bluuebunny/crossref_metadata_2025 huggingface dataset:
Between Post‐nationalism and Neo‐institutionalism: The Structuring of Public Debates in Switzerland in the Field of Immigration and Ethnic Relations
Authors: Giugni Marco , Passy Florence
Published: February 2011

This article attempts to assess the relevance of post‐nationalist and neo‐institutionalist theories to explain the structuring of public debates on immigration and ethnic relations in Switzerland. To escape the contradictory debate existing between proponents of these two theoretical perspectives, but above all to improve our knowledge of processes of globalization and of resistance by nation‐states in the field of migrations, we propose a systematic analysis of public debates in this field during the 1980s. This allows us to assess the impact of external pressures and of national traditions on the treatment of migration issues. Our analysis unveils three changes that may attest to the impact of transnationalization of migration issues on national states. First, an important growth of debates on issues concerning the integration of immigrants took place, especially in the field of the fight against discriminations. Second, there was a more active participation of immigrants in the national public debates. Third, variations in the activity of the extreme right and the Swiss People's Party occurred, and more precisely a growth of the latter. In particular, the introduction of the Law against racism provided a window of opportunities for the Swiss political actors. Thus, within the constraining framework represented by the nation‐state, which yields political resources and a structure of legitimacy for the intervention of political actors in the field of immigration and ethnic relations, transnational forces are a source of variations and changes which should not be overlooked. In particular, the introduction of a transnational anti‐discrimination norm provides other types of political resources and another structure of legitimacy. Finally, our analysis suggests that the development of personhood rights at a supranational level can be a source of change that yields new models and new scripts for the action of national actors.
Malformation spectrum induced by ketoconazole after single administration to pregnant rats during the critical period – comparison with vitamin A‐induced malformation spectrum
Authors: Mineshima Hiroshi , Fukuta Tetsuya , Kato Emiko , Uchida Keiji , Aoki Toyohiko , Matsuno Yoshiharu , Mori Chisato
Published: February 2011

Azole derivatives have teratogenic effects in rodents. In the present study, malformations and their sensitive windows induced by high‐dose ketoconazole (KCZ), an azole derivative, without maternal toxicity were investigated. In addition, the malformation spectrum determined was compared with that induced by vitamin A palmitate (VAP). Pregnant rats were administered a single dose of KCZ by oral gavage on specific individual days from gestational days 8 to 15 (GDs 8–15). Maternal animals were subjected to necropsy on GD 20, and the obtained fetuses were examined for external, visceral and skeletal malformations. The malformation spectrum of VAP was identified from available published data (Noda, Sato, and Udaka, 1982) and a complementary study (single administration of VAP at 1 200 000 IU kg−1). Embryonic lethality was observed in dams given KCZ on GDs 9–12 with peak incidence on GDs 10 and 11 with complete resorption. KCZ induced major malformations included cleft palate, digital anomalies, misshapen limbs and unique discontinuous ribs, and the sensitive window for each was identified. Compared with the malformations induced by VAP, unique malformations (e.g. discontinuous ribs by KCZ, neural tube defects by VAP), similar malformations with similar sensitive windows (e.g. digital and limb malformations) and similar malformations with different sensitive windows (e.g. embryonic lethality and cleft palate) were distinguished, suggesting that the mechanisms of several of the types of KCZ‐induced malformation are related to excessive vitamin A. Copyright © 2011 John Wiley & Sons, Ltd.
Toxicological effect of emodin in mouse testicular gene expression profile
Authors: Oshida Keiyu , Hirakata Mikito , Maeda Akihisa , Miyoshi Tomoya , Miyamoto Yohei
Published: February 2011

Emodin (1,3,8‐trihydroxy‐6‐methyl‐anthraquinone) is a herbal medicine extracted from the rhizomes of Rheum palmatum, and is known as an inhibitor of casein kinase II (CK2). The CK2α′ knockout mice are known to be male‐infertile; however, there have been no reports on the toxicity of emodin in male reproductive organs/tissues. To evaluate the toxicological effects of emodin on differential gene expression profiles of the testis as compared with acrylamide, mice were orally administered emodin and acrylamide for 5 days at a dose of 1000 and 50 mg kg−1 per day, respectively, and euthanized 24 h after the final administration. Both chemicals induced hypospermatogenesis, eosinophilic change and apoptosis of germ cell. A DNA microarray analysis showed that the IGF‐1 receptor signaling was most closely related to the above testicular toxicity induced by emodin, and the RhoA regulation, TGF/WNT and cytoskeletal remodeling, TNFR1 signaling and adenosine A2A receptor signaling were commonly associated with the two chemicals. We selected 36 genes associated with CK2, apoptosis and spermatogenesis and determined their expression by quantitative reverse transcription‐polymerase chain reaction (qPCR). Both chemicals perturbed the expression of genes associated with CK2. Genes related to spermatogenesis were also affected, as evidenced by hypospermatogenesis, and eosinophilic change and apoptosis of germ cell. The results suggest that emodin causes testicular toxicity, including apoptosis with related the IGF‐1 receptor signaling pathway, and the two chemicals commonly affect CK2, spermatogenesis and sperm motility via four pathways, such as TNFR1 signaling. Copyright © 2011 John Wiley & Sons, Ltd.
The effects of metallothionein 2A polymorphism on placental cadmium accumulation: is metallothionein a modifiying factor in transfer of micronutrients to the fetus?
Authors: Tekin Deniz , Kayaaltı Zeliha , Aliyev Vugar , Söylemezoğlu Tülin
Published: February 2011

