bluuebunny/crossref_metadata_2025 huggingface dataset:
Photocrosslinked DNA Nanospheres for Drug Delivery
Authors: Roh Young Hoon , Lee Jong Bum , Tan Shawn J. , Kim Bojeong , Park Hyeongsu , Rice Edward J. , Luo Dan
Published: May 2010

DNA has been employed as both a genetic and a generic material. X‐shaped DNA (X‐DNA) in particular has four branched arms, providing multivalent functionalities that can allow for simultaneous multiple crosslinking. Here we report the synthesis of four acrylate‐functionalized X‐DNA monomers that can be further photocrosslinked to form monodisperse and tunable DNA nanospheres. In particular, the size and surface charge of these nanospheres were precisely controlled in a linear fashion, simply by tuning the monomer concentration in the reaction. The morphology and surface properties of the nanospheres were characterized using FT‐IR, HPLC, TEM, AFM, zeta potential, and DLS analysis. In vitro studies in mammalian cells revealed that these DNA nanospheres demonstrated significant efficacy in the delivery of doxorubicin. These results highlight the potential of using DNA as material building blocks to design novel nanocarriers with properties tailored for the delivery of drugs in general and DNA/RNA in particular.

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Breast cancer prevention based on gene–environment interaction
Authors: Song Minkyo , Lee Kyoung‐Mu , Kang Daehee
Published: May 2010

Breast cancer, the most common cancer in women, results from combined effects of genetic and environmental factors. Although a number of preventive measures have been suggested to reduce the risk of breast cancer, only a few (e.g., regular mammogram, etc.) proved to be efficient preventive modalities. Among many potential reasons, differences in individual susceptibility factors may complicate the efficacy of the intervention. A growing body of evidence shows that the strength of association between various dietary, behavioral (exercise and obesity), and environmental exposures, and breast cancer risk may be modified by individual genetic factors. Preventive strategies against breast cancer will be discussed considering the findings of the gene–environment interaction of breast cancer. These include behavior modification for high‐risk subjects (primary prevention), early detection and extensive monitoring of genetically susceptible subjects and noninvasive treatment of early stage cancer cases (secondary prevention), and finally prophylactic and therapeutic intervention to slow the progression of diseases (tertiary prevention). The accumulating evidences of the gene–environment interactions provide a better understanding of the breast cancer development and enable us to adopt individualized preventive strategies for personalized health care. © 2010 Wiley‐Liss, Inc.
Hypokinesia in Huntington's disease co‐occurs with cognitive and global dysfunctioning
Authors: Reedeker Nanda , Van Der Mast Rose C. , Giltay Erik J. , Van Duijn Erik , Roos Raymond A.C.
Published: May 2010

Besides chorea, hypokinesia is an important motor disturbance in Huntington's disease (HD) but its clinical, neuropsychiatric, and cognitive functioning correlates are largely unknown. This cross‐sectional study investigates correlates of hypokinesia in HD and its effect on global functioning. Among 150 HD gene carriers, 96 patients were clinically motor manifest. Hypokinesia was assessed using the motor section of the Unified Huntington's Disease Rating Scale and global functioning was measured using the Total Functioning Capacity (TFC) scale. Neuropsychiatric measures included the Apathy Scale and the Composite International Diagnostic Interview for diagnosis of depression. The Mini Mental State Examination (MMSE) and a composite executive cognitive measure were used to assess global and executive cognitive functioning, respectively. Compared with 45 patients with no or mild hypokinesia, 51 patients with moderate to severe hypokinesia showed a significant difference in most clinical and neuropsychiatric variables and had worse cognitive functioning scores. However, using forward logistic regression analysis, poor executive cognitive functioning was the only independent correlate of hypokinesia (OR 7.33; 95% CI: 2.82–19.0; P < 0.001). Hypokinesia score was inversely associated with the TFC score (P < 0.001), also after adjusting for chorea, use of antipsychotics, apathy, and global and executive cognitive functioning. In conclusion, the presence of moderate to severe hypokinesia in HD patients co‐occurs with executive cognitive dysfunction and adversely affects global functioning. © 2010 Movement Disorder Society
High temperature causes masculinization of genetically female medaka by elevation of cortisol
Authors: Hayashi Yuki , Kobira Hiroshi , Yamaguchi Toshiya , Shiraishi Eri , Yazawa Takashi , Hirai Toshiaki , Kamei Yasuhiro , Kitano Takeshi
Published: May 2010

