diastereomeric [MASBS]+ and [MARBS]+ complexes in the gas phase. The chiral resolution factor Rchiral = Rhomo/Rhetero is found to depend not only on the nature of the M ion but also on that of the fragmenting species, whether [MAB2]+ or [MA2B]+. The origin of this behavior is discussed. Copyright © 2005 John Wiley & Sons, Ltd.
Creative marketing strategies in small museums: up close and innovative
Authors: McNichol Theresa
Published: November 2005

Museums are seeing decreasing resources along with increasing competition (such as the entertainment industry's recent foray into the education arena) for their market share (TiLE, Oct 2002). The prevalent perception that nonprofit institutions as a sector are mismanaged also requires museums to become more businesslike in their management and their marketing (Kotler & Kotler, 1998; Andreasen & Kotler, 2002; Salamon, 2003). Although larger museums have more access to human and economic capital, this article demonstrates how the flexibility and agility of smaller institutions positions them well to leverage their resources with creativity and innovation. To give credibility to the museum examples, the discussion recounts how the American wine industry rose in prominence both at home and abroad by sidestepping traditional marketing research methods, using instead an approach that was more like art.

Copyright © 2005 John Wiley & Sons, Ltd.
The marketing/creativity interface: a case study of a visual artist
Authors: O'Reilly Daragh
Published: November 2005

This paper aims to contribute to an understanding of the marketing/creativity interface in the visual arts at the level of the individual artist. Proceeding, broadly speaking, from a constructivist perspective and using a qualitative case study approach, it examines a visual artist's personal construction of her creative and business work. The analysis highlights the significance of emotional, cognitive, spiritual and physical processes for the artist's positioning, process, and products, as well as her difficulties with promotion and pricing issues. It was seen, following Fillis (2004), that, at the level of an individual artist, her work may be not only product‐oriented but self‐oriented. It therefore behoves artists and their agents to be able to offer appropriately distinguishing promotional accounts of the artist's artistic identity, process and work based on a deep self‐reflexive awareness and understanding by the artist of her own creative practice.

Copyright © 2005 John Wiley & Sons, Ltd.
Creativity, job performance and their correlates: a comparison between nonprofit and profit‐driven organizations
Authors: Suh Taewon , Shin Hochang
Published: November 2005

This study explores a research model concerning creativity, job performance, and their correlates in the nonprofit organization setting. The findings of this study suggest that a set of differences in the areas of creativity, job performance, and their correlates exists between the marketers in nonprofit organizations and the marketers in profit‐driven organizations. These findings reveal the need for contingency theories in this area, with emphasis centered on environmental differences. It is hoped that this study will draw the attention of many researchers toward topics concerning organizational creativity in the nonprofit organization setting.

Copyright © 2005 John Wiley & Sons, Ltd.
Effect of immobilization with chondroitin‐6‐sulfate and grafting with chitosan on fibroblast and antibacterial activity of polyester fibers
Authors: Jou Chi‐Hsiung , Lee Jui‐Sheng , Chou Wen‐Li , Yu Da‐Guang , Yang Ming‐Chien
Published: November 2005

Poly(ethylene terephthalate) (PET) fibers were treated with 60Co‐γ‐ray and grafted with acrylic acid (AA), and further grafted with chitosan (CS) via esterification. Afterwards these CS‐grafted fibers were then immobilized with chondroitin‐6‐sulfate (ChS). The blood compatibility of PET was reduced by grafting with CS, while improved by immobilizing with ChS. The antibacterial activity of CS against Staphylococcus aureus, and Pseudomonas aeruginosa was retained after ChS‐immobilization. After immobilizing ChS, the L929 fibroblasts cell proliferation was higher than CS‐grafting PET fibers. The results indicate that by grafting with CS and immobilizing with ChS, PET fibers can not only exhibit antibacterial activity, but also improve the cell proliferation for fibroblast activity. Copyright © 2005 John Wiley & Sons, Ltd.
Results of a phase II trial testing interferon‐alpha 2b and cytarabine in children and adolescents with chronic myelogenous leukemia
Authors: Millot Frédéric , Guilhot Joelle , Nelken Brigitte , Leblanc Thierry , Leverger Guy , Bernard Frédéric , Gandemer Virginie , Béhard Catherine , Berger Claire , Cornu Guy , Duchène Sylvain , Guilhot François
Published: November 2005