Metallothionein affects the metabolism, transport and storage of micronutrients such as zinc, copper and iron, and the detoxification of heavy metals, especially cadmium. Cd is a common, highly toxic environmental pollutant that accumulates in human placenta, elevated concentrations of which are associated with impaired zinc transfer to the fetus. This prospective study investigated the effects of metallothionein 2A (MT2A) −5 A/G single nucleotide polymorphism on the accumulation of Cd in human placenta and micronutrient transfer to the fetus in 95 pregnant women and their newborns. Venous blood from the mother was collected to investigate Cd, Zn, Cu, Fe levels and MT2A polymorphism. Cord blood from the neonate and placenta was collected for metal levels. MT2A polymorphism was determined by the standard PCR‐restriction fragment length polymorphism technique. Metal levels were analyzed by Atomic Absorption Spectrometry (AAS). Maternal blood Cd levels were statistically higher for mothers with a heterozygote genotype compared with a homozygote genotype (P < 0.05). In contrast, placental Cd levels were significantly higher in mothers with a homozygote rather than a heterozygote genotype (P < 0.05). No difference existed in cord blood Cd, Zn and Cu levels. However, cord blood Fe levels of newborns with heterozygote genotype mothers were higher than in others. Placental Cd levels of heterozygote genotype mothers were negatively associated with Zn in cord blood. Cd exposure at environmental levels may be associated with alteration of the umbilical cord micronutrient levels for newborns with mothers of a heterozygote genotype. Copyright © 2011 John Wiley & Sons, Ltd.
Biomaterials coated by dental pulp cells as substrate for neural stem cell differentiation
Authors: Soria Jose Miguel , Sancho‐Tello María , Esparza M. Angeles Garcia , Mirabet Vicente , Bagan Jose Vicente , Monleón Manuel , Carda Carmen
Published: February 2011

This study is focused on the development of an in vitro hybrid system, consisting in a polymeric biomaterial covered by a dental pulp cellular stroma that acts as a scaffold offering a neurotrophic support for the subsequent survival and differentiation of neural stem cells. In the first place, the behavior of dental pulp stroma on the polymeric biomaterial based on ethyl acrylate and hydroxy ethyl acrylate copolymer was studied. For this purpose, cells from normal human third molars were grown onto 0.5‐mm‐diameter biomaterial discs. After cell culture, quantification of neurotrophic factors generated by the stromal cells was performed by means of an ELISA assay. In the second place, survival and differentiation of adult murine neural stem cells on the polymeric biomaterials covered by dental pulp stromal cells was studied. The results show the capacity of dental pulp cells to uniformly coat the majority of the material's surface and to secrete neurotrophic factors that become crucial for a subsequent differentiation of neural stem cells. The use of stromal cells cultured on scaffolding biomaterials provides neurotrophic pumps that may suggest new criteria for the design of cell therapy experiments in animal models to assist the repair of lesions in Central Nervous System. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
The role of TLE1 in synovial sarcoma
Authors: Seo Sung Wook , Lee Hyewon , Lee Hyun‐Il , Kim Han‐Soo
Published: February 2011

The treatment outcome of synovial sarcoma is poor owing to its resistance to radiation and chemotherapy. The Transducin‐like Enhancer of Split 1 (TLE1) is a co‐repressor that involves many signaling pathways like cell survival, hematopoiesis and differentiation. Although TLE1 is uniquely expressed in synovial sarcomas, the biological role of TLE1 is not completely understood. This study evaluated the function of TLE1 in synovial sarcomas using knock‐down of TLE1, and examined whether the inhibition of TLE1 suppresses the proliferation of synovial sarcomas and enhances the cytotoxicity caused by doxorubicin (doxo). The over‐expression of TLE1 was first confirmed in synovial sarcoma cells (HS‐SYII). When the HS‐SYII cells and normal fibroblast were transiently transfected with TLE1 siRNA, the MTT assay revealed growth inhibition in the HS‐SY‐11 cells but not in the normal fibroblast. TLE1 silencing also potentiated the cytotoxic effects of doxo against HS‐SYII cells. This effect of TLE1 silencing was attributed mainly to the induction of apoptosis. Subsequent analysis revealed that Bcl‐2 is a possible downstream target of TLE1 signaling. This study demonstrated that TLE1 is a critical factor for the survival of synovial sarcomas. Overall, the inhibition of TLE1 affects cell proliferation and the apoptosis pathway by suppressing the expression of Bcl‐2. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1131–1136, 2011
Rapid detection of a foreign protein in milk using IMS–SERS
Authors: He Lili , Haynes Christy L. , Diez‐Gonzalez Francisco , Labuza Theodore P.
Published: February 2011

A method for rapid detection of foreign protein contamination in complex food matrices is critically needed. Here we present a novel method that combines immunomagnetic separation (IMS) and surface‐enhanced Raman scattering (SERS) to detect ovalbumin (OVA), an egg white protein, added into whole milk. IMS was used to specifically capture the OVA out of the milk. Then SERS was applied to analyze the IMS eluate using silver dendrites as the substrate. Two SERS sample preparation methods, namely solution based and substrate based, were used to prepare the IMS eluate for SERS analysis. Results show both methods were able to detect 1 µg OVA in 1 ml milk (1 part per million). Based on the results of principal component analysis and partial least‐squares analysis, solution SERS was more capable of quantitative analysis, while substrate SERS was more sensitive for qualitative analysis. The total analytical time for IMS–SERS was less than 20 min, which satisfied the requirement of rapid detection in a milk processing facility. Copyright © 2011 John Wiley & Sons, Ltd.
Simultaneous determination of 13 phytohormones in oilseed rape tissues by liquid chromatography‐electrospray tandem mass spectrometry and the evaluation of the matrix effect
Authors: Fan Sufang , Wang Xiupin , Li Peiwu , Zhang Qi , Zhang Wen
Published: February 2011