In poikilothermic vertebrates, sex determination is sometimes influenced by environmental factors such as temperature. However, little is known about the molecular mechanisms underlying environmental sex determination. The medaka (Oryzias latipes) is a teleost fish with an XX/XY sex determination system. Recently, it was reported that XX medaka can be sex‐reversed into phenotypic males by high water temperature (HT; 32–34°C) treatment during the sex differentiation period. Here we report that cortisol caused female‐to‐male sex reversal and that metyrapone (an inhibitor of cortisol synthesis) inhibited HT‐induced masculinization of XX medaka. HT treatment caused elevation of whole‐body levels of cortisol, while metyrapone suppressed the elevation by HT treatment during sexual differentiation. Moreover, cortisol and 33°C treatments inhibited female‐type proliferation of germ cells as well as expression of follicle‐stimulating hormone receptor (fshr) mRNA in XX medaka during sexual differentiation. These results strongly suggest that HT induces masculinization of XX medaka by elevation of cortisol level, which, in turn, causes suppression of germ cell proliferation and of fshr mRNA expression. Mol. Reprod. Dev. 77: 679–686, 2010. © 2010 Wiley‐Liss, Inc.
Reducing distortions in diffusion‐weighted echo planar imaging with a dual‐echo blip‐reversed sequence
Authors: Gallichan Daniel , Andersson Jesper L. R. , Jenkinson Mark , Robson Matthew D. , Miller Karla L.
Published: May 2010

The inherent distortions in echo‐planar imaging that arise due to inhomogeneities in the static magnetic field can lead to difficulties when attempting to obtain structurally accurate diffusion‐tensor imaging data. Parallel acceleration techniques can reduce the magnitude of these distortions but do not remove them entirely. Images can be corrected using a measured field map, but this is prone to error. One approach to correcting for these distortions, referred to here as “blip‐reversed” echo‐planar imaging, involves collecting a second set of images with the phase encoding reversed. Here, a novel approach to collecting blip‐reversed echo‐planar imaging data for diffusion‐tensor imaging is presented: a dual‐echo sequence is used in which the phase‐encoding direction of the second echo is swapped compared to the first echo. This allows benefits of the blip‐reversed approach to be exploited, with only a modest increase in scan time and, due to the extra data acquired, no significant loss of signal‐to‐noise efficiency. A novel approach to recombining blip‐reversed data is also presented, which involves refining the measured field map, using an algorithm to minimize the difference between the corrected images. The field map refinement is also applicable to conventionally acquired blip‐reversed sequences. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Noncompartmental kinetic analysis of DCE‐MRI data from malignant tumors: Application to glioblastoma treated with bevacizumab
Authors: Port Ruediger E. , Bernstein Lisa J. , Barboriak Daniel P. , Xu Lu , Roberts Timothy P. L. , van Bruggen Nicholas
Published: May 2010

Dynamic contrast enhanced MRI contrast agent kinetics in malignant tumors are typically complex, requiring multicompartment tumor models for adequate description. For consistent comparisons among tumors or among successive studies of the same tumor, we propose to estimate the total contrast agent–accessible volume fraction of tumor, including blood plasma, vpe, and an average transfer rate constant across all tumor compartments, Ktrans.av, by fitting a three‐compartment tumor model and then calculating the area under the tumor impulse‐response function (= vpe) and the ratio area under the tumor impulse response function over mean residence time in tumor (= Ktrans.av). If the duration of dynamic contrast enhanced MRI was too short to extrapolate the tumor impulse‐response function to infinity with any confidence, then conditional parameters v and Ktrans.av* should be calculated from the available incomplete impulse response function. Median decreases of 33% were found for both v and Ktrans.av* in glioblastoma patients (n = 16) 24 hours after the administration of bevacizumab (P < 0.001). Median total contrast‐enhancing tumor volume was reduced by 18% (P < 0.0001). The combined changes of tumor volume, v, and Ktrans.av* suggest a reduction of true vpe, possibly accompanied by a reduction of true Ktrans.av. The proposed method provides estimates of a scale and a shape parameter to describe contrast agent kinetics of varying complexity in a uniform way. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
The acellular matrix (ACM) for bladder tissue engineering: A quantitative magnetic resonance imaging study
Authors: Cheng Hai‐Ling Margaret , Loai Yasir , Beaumont Marine , Farhat Walid A.
Published: May 2010