Background

Chronic myelogenous leukemia (CML) is a rare disease in children and only few data are available concerning the results of interferon based therapy in this age group. Before the imatinib mesylate era, a prospective phase II trial was conducted to assess the efficacy and tolerance of a combination of interferon‐alpha 2b (IFN) and cytarabine in children with CML in first chronic phase without a suitable HLA‐identical donor.

Procedure

Fourteen consecutive children were recruited from 12 pediatric centers. Children received daily IFN (5 million U/m2) and subcutaneous cytarabine (20 mg/m2) for 10 days every month.

Results

The median duration of follow‐up is 13 months (range 2–32 months). Seven children achieved a complete hematologic response after a median time of treatment of 3 months (range 1 week–4 months). Three children were not evaluable for the cytogenetic response. A major cytogenetic response was achieved in seven patients (including complete cytogenetic response in two patient) within 12 months. The median time to major cytogenetic response was 7 months (range 3–12 months). Thirteen patients discontinued the treatment protocol after a median time of 11 months. Probability of progression free survival at 11 months was 83% (95% CI, 61%–100%). Grade 3 and 4 toxicity was observed in eight patients. The most frequently reported drug‐related events were fever, mucositis, neutropenia, and thrombocytopenia.

Conclusions

The combination of IFN and cytarabine provides hematologic and cytogenetic responses in children and adolescents with CML. In the imatinib mesylate era, the role of this combination as second line therapy in children with CML remains to be determined. Pediatr Blood Cancer 2006; 47:555–559. © 2005 Wiley‐Liss, Inc.
Improving clinical care and elucidating the pathophysiology of Diamond Blackfan anemia: An update from the Diamond Blackfan Anemia Registry
Authors: Lipton Jeffrey M. , Atsidaftos Eva , Zyskind Israel , Vlachos Adrianna
Published: November 2005

Diamond Blackfan anemia (DBA) is a heterogeneous genetic disorder characterized by red cell aplasia, congenital anomalies, and a predisposition to cancer. Although incompletely understood, the erythroid failure in DBA appears to result from the accelerated apoptosis of affected erythroid progenitors/precursors. One of what appears to be multiple DBA genes, coding for a ribosomal protein RPS 19, has been cloned. Even within multiplex families individuals may vary dramatically as to the degree of anemia, response to treatment and the presence of congenital anomalies. The Diamond Blackfan Anemia Registry (DBAR), a comprehensive database of pediatric and adult patients with DBA who are enrolled after informed consent, was designed to overcome two significant obstacles encountered in the study of a rare disease; the reporting bias inherent in the literature and the lack of an active patient database. To enroll, patients, their families and their physicians complete a detailed questionnaire. A review of medical records and telephone interviews are performed to complete and clarify the information provided. As of May 1, 2005, 420 patients have been enrolled in the DBAR. Epidemiological, clinical, and laboratory data have been collected and analyzed. The DBAR has provided new information on the clinical presentation, outcome and genetics of DBA as well as a better description of congenital malformations and cancer predisposition. This has resulted both in improved clinical care of patients with DBA as well as providing new insights into the pathophysiology of this complex disorder. © 2005 Wiley‐Liss, Inc.
The effectiveness of a peer support camp for siblings of children with cancer
Authors: Sidhu Ranita , Passmore Anne , Baker David
Published: November 2005

Background

Siblings of children with cancer have higher levels of psychological stress and adaptational difficulties compared to siblings of healthy children and children with other chronic illness. This is the first study to report on the mental health of Australian siblings of children with cancer and examines the effects of a therapeutic peer support camp—Camp Onwards, as an intervention.