In the experiment, a high‐performance liquid chromatography and electrospray ionization‐tandem mass spectrometry with selected reaction monitoring was used to simultaneously determine various classes of phytohormones, including indole‐3‐acetic acid, α‐naphthaleneacetic acid, 2‐chlorobenzoic acid, 4‐chlorobenzoic acid, indole‐3‐butyric acid, gibberellic acid, 2,4‐dichlorophenoxyacetic acid, 2‐naphthoxyacetic acid, abscisic acid, 2,3,5‐triiodobenzoic acid, uniconazole, paclobutrazol and 2,4‐epibassinolide in rape tissues. The analyses were separated by an HPLC equipped with a reversed‐phase column using a binary solvent system composed of methanol and water, both containing 0.1% of formic acid. The matrix effect was also considered and determined. The technology was applied to analyze rape tissues, including roots, stems, leaves, flowers, immature pods and rape seeds. The rape tissues were subjected to ultrasound‐assisted extraction and purified by dispersive solid‐phase extraction, and then transferred into the liquid chromatography system. The detection limit for each plant hormone was defined by the ratio of signal/background noise (S/N) of 3. The results showed perfect linearity (R2 values of 0.9987–1.0000) and reproducibility of elution times (relative standard deviations, RSDs,<1%) and peak areas (RSDs,<7%) for all target compounds.
Comparison of liver mitochondrial proteins derived from newborn cloned calves and from cloned adult cattle by two‐dimensional differential gel electrophoresis
Authors: Takeda Kumiko , Tasai Mariko , Akagi Satoshi , Watanabe Shinya , Oe Mika , Chikuni Koichi , Ohnishi‐Kameyama Mayumi , Hanada Hirofumi , Nakamura Yoshiaki , Tagami Takahiro , Nirasawa Keijiro
Published: February 2011

Aberrant reprogramming of donor somatic cell nuclei may result in many severe problems in animal cloning. The inability to establish functional interactions between donor nucleus and recipient mitochondria is also likely responsible for such a developmental deficiency. However, detailed knowledge of protein expression during somatic cell nuclear transfer (SCNT) in cattle is lacking. In the present study, variations in mitochondrial protein levels between SCNT‐derived and control cattle, and from calves derived by artificial insemination were investigated. Mitochondrial fractions were prepared from frozen liver samples and subjected to two‐dimensional (2‐D) fluorescence differential gel electrophoresis (DIGE) using CyDye™ dyes. Protein expression changes were confirmed with a volume ratio greater than 2.0 (P < 0.05). 2D‐DIGE analysis revealed differential expression of three proteins for SCNT cattle (n = 4) and seven proteins for SCNT calves (n = 6) compared to controls (P < 0.05). Different protein patterning was observed among SCNT animals even if animals were generated from the same donor cell source. No differences were detected in two of the SCNT cattle. Moreover, there was no novel protein identified in any of the SCNT cattle or calves. In conclusion, variation in mitochondrial protein expression concentrations was observed in non‐viable, neonatal SCNT calves and among SCNT individuals. This result implicates mitochondrial‐related gene expression in early developmental loss of SCNT embryos. Comparative proteomic analysis represents an important tool for further studies on SCNT animals. Mol. Reprod. Dev. 78:263–273, 2011. © 2011 Wiley‐Liss, Inc.
An artificial compressibility CBS method for modelling heat transfer and fluid flow in heterogeneous porous materials
Authors: Malan A. G. , Lewis R. W.
Published: February 2011

This work is concerned with the development of an artificial compressibility version of the characteristic‐based split (CBS) method proposed by Zienkiewicz and Codina (Int. J. Numer. Meth. Fluids 1995; 20:869–885). The technique is applied to modelling both forced convection as well as heat transfer and fluid flow through heterogeneous saturated porous materials via an edge‐based finite volume discretization scheme. A volume‐averaged set of local thermal disequilibrium governing equations is employed to describe the general case which allows for the modelling of effects such as wall channelling and wall‐bed radiative heat transfer. The resulting set of coupled non‐linear partial differential equations is solved in a matrix‐free manner with spatial discretization being effected with a compact vertex‐centred finite volume edge‐based discretization scheme. The latter was done in the interest of efficiency and accuracy. The developed scheme is validated via application to problems ranging from forced convection to natural convection in heterogeneous materials, and shown to be stable, robust and accurate. Copyright © 2011 John Wiley & Sons, Ltd.
RK‐Slim: embedded Runge–Kutta without the excess baggage
Authors: Canedo Arquimedes , Yoshizawa Takeo , Komatsu Hideaki , Kobayashi Mei
Published: February 2011

Computationally demanding scientific simulations require numerical integration of large systems of ordinary differential equations (ODEs) in real time. Runge–Kutta (RK) methods with step‐size control are frequently employed because they are accurate and have short execution times. Computational step sizes can be increased while maintaining accuracy if the error generated during each time step is below a predetermined threshold. However, if the error exceeds the threshold, the time step must be re‐computed using a smaller step‐size. In practice, the re‐computation is unnecessary for most equations in the system because violations of the error tolerance are localized and occur in just a few equations. We present an efficient and accurate method for solving ODEs that exploits these observations on step‐size by eliminating many unnecessary computations in embedded RK methods. We demonstrate how our new method can be a valuable tool for practitioners in the field through simulations with real‐world data. Copyright © 2011 John Wiley & Sons, Ltd.
Successful campaigning: Winning friends and influencing people
Authors: Parminter Kate
Published: February 2011