Bladder acellular matrices (ACMs) derived from natural tissue are gaining increasing attention for their role in tissue engineering and regeneration. Unlike conventional scaffolds based on biodegradable polymers or gels, ACMs possess native biomechanical and many acquired biologic properties. Efforts to optimize ACM‐based scaffolds are ongoing and would be greatly assisted by a noninvasive means to characterize scaffold properties and monitor interaction with cells. MRI is well suited to this role, but research with MRI for scaffold characterization has been limited. This study presents initial results from quantitative MRI measurements for bladder ACM characterization and investigates the effects of incorporating hyaluronic acid, a natural biomaterial useful in tissue‐engineering and regeneration. Measured MR relaxation times (T1, T2) and diffusion coefficient were consistent with increased water uptake and glycosaminoglycan content observed on biochemistry in hyaluronic acid ACMs. Multicomponent MRI provided greater specificity, with diffusion data showing an acellular environment and T2 components distinguishing the separate effects of increased glycosaminoglycans and hydration. These results suggest that quantitative MRI may provide useful information on matrix composition and structure, which is valuable in guiding further development using bladder ACMs for organ regeneration and in strategies involving the use of hyaluronic acid. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Vessel‐encoded dynamic magnetic resonance angiography using arterial spin labeling
Authors: Okell Thomas W. , Chappell Michael A. , Woolrich Mark W. , Günther Matthias , Feinberg David A. , Jezzard Peter
Published: May 2010

A new noninvasive MRI method for vessel‐selective angiography is presented. The technique combines vessel‐encoded pseudocontinuous arterial spin labeling with a two‐dimensional dynamic angiographic readout and was used to image the cerebral arteries in healthy volunteers. Time‐of‐flight angiograms were also acquired prior to vessel‐selective dynamic angiography acquisitions in axial, coronal, and/or sagittal planes, using a 3‐T MRI scanner. The latter consisted of a vessel‐encoded pseudocontinuous arterial spin labeling pulse train of 300 or 1000 ms followed by a two‐dimensional thick‐slab flow‐compensated fast low‐angle shot readout combined with a segmented Look‐Locker sampling strategy (temporal resolution = 55 ms). Selective labeling was performed at the level of the neck to generate individual angiograms for both right and left internal carotid and vertebral arteries. Individual vessel angiograms were reconstructed using a bayesian inference method. The vessel‐selective dynamic angiograms obtained were consistent with the time‐of‐flight images, and the longer of the two vessel‐encoded pseudocontinuous arterial spin labeling pulse train durations tested (1000 ms) was found to give better distal vessel visibility. This technique provides highly selective angiograms quickly and noninvasively that could potentially be used in place of intra‐arterial x‐ray angiography for larger vessels. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Absence of a significant extravascular contribution to the skeletal muscle BOLD effect at 3 T
Authors: Sanchez Otto A. , Copenhaver Elizabeth A. , Elder Christopher P. , Damon Bruce M.
Published: May 2010

Blood oxygenation level dependent (BOLD) contrast in skeletal may reflect the contributions of both intravascular and extravascular relaxation effects. The purpose of this study was to determine the significance of the extravascular BOLD effect in skeletal muscle at 3 T. In experiments, R2* was measured before and during arterial occlusion under the following conditions: (1) the leg extended and rotated (to vary the capillary orientation with respect to the amplitude of static field) and (2) with the blood's signal nulled using a multiecho vascular space occupancy experiment. In the leg rotation protocol, 3 min of arterial occlusion decreased oxyhemoglobin saturation from 67% to 45% and increased R2* from 34.2 to 36.6 sec−1, but there was no difference in the R2* response to occlusion between the extended and rotated positions. Numerical simulations of intra‐ and extravascular BOLD effects corresponding to these conditions predicted that the intravascular BOLD contribution to the R2* change was always > 50 times larger than the extravascular BOLD contribution. Blood signal nulling eliminated the change in R2* caused by arterial occlusion. These data indicate that under these experimental conditions, the contribution of the extravascular BOLD effect to skeletal muscle R2* was too small to be practically important. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Factors related to self‐efficacy in persons with scleroderma
Authors: Buck Una , Poole Janet , Mendelson Cindy
Published: May 2010

Purpose: Scleroderma (SSc) is rare, and few studies have examined self‐efficacy in persons with the disease. Self‐efficacy is one precursor that has been shown to initiate changes in behaviour when managing chronic disease. The objective of this study was to explore the levels of self‐efficacy in persons with SSc, compare self‐efficacy in persons with limited or diffuse SSc and determine correlations between self‐efficacy, physical function and psychological variables.

Methods: Sixty‐two participants with SSc completed measures assessing self‐efficacy, depression, fatigue, pain, hand function and activity limitations. The mean age of participants was 52.9 years. The mean educational level was 15.8 years. Sixty‐seven per cent were married and 87.1% were women. Thirty participants had diffuse SSc, 27 had limited SSc and five were unclassified.