Procedure

A protocol, designed to reduce levels of distress, improve social competence, and improve knowledge about the impact of cancer and its treatment was developed. Siblings (n = 26) 8–13 years were assessed using standardised self‐report measures pre and post intervention and at −8 weeks follow‐up with: the Behaviour Assessment for Children (BASC) (Reynolds & Kamphaus, 1992), Self Perception Profile for Children (SPP‐C) (Harter, 1985), Sibling Perception Questionnaire (SPQ) (Carpenter & Sahler, 1991).

Results

Change was measured using paired t tests. At pre‐test, 40% of the sample demonstrated increased levels of emotional distress when compared to the normal population. Post intervention, siblings reported lower levels of distress demonstrated by decreased anxiety (P = 0.01) and positive changes in the Self Report of Personality [BASC] (P = 0.00). Improved social competence was noted in the interpersonal domain of the SPQ (P = 0.01) and also greater social acceptance scores on the SPP‐C (P = 0.01). Improved knowledge about the impact of cancer and its treatment was evidenced by significant reductions in the fear of disease domain on the SPQ (P = 0.01).

Conclusions

Siblings who attended Camp Onwards demonstrated improved mental health outcomes that were sustained at follow‐up, demonstrating its effectiveness as an intervention strategy in supporting sibling adjustment. Pediatr Blood Cancer 2006; 47:580–588. © 2005 Wiley‐Liss, Inc.
Bone mineral density in children with sickle cell anemia
Authors: Lal Ashutosh , Fung Ellen B. , Pakbaz Zahra , Hackney‐Stephens Ekua , Vichinsky Elliott P.
Published: November 2005

Purpose

We evaluated bone mineral density (BMD) and risk factors for poor bone mineralization in children with sickle cell anemia (SCA).

Patients and Methods

Twenty‐five children with severe manifestations of SCA (frequent hospitalizations, growth delay, or need for chronic red cell transfusions) were enrolled. Bone density was assessed at lumbar spine and proximal femur with dual‐energy X‐ray absorptiometry (DXA), and Z‐scores were calculated by comparison with age, sex, and ethnicity‐specific reference data.

Results

The median age of the study population was 12.8 years (10.2–19.8 years). Calcium intake was inadequate in 60%, and serum 25‐hydroxy vitamin D (25‐OHD) level <50 nM in 74% of patients. Median Z‐scores for lumbar spine (−2.3) and proximal femur (−1.7) were markedly reduced, and 64% (95% confidence interval, 43%–82%) of patients had low bone density. Z‐scores were not related to age, growth delay, chronic transfusions, or ferritin level.

Conclusion

Our results suggest that children with severe manifestations of SCA have low BMD, and possess significant deficits in dietary calcium and circulating vitamin D. Pediatr Blood Cancer © 2005 Wiley‐Liss, Inc.
Pharmacokinetics and pharmacodynamics of intravenous epoetin alfa in children with cancer
Authors: Freeman Burgess B. , Hinds Pamela , Iacono Lisa C. , Razzouk Bassem I. , Burghen Elizabeth , Stewart Clinton F.
Published: November 2005

Background

Epoetin alfa (EPO, PROCRIT®) pharmacokinetics and pharmacodynamics were evaluated in children with malignant solid tumors receiving chemotherapy.

Procedure

Children initially received IV EPO 600 IU/kg (max dose 40,000 IU) or placebo once weekly for 16 weeks. Dose was increased to 900 IU/kg (max dose 60,000 IU) for patients not achieving a 1 g/dl increase in hemoglobin by study week 3 or 4. Serial PK samples were collected for 24 hr after the first study dose, and after the 10th or 11th dose. Serum EPO concentrations were analyzed using an ELISA assay, and pharmacokinetics were evaluated using compartmental methods.