This paper discusses the move of charities into campaigning as a means of meeting their objectives. It outlines ways, within Charity Commission guidelines, to seek to secure legislative change. Several case histories demonstrate the approach outlined and the potential for success.
Challenges of coping with a nationwide television appeal: Norway
Authors: Ellis Gilbert
Published: February 2011

Fundraising ‘telethons’ are run by many countries, but Norwegian television's annual campaign is a major country‐wide event. In 1995 The Salvation Army in Norway was designated to be the beneficiary and this paper outlines the organisation of its campaign. A greatly enlarged database was necessary and the IT system used for this is described, as is an innovative telephone donation system devised by Telenor. Acknowledgement of donors and their registration on the database was followed up six months later and the responses to this follow‐up are analysed. Conclusions are drawn on the financial results of the campaign.
Giving donors good reason to give again
Authors: Mcgrath Simon
Published: February 2011

The donor bases of many charities suffer high lapse rates that both restrict growth and carry a heavy cost in recruitment needed to replace the lost donors. This paper argues that it should be possible to reduce these high lapse rates, based on the experience of businesses that have reduced their lapse rates by giving customers better value. Giving customers good value gives them good reason to come back for more. The paper looks at evidence that donors, like customers, want satisfaction in return for their money. The paper proposes a model of donor value to identify how charities can give donors more for their money, providing a route to reduce lapsing and so improve charity profitability and growth.
Turning data into donations: A predictive model for individual giving
Authors: Toohill Jim , Mullins Lisa , Barclay Jean , Sadnicki Mike
Published: February 2011

This paper describes a predictive model developed by the Royal National Institute for Deaf People (RNID) for the evaluation of donor management strategies. The high cost of acquiring new donors means that effective donor management is essential throughout the charity sector. Early RNID analysis of donor behaviour used conventional sector approaches. This led to the development of a predictive model that uses a statistically determined segmentation system for current donors with responses of the donor base described by a Markov model. The model is used primarily to evaluate the expected rate of return of possible campaign strategies, but there are many other ways in which the approach is of value, both to the RNID and to the charity sector as a whole.
The marketing cycle for a not‐for‐profit
Authors: Brinckerhoff Peter C.
Published: February 2011

Marketing is a process, one with discrete and identifiable steps. This is true for both for‐profit and nonprofit organisations. However, many nonprofits are told what services or products they will provide, thus skipping the crucial first steps in the marketing process. This paper lays out a classical marketing cycle and shows its applications for nonprofit and voluntary organisations. Several examples are discussed.
Not‐for‐profit pressure group work: A marketing analysis of whether to operate solo or in coalition
Authors: Bruce Ian W.
Published: February 2011

Pressure (or interest or lobby) group work in charities/not‐for‐profits can benefit from a marketing approach. Product development, other player (competitor) analysis and positioning of the pressure group vis‐à‐vis associated and sometimes competitor organisations or groups are explored, as are the conditions (including advantages and disadvantages) under which solo versus coalition ways of working are likely to be most effective.
Strategic management and fundraising: A planning model for resource development in the nonprofit organisation
Authors: Hanson John H.
Published: February 2011

Many nonprofits can benefit greatly from integrating their strategic, marketing and fundraising planning into an environmentally comprehensive process. Even during this critical period for them, many nonprofits typically have failed to implement this type of integrated planning because their corporate culture often nurtures: an inner process focus, leadership pathologies, professional balkanisation, reluctance to accept advancement as a global organisational activity, an unwillingness to accept the realities of a moving market and a lack of political will to undertake social advocacy on behalf of their clients.

In order to succeed in the future, nonprofit organisations will need to approach strategic planning through an interdisciplinary methodology that will be shaped by multiple market audits focusing on: mission and institutional capabilities, image and competitive analysis, philanthropic feasibility and flexible integration of revenue/resource development.

Nonprofits that adopt this interdisciplinary process will be rewarded by enhanced fundraising returns, once re‐founded on a culture that has remained mission‐relevant while becoming market‐driven. The nonprofit that bases its planning on more effective use of intelligence gathering and flexible focusing of its human and financial capital will be more capable of acting upon a fluid environment and realising the institution's optimal future.
2‐DOF nonlinear ℋ︁∞ certainty‐equivalent filters (CEFs)
Authors: Aliyu M. D. S.
Published: February 2011

In this paper, a new theory of two‐degrees‐of‐freedom (2hbox − DOF) ℋ︁∞ filters as counterparts of 2‐DOF controllers is presented. The theory is also extended to n − DOF filters which bore strong resemblance to linear finite‐impulse‐response filters and hence generalizes this class of filters to the nonlinear continuous‐time case. Sufficient conditions for the solvability of the filter gains are derived in terms of new Hamilton–Jacobi–Isaacs equations which do not involve the system states. This is an improvement over earlier results in which the filter gains are functions of the system states. Simulation results are also presented to support the theory. Copyright © 2011 John Wiley & Sons, Ltd.
Basic helix‐loop‐helix transcription factor DEC1 negatively regulates cyclin D1
Authors: Bhawal Ujjal K , Sato Fuyuki , Arakawa Yuki , Fujimoto Katsumi , Kawamoto Takeshi , Tanimoto Keiji , Ito Yumi , Sasahira Tomonori , Sakurai Takashi , Kobayashi Masaru , Kashima Isamu , Kijima Hiroshi , Kuniyasu Hiroki , Abiko Yoshimitsu , Kato Yukio , Sato Sadao
Published: February 2011