Results: The only significant differences between the two disease subtypes were in hand function and self‐efficacy function subscale scores. Total self‐efficacy scores significantly correlated with marital status, employment, self‐reported health, depression, functional ability, fatigue, pain and hand function. Similarly, self‐efficacy function scale scores correlated significantly with employment, self‐reported health, functional ability, pain and hand function. Self‐efficacy pain scale scores correlated significantly with fatigability. The self‐efficacy other scale scores correlated significantly with depression and fatigability. Participants with higher levels of pain and depression, more fatigue, more general disability and more hand disability had lower self‐efficacy.

Conclusion: Self‐efficacy correlates with physical function and psychological variables, and could predict how patients manage their health. Self‐efficacy may increase through participation in educational programmes focusing on self‐management of these variables. Copyright © 2010 John Wiley & Sons, Ltd.
Can the application of control theory assist patient management in rheumatoid arthritis?
Authors: Mann Cindy
Published: May 2010

Supporting patient self‐management is an important part of the care of patients with rheumatoid arthritis (RA) but patients vary in their capacity and willingness to manage their illness and may feel overwhelmed by the challenge of controlling the impact on their life. This paper discusses the value and importance of control theory and how it might be applied to enhance patients' self‐management. Not only does it offer a means of identifying those who might have greatest difficulty in managing their illness, but it also points the way to effective interventions. Copyright © 2010 John Wiley & Sons, Ltd.
Monitoring disease progression using high‐density motor unit number estimation in amyotrophic lateral sclerosis
Authors: van Dijk Johannes P. , Schelhaas Helenius J. , Van Schaik Ivo N. , Janssen Henny M.H.A. , Stegeman Dick F. , Zwarts Machiel J.
Published: May 2010

In amyotrophic lateral sclerosis (ALS), progressive motor neuron loss causes severe weakness. Functional measurements tend to underestimate the underlying pathology because of collateral reinnervation. A more direct marker of lower motor neuron loss is of significant importance. We evaluated high‐density motor unit number estimation (MUNE), as compared with the ALS Functional Rating Scale (ALSFRS) and maximal compound muscle action potential (CMAP) amplitude, for monitoring and classifying disease progression. MUNE showed good reproducibility (intraclass correlation coefficient = 0.86). MUNE showed a significantly greater decrease than the ALSFRS, the Medical Research Council (MRC) scale, and CMAP amplitude. Patients could be stratified into groups with rapidly or slowly progressive disease based on a decrement in MUNE at 4 months from baseline; ALSFRS score at 8 months was significantly lower in the rapidly progressive group. MUNE was sensitive to motor neuron loss early in the disease course when compared to other clinical measures. Stratification of patients based on a decrease in MUNE seems feasible. Muscle Nerve, 2010
Nonsurgical transurethral collagen denaturation for stress urinary incontinence in women: 18‐month results from a prospective long‐term study
Authors: Elser Denise M. , Mitchell Gretchen K. , Miklos John R. , Nickell Kevin G. , Cline Kevin , Winkler Harvey , Wells W. Glen
Published: May 2010

Aims

To evaluate 18‐month safety and durability of efficacy of nonsurgical transurethral collagen denaturation as treatment for stress urinary incontinence (SUI) in women.

Methods

Study comprised women with SUI due to bladder outlet hypermobility for at least 12 months who failed conservative treatment and had not undergone surgery or bulking agent treatment. This one‐time procedure was performed in a physician's office or ambulatory treatment center. Patients kept voiding diaries and completed the Incontinence Quality of Life (I‐QOL), Urogenital Distress Inventory (UDI‐6), and Patient Global Impression of Improvement measures at baseline and at 3, 6, 12, and 18 months posttreatment.

Results

At 18 months, intent‐to‐treat analysis revealed that patients experienced significant reductions in the median number of stress leaks daily (0.43; P < 0.006) and weekly (3.0; P < 0.006) versus baseline, with 46.7% reporting a 50% or greater reduction in leakage. Mean I‐QOL score improved 10.9 points (median 8.5; P < 0.0001), with 47.8% having a 10‐point or greater improvement and 50.4% reporting improved symptoms versus baseline. Mean UDI‐6 improvement was 13.0 points, with a stress incontinence subscore improvement of 17.0 points. Overall, 47.0% of patients were “somewhat” or “very” satisfied, and 52.9% would recommend the procedure to a friend. The procedure was shown to be safe and effective, with no new treatment‐related adverse events reported at 18 months.