Results

Twelve children participated; six (median age 15.2 years; range 9.3–18.6 years) were randomized to receive EPO. All children required dosage increases to 900 IU/kg due to no response. The median (range) apparent EPO AUC0–24 and clearance (CL) were 67.1 IU/ml·hr (13.8–102.6) and 0.26 L/hr/m2 (0.19–1.08), respectively. After the 10th or 11th EPO dose in four of these six EPO patients, the median (range) apparent AUC0–24 and CL of EPO was 126.5 IU/ml·hr (107.3–161.1) and 0.21 L/hr/m2 (0.15–0.25), respectively. No significant correlations were observed between pharmacokinetic parameters and pharmacodynamic effects.

Conclusions

EPO disposition in our patients was similar to other pediatric patient populations or adults receiving IV EPO. Interesting but insignificant trends were noted in pharmacodynamic effects. Pediatr Blood Cancer 2006; 47:572–579. © 2005 Wiley‐Liss, Inc.
Phase I trial of irofulven (MGI 114) in pediatric patients with solid tumors
Authors: Bomgaars Lisa R. , Megason Gail C. , Pullen Jeanette , Langevin Anne‐Marie , Dale Weitman Steve , Hershon Linda , Kuhn John G. , Bernstein Mark , Blaney Susan M.
Published: November 2005

Purpose

We performed a Phase I trial of irofulven (MGI 114) to determine the maximum tolerated dose (MTD), the dose‐limiting toxicity (DLT), and the plasma pharmacokinetics of irofulven in children ≤21 years of age with refractory/recurrent malignancies.

Experimental Design

Thirty‐five patients were entered into the study, of whom 34 were eligible. Patients received Irofulven daily × 5 days every 28 days over 10 min, following pre‐treatment with ondansetron (0.45 mg/kg) and dexamethasone (12 mg/m2). The initial dose of irofulven was 8 mg/m2 daily, with subsequent escalations to 10, 13, and 17 mg/m2. Plasma pharmacokinetic samples were obtained in a subset patients.

Results

Thirty‐two patients were assessable for toxicity, and 30 were assessable for response. In heavily pre‐treated patients, dose‐limiting thrombocytopenia was observed in two patients at the 8 mg/m2/day, and in one patient at the 6 mg/m2/day dose level. In less heavily pre‐treated patients, proteinuria and elevated creatinine were dose limiting in two patients at the 17 mg/m2/day dose level. At 13 mg/m2/day, constipation, hyperkalemia with elevated creatinine, and thrombocytopenia was dose limiting in three patients. There were no complete or partial responses. One patient with poorly differentiated carcinoma had stable disease and received 11 courses of therapy. Patients demonstrated a lower systemic exposure and greater clearance than adults treated at similar dose levels.

Conclusion

The MTD of irofulven administered daily × 5 every 28 days with concomitant ondansetron and dexamethasone is 6 mg/m2/day in heavily pre‐treated patients and 10 mg/m2/day in less heavily pre‐treated patients. © 2005 Wiley‐Liss, Inc.
Prophylactic treatment of a small child with severe factor VII deficiency using repeat dosing from a single vial of recombinant activated factor VII
Authors: Michaels Lisa A. , Philipp Claire S. , Eisele Joan , Pappas Heather , Saidi Parvin
Published: November 2005

We report our experience with a small child with severe factor VII deficiency and a history of frequent and spontaneous life‐threatening hemorrhage. The patient has received several years of successful prophylactic treatment with an every 3‐day infusion program in which she receives recombinant activated factor VII (rVIIa) using multiple doses from a single reconstituted vial over a 72‐hr period. Comparison is made to prophylactic treatment in this same patient using plasma‐derived factor VII (PDVII) using a prothrombin complex concentrate (PCC). Pediatr Blood Cancer 2007;49:736–739. © 2005 Wiley‐Liss, Inc.
An analysis of SEER data of increasing risk of secondary malignant neoplasms among long‐term survivors of childhood brain tumors
Authors: Peterson Katia M. , Shao Cheng , McCarter Robert , MacDonald Tobey J. , Byrne Julianne
Published: November 2005

Background

Advances made in treatment of a childhood brain cancer have extended the lives of many children and adolescents. Treatment success, however, brings the opportunity to assess late effects; most worrying among these are secondary malignant neoplasms (SMN). Even though the cumulative incidence is quite small, long‐term follow‐up is required because treatment‐induced cancers can occur years after initial treatment.