DEC1 (also known as Stra13/Bhlhb2/Sharp2) and DEC2 (also known as Bhlhb3/Sharp1) are two paralogous basic helix‐loop‐helix (bHLH) transcriptional regulators which exhibit a robust circadian gene expression pattern in the suprachiasmatic nucleus (SCN) and in peripheral organs. DEC1 has been suggested to play key roles in mammalian cell differentiation, the cell cycle and circadian regulation, hypoxia response, and carcinogenesis. Here we show that DEC1 overexpression exhibits delayed wound healing and reduces cell proliferation, migration, and invasion. DEC1 strongly repressed the promoter activity of cyclin D1. We further identify a possible DEC‐response element in the cyclin D1 promoter region, and confirmed the direct binding of DEC1 to that element. Forced expression of DEC1 efficiently repressed the cyclin D1 promoter and expression. Our clinical data provide the first evidence that there is a strong inverse correlation between DEC1 and cyclin D1 expression in oral cancer, and DEC1 expression significantly correlated with clinicopathological parameters. We suggest that radiation‐induced DEC1 overexpression and Akt phosphorylation in cancer cells are mediated via PI‐3K signalling. Overexpression of DEC1 activates the PI‐3K/Akt signalling pathway through reactive oxygen species (ROS). Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Comprehensive analysis of CpG island methylator phenotype (CIMP)‐high, ‐low, and ‐negative colorectal cancers based on protein marker expression and molecular features
Authors: Zlobec Inti , Bihl Michel , Foerster Anja , Rufle Alex , Lugli Alessandro
Published: February 2011

CpG island methylator phenotype (CIMP) is being investigated for its role in the molecular and prognostic classification of colorectal cancer patients but is also emerging as a factor with the potential to influence clinical decision‐making. We report a comprehensive analysis of clinico‐pathological and molecular features (KRAS, BRAF and microsatellite instability, MSI) as well as of selected tumour‐ and host‐related protein markers characterizing CIMP‐high (CIMP‐H), ‐low, and ‐negative colorectal cancers. Immunohistochemical analysis for 48 protein markers and molecular analysis of CIMP (CIMP‐H: ≥ 4/5 methylated genes), MSI (MSI‐H: ≥ 2 instable genes), KRAS, and BRAF were performed on 337 colorectal cancers. Simple and multiple regression analysis and receiver operating characteristic (ROC) curve analysis were performed. CIMP‐H was found in 24 cases (7.1%) and linked (p < 0.0001) to more proximal tumour location, BRAF mutation, MSI‐H, MGMT methylation (p = 0.022), advanced pT classification (p = 0.03), mucinous histology (p = 0.069), and less frequent KRAS mutation (p = 0.067) compared to CIMP‐low or ‐negative cases. Of the 48 protein markers, decreased levels of RKIP (p = 0.0056), EphB2 (p = 0.0045), CK20 (p = 0.002), and Cdx2 (p < 0.0001) and increased numbers of CD8+ intra‐epithelial lymphocytes (p < 0.0001) were related to CIMP‐H, independently of MSI status. In addition to the expected clinico‐pathological and molecular associations, CIMP‐H colorectal cancers are characterized by a loss of protein markers associated with differentiation, and metastasis suppression, and have increased CD8+ T‐lymphocytes regardless of MSI status. In particular, Cdx2 loss seems to strongly predict CIMP‐H in both microsatellite‐stable (MSS) and MSI‐H colorectal cancers. Cdx2 is proposed as a surrogate marker for CIMP‐H. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Malignant fibrous histiocytoma two years after autologous stem cell transplant for Hodgkin lymphoma: Evidence for genomic instability
Authors: Chandrakasan Shanmuganathan , Ye Christine J. , Chitlur Meera , Mohamed Anwar N. , Rabah Raja , Konski Andre , Heng Henry H. Q. , Savaşan Süreyya
Published: February 2011

Secondary malignancies (SMs) in Hodgkin lymphoma (HL) are thought to be related to exposure to alkalating agents, topoisomerase II inhibitors and ionizing radiation, and tend to occur a decade after initial therapy. We report a 14 year old autistic male, who developed malignant fibrous histiocytoma (MFH) two years after autologous stem cell transplantation for advanced stage HL. The MFH and post‐surgical reactive tissues exhibited multiple clonal abnormalities. In addition, PHA‐stimulated peripheral blood lymphocytes showed increased frequency of non‐clonal chromosomal aberrations. The potential role of genomic instability in early onset of SM in our patient is discussed. Pediatr Blood Cancer 2011;56:1143–1145. © 2010 Wiley‐Liss, Inc.
Tele‐practice guidelines for the symptom management of children undergoing cancer treatment
Authors: Tsimicalis Argerie , De Courcy Mary Jo , Di Monte Bruna , Armstrong Christine , Bambury Patti , Constantin Julie , Dagelman Barbara , Eves Marilyn , Jansen Patty , Honeyford Lisa , Stregger Denise
Published: February 2011

The provision of tele‐practice symptom management is often without the provision of evidence‐based guidelines. Under the auspices of the Pediatric Oncology Group of Ontario, a nursing task force was established to appraise the evidence and develop guidelines. Promising new efforts to enhance symptom management through tele‐practice are emerging. Seven guidelines and one documentation tool were created from evidence compiled from case reports, clinical examples, and nonexperimental studies. The symptom management guidelines contribute to the paucity of literature and may serve as a useful resource for health professionals providing telephone advice and conducting tele‐practice symptom management assessments. Pediatr Blood Cancer 2011; 57: 541–548. © 2011 Wiley‐Liss, Inc.
Invasive fungal infections in pediatric oncology
Authors: Mor Meirav , Gilad Gil , Kornreich Liora , Fisher Salvador , Yaniv Isaac , Levy Itzhak
Published: February 2011

Background

Data on the epidemiology and outcome of invasive fungal infections in children with cancer are limited. The aim of the study was to delineate the epidemiologic, clinical features, risk factors, and outcome of invasive fungal infections in this population.

Procedure

The medical records of all children with malignancies diagnosed with an invasive fungal infection in 1998–2006 at a tertiary pediatric medical center were reviewed for demographic, clinical, and laboratory data. Invasive fungal infection was diagnosed according to the latest EORTC/MSG criteria.

Results

Of the 1,047 children hospitalized in the hematology/oncology department during the study period, 75 (7.2%) were diagnosed with a proven (n = 16, 21.3%), probable (n = 18, 24%), or possible (n = 41, 54.7%) invasive fungal infection. Fifteen (20%) had candidemia (non‐albicans in 60%), and 60 (80%) had a mold infection (non‐Aspergillus in 55%). Crude mortality was 21.7%. The most common underlying diseases were myeloid leukemia (n = 26, 34.7%) and acute lymphoblastic leukemia (n = 24, 32%). Compared to other malignancies, acute myeloid leukemia was significantly associated with the development of invasive fungal infections. Profound neutropenia and high treatment intensity were present in 89% and 73% of patients with IFI respectively.

Conclusions

The current mortality rates of invasive fungal infection in children with cancer are lower than previously reported in children and adults. However, the proportion of non‐albicans candidemia is increasing, and non‐Aspergillus molds are emerging as important pathogens, which may have important implications for prophylaxis and empiric therapy. Improved prevention, early detection, and advanced treatment strategies are needed to improve the outcome. Pediatr Blood Cancer 2011;56:1092–1097. © 2011 Wiley‐Liss, Inc.
A cross‐sectional study of overweight in pediatric survivors of acute lymphoblastic leukemia (ALL)
Authors: Love Erin , Schneiderman Jane E. , Stephens Derek , Lee Sylvia , Barron Mary , Tsangaris Elena , Urbach Stacey , Staneland Patricia , Greenberg Mark , Nathan Paul C.
Published: February 2011

Background

Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for overweight, predisposing them to long‐term morbidity. We examined the relationship between body mass index (BMI) and demographic and lifestyle factors in a cohort of ALL survivors.

Procedure

We enrolled consecutive ALL survivors who attended the institutional AfterCare Clinic over a 1‐year period. BMI (kg/m2) at diagnosis, end‐therapy, and current time were calculated. Survivors were classified as overweight/obese (overweightgroup; BMI for age ≥85th percentile) or normal/underweight (normalweight group; BMI for age <85th percentile). We assessed the relationship between current BMI and self‐reported current caloric intake, physical activity, and sedentary behavior.

Results

102/157 (65%) eligible survivors consented to enrollment. Median age was 14.3 years (range 8.4–18.6) and time from end of treatment 7 years (2.5–15.6). The proportion of overweight survivors was 21%, 45%, and 35% at diagnosis, end‐therapy, and current time, respectively. The overweight group reported less calories (Δ324 kcal,P = 0.018), fat (Δ14.5 g,P = 0.02), and carbohydrates (Δ39 g,P = 0.02) than the normal weight group. These differences disappeared after excluding patients classified as under‐reporting their calorie intake according to the Goldberg cut‐off method. There were no differences in sedentary behavior or activity between groups.

Conclusions

Many children with ALL gain weight during therapy and fail to return to normal weight after treatment concludes. Subsequent diet, physical activity, and sedentary behavior do not appear to differ between overweight and normal weight survivors. Clinicians should focus on ways to minimize weight gain during therapy rather than waiting for treatment to conclude. Pediatr Blood Cancer 2011; 57: 1204–1209. © 2011 Wiley Periodicals, Inc.
Preclincial testing of Sorafenib and RAD001 in the Nfflox/flox;DhhCre mouse model of plexiform neurofibroma using magnetic resonance imaging
Authors: Wu Jianqiang , Dombi Eva , Jousma Edwin , Scott Dunn R. , Lindquist Diana , Schnell Beverly M. , Kim Mi‐Ok , Kim AeRang , Widemann Brigitte C. , Cripe Timothy P. , Ratner Nancy
Published: February 2011

Background

Neurofibromatosis type 1 (NF1) is an inherited disease predisposing affected patients to variable numbers of benign neurofibromas. To date there are no effective chemotherapeutic drugs available for this slow growing tumor. Molecularly targeted agents that aim to slow neurofibroma growth are being tested in clinical trials. So preclinical models for testing potential therapies are urgently needed to prioritize drugs for clinical trials of neurofibromas.