Procedure

The purpose of this project was to determine what treatments and what host characteristics of children treated for a primary brain cancer are associated with an increase in the risk of a SMN in long‐term survivors. Data were analyzed from 2,056 5‐year survivors, of primary brain cancer in the surveillance, epidemiology, and end results (SEER) database between 1973 and 1998. Thirty‐nine patients developed a SMN. Cox regression models were used to evaluate the independent contribution of a number of risk factors.

Results

The most important risk factor for developing a SMN in 5‐year survivors was the era in which the primary cancer was treated. Compared to treatment prior to 1979, patients treated between 1979 and 1984 had a 4.7‐fold increase in risk (P = 0.001), while those treated after 1985 had a 6.7‐fold increase in risk. (P = 0.002). Patients treated most recently carry the greatest risk of SMN development even after controlling for radiotherapy. This could be due to the increase in intensive treatment compared to earlier years.

Conclusion

Although the absolute excess risk of SMN remains quite low, continued surveillance is needed to evaluate long‐term effects of new therapies for primary brain tumors. © 2005 Wiley‐Liss, Inc.
Thymic carcinoma in a child with HIV infection
Authors: McDonald Morgan , McLean Thomas , Belhorn Thomas , Smith Scott Victor , Fordham Lynn Ansley , Woods Charles , Blatt Julie
Published: November 2005

HIV infection predisposes to cancer during childhood. In addition to the AIDS‐defining non‐Hodgkin lymphoma (NHL) and Kaposi sarcoma, a range of other lymphoid malignancies and solid tumors have been described. We report the first case of an HIV‐positive child with thymic carcinoma in the setting of regressing thymic cysts. The tumor expressed CKIT but failed to respond to imatinab mesylate after a transient response to multiagent chemotherapy. This case extends the spectrum of pediatric malignancy in the setting of HIV and suggests that patients with presumed benign thymic cysts require ongoing surveillance. Pediatr Blood Cancer 2007;49:1004–1007. © 2005 Wiley‐Liss, Inc.
Allogeneic stem cell transplantation in a patient with dyskeratosis congenita after conditioning with low‐dose cyclophosphamide and anti‐thymocyte globulin
Authors: Ayas M. , Al‐Musa A. , Al‐Jefri A. , Al‐Seraihi A. , Al‐Mahr M. , Rifai S. , El‐Solh H.
Published: November 2005

Bone marrow failure is the major cause of early mortality in patients with dyskeratosis congenita (DC); early trials with conventional conditioning regimens were associated with remarkable chronic morbidity and mortality, and the optimal conditioning regimen for these patients remains undetermined. We report a case of a child afflicted with DC who underwent related full HLA‐matched stem cell transplant (SCT) using a regimen of low dose cyclophosphamide and antithymocyte globulin (ATG). The regimen was well tolerated and associated with no significant short‐term toxicity. Pediatr Blood Cancer 2007;49:103–104. © 2005 Wiley‐Liss, Inc.
Incidence of skeletal complications during treatment of childhood acute lymphoblastic leukemia: Comparison of fracture risk with the General Practice Research Database
Authors: Högler Wolfgang , Wehl Götz , van Staa Tjeerd , Meister Bernhard , Klein‐Franke Andreas , Kropshofer Gabriele
Published: November 2005

Background

Skeletal complications during or after treatment of acute lymphoblastic leukemia (ALL) have been frequently reported and can cause substantial morbidity, yet their incidence is not well established. The present study assessed the incidence of fractures, osteonecrosis (ON), and bone pain during ALL treatment and compared the fracture incidence with age‐ and sex‐specific reference data from the UK General Practice Research Database (GPRD).

Procedure

Medical records of 122 ALL patients diagnosed at our institution from 1992 to 2004 were reviewed for information on fractures, ON, bone pain, and their anatomical location, risk group, phase of antileukemic therapy, and time since diagnosis. Evaluation of skeletal complications was followed up until July 2005 or the patient's death. Thirteen children were excluded as they were transferred to other institutions shortly after diagnosis.