Procedure

We used magnetic resonance imaging (MRI) to monitor neurofibroma development in the Nf1flox/flox;DhhCre mouse model of GEM grade I neurofibroma. Based on studies implicating mTOR and Raf signaling in NF1 mutant cells, we tested the therapeutic effect of RAD001 and Sorafenib in this model. Mice were scanned to establish growth rate followed by 8 weeks of drug treatment, then re‐imaged after the last dose of drug treatment. Tumor volumes were determined by volumetric measurement.

Results

We found that rate of tumor growth varied among mice, as it does in human patients. RAD001 inhibited its predicted target pS6K, yet there was no significant decrease in the tumor volume in RAD001 treated mice compared to the vehicle control group. Sorafenib inhibited cyclinD1 expression and cell proliferation in tumors, and volumetric measurements identified significant decreases in tumor volume in some mice.

Conclusion

The data demonstrate that volumetric MRI analysis can be used to monitor the therapeutic effect in the preclinical neurofibroma drug screening, and suggest that Sorafenib might have clinical activity in some neurofibromas. Pediatr Blood Cancer 2012; 58: 173–180. © 2011 Wiley Periodicals, Inc.
Five‐year single‐center study of asparaginase therapy within the ALL‐BFM 2000 trial
Authors: Schrey Dominik , Speitel Katharina , Lanvers‐Kaminsky Claudia , Gerss Joachim , Möricke Anja , Boos Joachim
Published: February 2011

Background

Therapeutic drug monitoring (TDM) of asparaginase (ASNase), a fundamental element of acute lymphoblastic leukemia treatment, was integrated in the ALL‐BFM 2000 protocol on a voluntary basis.

Methods

Over a 5‐year period, 127 patients (1,355 samples) were monitored for asparaginase activity in a single‐center setting. We report monitoring data from throughout the ASNase containing treatment elements. Additional information obtained on risk stratification, minimal residual disease (MRD), steroid randomization and relapse is discussed in relation to ASNase activity.

Results

At completion of the induction phase 93% (115/124) of patients showed sufficient ASNase activity (5,000 U/m2 Escherichia coli ASNase), 77 of 86 (90%) monitored patients finished the first re‐intensification element without requiring Erwinia ASNase. MRD, risk stratification and steroid randomization were not associated with significant differences in ASNase activity. Of patients who relapsed, only 25% (3/12) were able to maintain sufficient ASNase activity after E. coli ASNase.

Conclusion

This single‐center data set gives a true and unbiased insight into clinical reality of ASNase therapy. It shows no significant relationship between MRD positivity or risk stratification and ASNase treatment intensity. Overall, within the ALL‐BFM 2000 trial, 90% of patients completed first re‐intensification without requiring third‐line Erwinia ASNase. Pediatr Blood Cancer 2011; 57: 378–384. © 2011 Wiley‐Liss, Inc.
Evaluation of the degree of dispersion of nanofillers by mechanical, rheological, and permeability analysis
Authors: Corcione Carola Esposito , Cavallo Anna , Pesce Emanuela , Greco Antonio , Maffezzoli Alfonso
Published: February 2011

The aim of this paper is a comparison of the effectiveness of different macrocharacterization techniques for the prediction of the degree of dispersion and intercalation of bidimensional nanofillers in an amorphous thermoplastic matrix. Organically modified montmorillonites (omMMT) were used as bidimensional nanofillers, whereas amorphous polyethylene‐terephthalate copolymer (PETg) was used as matrix. Wide angle x‐ray diffraction analysis showed no relevant difference between the samples processed at different temperatures, all characterized by a predominantly intercalated structure. On the other hand, transmission electron microscopy (TEM) analysis showed the presence of some degree of exfoliation, as well as the presence of lamellar stacks of different thickness. The aspect ratio of lamellar stacks was estimated by means of rheological, mechanical, and gas permeability analysis. All techniques provided values which are in quite good agreement with TEM analysis. Furthermore, all techniques were able to capture the increase in the lamellar stack aspect ratio with decreasing processing temperature. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers
Amphiphilic Copolymer Coatings via Plasma Polymerisation Process: Switching and Anti‐Biofouling Characteristics
Authors: Kumar Virendra , Pulpytel Jerome , Giudetti Guido , Rauscher Hubert , Rossi Francois , Arefi‐Khonsari Farzaneh
Published: February 2011

Environmentally benign‐solvent free plasma process is employed to produce nanostructured PFDA‐co‐DEGDME amphiphilic coatings via plasma co‐polymerisation of 1H,1H,2H,2H‐perfluorodecyl acrylate (PFDA) and diethyleneglycol dimethyl ether (DEGDME) precursors in a low pressure‐RF‐inductively excited tubular plasma reactor using argon as a carrier gas. The plasma‐polymerised coatings are characterised by Fourier transform infrared spectroscopy (FT‐IR), X‐ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM) and contact angle measurements. PFDA‐co‐DEGDME coatings with varying chemical environments and morphologies are achieved by varying the plasma parameters such as, continuous wave (CW) and pulse modulated (PM) plasma mode, and plasma deposition time. Plasma polymerised PFDA‐co‐DEGDME coatings are found to exhibit a switching property in terms of wettability, i.e., from hydrophobic to hydrophilic and vice versa, in response to the contacting environment. Quartz crystal microbalance (QCM) is used to study the adhesion of two model proteins, namely, human serum albumin (HSA) and fibrinogen (FGN) in continuous flow conditions, which reveals the protein repellent, i.e., anti‐biofouling characteristics of the PFDA‐co‐DEGDME amphiphilic coatings.

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The effect of early Pseudomonas aeruginosa treatment on lung function in pediatric cystic fibrosis
Authors: Amin Reshma , Lam Michelle , Dupuis Annie , Ratjen Felix
Published: February 2011

Objective

Our aim was to assess the effect of treatment of early infection of P. aeruginosa on pulmonary function in pediatric CF patients.

Methods

This was a retrospective cohort study of P. aeruginosa negative CF patients followed at Sick Kids from 1990 to 2007. Early P. aeruginosa infection was defined as the first respiratory culture for P. aeruginosa; patients were included if 5 years of follow‐up pulmonary function data were available. Patients were divided into three groups (group 1: never infected, group 2: infected with subsequent clearance, and group 3: chronic infection or still receiving antipseudomonal antibiotics). Hierarchical linear models were used to estimate the effect of P. aeruginosa infection on spirometry. FEV1% predicted was the primary outcome.

Results

116 patients were included. Forty‐six (40%) patients remained P. aeruginosa negative throughout the observation period, 29 (25%) patients transiently infected with P. aeruginosa, and 41 (35%) patients were either currently infected or still receiving treatment. Baseline lung function was the same for all groups. Annual decline in FEV1% predicted during the study period was not different (−0.6%/year for patients that were never infected and −1.3%/year among patients previously infected).

Conclusions

Lung function was not different between patients with early P. aeruginosa infection and those that never had P. aeruginosa infection. However given the slow rate of FEV1 decline in the study population, a longer observation period and/or more sensitive outcomes measures may be required to exclude long‐term detrimental effects of transient P. aeruginosa infection on lung function in CF patients. Pediatr. Pulmonol. 2011; 46:554–558. © 2011 Wiley‐Liss, Inc.
Comparison of mechanical ventilatory constraints between continuous and intermittent exercises in healthy prepubescent children
Authors: Borel Benoit , Leclair Erwan , Thevenet Delphine , Beghin Laurent , Gottrand Frédéric , Fabre Claudine
Published: February 2011

Background

The aim of this study was to evaluate the occurrence and severity of mechanical ventilatory constraints in healthy prepubescent children during continuous and intermittent exercise.

Methods

Twelve prepubescent children (7–11 years old) performed 7 exercises on a treadmill: one graded test for the determination of maximal aerobic speed (MAS), three continuous exercises (CE) at 60, 70, and 80% of MAS and three intermittent exercises (IE), alternating 15 sec of exercise with 15 sec of passive recovery, at 90, 100, and 110% of MAS. During each CE and IE, tidal flow/volume loops were plotted within a maximal flow/volume loop (MFVL) measured at rest before each exercise. Expiratory flow limitation (expFL expressed in %Vt) was defined as the part of exercise tidal volume (Vt) meeting the boundary of MFVL. Breathing strategy was estimated by measuring inspiratory capacity relative to forced vital capacity and tidal volume relative to inspiratory capacity. Other breathing pattern parameters (ventilation VE, Vt, respiratory frequency f) were continuously recorded during exercise.

Results

An “intensity” effect was found for ${\dot {\rm {V}}E}$ during CE (P < 0.001) but not during IE (P = 0.08). The increase in ${\dot {\rm {V}}E}$ was predominantly assumed by an increase in f for both exercise modalities. During each exercise, several children heterogeneously experienced expFL ranging between 10 and 90%Vt. For all exercises, Vt was predominantly regulated by an increase in Vt/IC with no change in IC/FVC from rest to exercise. Finally, no significant “modality” effect was found for mechanical ventilatory constraint parameters (expFL, Vt/IC, and IC/FVC).

Discussion

We could conclude that neither of the modalities studied induced more mechanical ventilatory constraints than the other, but that exercise intensities specific to each modality might be greater sources of exacerbation for mechanical ventilatory constraints. Pediatr. Pulmonol. 2011; 46:785–794. © 2011 Wiley‐Liss, Inc.
Polymorphisms in GSDMA and GSDMB are associated with asthma susceptibility, atopy and BHR
Authors: Yu Jinho , Kang Mi‐Jin , Kim Byoung‐Ju , Kwon Ji‐Won , Song Young‐Hwa , Choi Won‐Ah , Shin Yee‐Jin , Hong Soo‐Jong
Published: February 2011

The gasdermin A (GSDMA) and gasdermin B (GSDMB) genes are located at 17q21.2. The GSDM family genes have been studied in the gastrointestinal tract but recent reports suggest that GSDMB is associated with childhood asthma in several populations. We investigated the association of the GSDMA and GSDMB variants with asthma in Korean children, and to assess the effect of these variants on intermediate phenotypes of asthma. Asthmatic (n = 778) and normal (n = 522) children were enrolled and genotypes were determined using PCR‐RFLP. Asthma susceptibility was associated with GG of the GSDMA (rs7212938) and TT of GSDMB (rs7216389). And a combination of risk alleles of two polymorphisms was associated with asthma susceptibility and a frequency of those was higher in asthmatic children with increased levels of total IgE (aOR 1.77, 95% CI 1.15–2.72) and BHR (aOR 1.54, 95% CI 0.99–2.40) compared to normal. Also, we observed a significant association between haplotype of two polymorphisms and asthma susceptibility. The region including the GSDMA and GSDMB polymorphisms may be associated with asthma susceptibility and intermediate phenotypes of asthma, such as elevated IgE and BHR, in Korean children with asthma. These results strongly support an important role for the GSDMA and GSDMB in the development of childhood asthma. Pediatr. Pulmonol. 2011; 46:701–708. © 2011 Wiley‐Liss, Inc.