Results

Skeletal complications occurred at a 5‐year incidence of 32.7%. The 5‐year incidence of fractures, ON, and isolated bone pain was 13.5%, 12.1%, and 12.3%, respectively. The relative rate of fractures adjusted for age and sex was 2.03 (95% confidence interval 1.15–3.57) compared to the GPRD, with greatest rates in children <5 years. Thirty ON occurred in 10 patients with a 15 times greater incidence in children >10 years than in those <5 years. Nearly all skeletal complications occurred during maintenance therapy at a median of 14.92 months (range 0.0–53.8) after diagnosis and in weight‐bearing bones.

Conclusions

The doubled fracture rate and the high incidence of skeletal complications during the first years after diagnosis suggest the developing skeleton is very vulnerable in this period. Adolescents develop more ON whereas younger children may be more prone to fractures. Serious “immediate effects” of chemotherapy on bone appear of great concern and should entail preventative studies in this group of patients. Pediatr Blood Cancer 2007;48:21–27. © 2005 Wiley‐Liss, Inc.
Rotation barriers in condensed rings: an extension of Clar's stability rule
Authors: Chuchev Krum , BelBruno Joseph J.
Published: November 2005

The rotation barrier for a substituent OH in systems of condensed benzene rings was studied using density functional theory. The barrier height depends on the position of the hydroxy group and the number of independent benzene rings in the condensed ring system, in agreement with Clar's π‐electron sextet stability model. Investigating OH‐derivatized polycenes with as many as 19 condensed rings showed that increasing the total size of the system does not contribute significantly to the rotation barrier. Copyright © 2005 John Wiley & Sons, Ltd.
Plasticized polylactide/clay nanocomposites. I. The role of filler content and its surface organo‐modification on the physico‐chemical properties
Authors: Pluta Miroslaw , Paul Marie‐Amélie , Alexandre Michaël , Dubois Philippe
Published: November 2005

Polylactide (PLA)‐layered silicate nanocomposites plasticized with 20 wt % of poly(ethylene glycol) 1000 were prepared by melt blending. Three kinds of organo‐modified montmorillonites—Cloisite® 20A, Cloisite® 25A, and Cloisite® 30B—were used as fillers at a concentration level varying from 1–10 wt %. Neat PLA and plasticized PLA with the same thermomechanical history were considered for comparison. Nanocomposites based on amorphous PLA were obtained via melt‐quenching. The influence of both plasticization and nanoparticle filling on the physicochemical properties of the nanocomposites were investigated. Characterization of the systems was achieved by size exclusion chromatography (SEC), thermogravimetric analysis (TGA), thermally modulated differential scanning calorimetry (TMDSC), X‐ray diffraction (XRD), and dynamic mechanical analysis (DMTA). SEC revealed a decrease of the molecular weight of the PLA matrix with the filler content. Thermal behavior on heating showed one cold crystallization process in the reference neat PLA sample, while two cold crystallization processes in plasticized PLA and plasticized nanocomposites. The thermal windows of these processes tend to increase with the filler content. The crystalline form of PLA developed upon heating was affected neither by the plasticization nor by the type and content of Cloisite used. It was found that the series of organo‐modified montmorillonites with decreasing affinity to PLA is Cloisite® 30B, Cloisite® 20A, and Cloisite® 25A, respectively. The dynamic mechanical properties were sensitive to the sample composition. Generally, the storage modulus increased with the filler content. Glassy PEG, well dispersed within unfilled PLA matrix, exhibited also a reinforcing effect, since the storage modulus of this sample was higher than for unplasticized reference at temperature region below the glass transition of PEG. Moreover, loss modulus of all plasticized samples revealed an additional maximum ascribed to the glass transition of PEG–rich dispersed phase, indicating partial miscibility of organic components of the systems investigated. The magnitude of this mechanical loss was correlated with the filler content, and to some extent, also with the nanofiller ability to be intercalated by polymer components. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 299–311, 2006