Conclusions

Transurethral collagen denaturation resulted in significant improvements in stress leaks and quality of life for at least 18 months. This procedure offers a safe, effective, nonsurgical treatment option for women with SUI. Neurourol. Urodynam. 29:1424–1428, 2010. © 2010 Wiley‐Liss, Inc.
Evaluating the use of different waveforms for intravesical electrical stimulation: A study in the rat
Authors: De Bock Filip , Dirckx Joris , Wyndaele Jean‐Jacques
Published: May 2010

Aim

For decades, monophasic square wave pulses have been used for intravesical electrical stimulation (IVES) in diagnosis and treatment of lower urinary tract dysfunction. The use of other waveforms, more preferred by patients or more effective for neural stimulation, has hardly been studied before. This study compares the effect of several waveforms and derived parameters in IVES.

Methods

IVES, performed in eight female Sprague–Dawley rats, was given for 300 sec with constant frequency (10 Hz) and current amplitude (6 mA) with unipolar square, biphasic square, asymmetric biphasic square, double square, unipolar exponential rise, biphasic exponential rise, and double‐exponential rise wavepulses with different pulse durations (2 × 5 msec, 20 msec, or 2 × 20 msec). Bladder pressure was recorded. Average current and average power were calculated.

Results

Stimulations with the different waveforms resulted in the same maximal pressure rise (all P > 0.1). The average charge was zero for biphasic waveforms. For exponential rise pulse waveforms the total injected charge was lower than that for the monophasic square pulse waveform. The average power was the highest for biphasic waveforms and the lowest for monophasic double‐exponential rise pulses waveform.

Conclusions

Charge‐balanced waveforms, which are more preferred by patients, are equally effective in evoking IVES‐induced detrusor contraction as monophasic square pulse waveforms. Thus, it can be beneficial in clinical practice to replace the monophasic square pulse waveform for IVES by charge‐balanced waveforms. Furthermore, the stimulation power and thus the requested energy can be reduced by changing the waveform. This can be important for electrical stimulation using implanted batteries. Neurourol. Urodyn. 30:169–173, 2011. © 2010 Wiley‐Liss, Inc.
Max–min utility fair flow management for networks with route diversity
Authors: Rubin Izhak , Zhang Runhe
Published: May 2010

A regional central manager is employed to set aside, for the regional (or back‐bone) network that it manages, for each flow class, communications capacity resources for a specific future time horizon. In the context of such a traffic management operation, a longer temporal scale is involved in controlling the admission and distribution of flows across the network. For management scal‐ability purposes, flows are aggregated into flow classes. Furthermore, we consider a network operation under which multiple simultaneously activated routes are employed, across possibly distinct segments, to distribute traffic between identified source–destination pairs. We aim to ensure that the utility assigned to each class is as high as feasibly possible while striving to raise the utility gained by all classes in a max–min fair manner. In doing so, we incorporate the communications capacity constraints that are imposed by the underlying hybrid of directional and/or multiple‐access wireline and wireless communications media employed across the network system. We develop and present in this paper an optimal algorithm for solving such a traffic management problem. It yields multi‐utility‐based max–min fair distributions of flow rates, per each class, across the specified multitude of simultaneously activated multi‐segment routes. To guarantee that admitted flows are granted their desired capacity resources (and targeted corresponding utility levels), the selection of optimal flow distributions across the network routes is combined with the use of a flow admission control scheme that serves to optimally limit the aggregate rate of flows admitted for each flow class. As illustrative examples, we demonstrate the effectiveness of our solution in comparing its performance with that obtained under the use of a traffic regulation scheme that is not overlaid with a traffic management mechanism that serves to set aside resources for the support of flow classes. We also illustrate the use of our optimal algorithm for determining the optimal placement of unmanned aerial vehicle platforms that serve to supplement a terrestrial transport segment with a space‐based one. Copyright © 2010 John Wiley & Sons, Ltd.
Three‐dimensional modelling and simulation of magnetorheological fluids
Authors: Han K. , Feng Y. T. , Owen D. R. J.
Published: May 2010

A magnetorheological fluid (MR fluid) is a type of smart fluid composed of micrometer‐sized magnetizable particles suspended in a carrier fluid. The rheological properties of an MR fluid can be greatly altered upon application of an external magnetic field. This paper presents a computational framework for the numerical study of MR fluids, in which a two‐stage modelling and simulation strategy is proposed to achieve reasonable accuracy and computational efficiency. At the first stage for simulating the particle chain formation, the particle dynamics plays a major role whereas the hydrodynamics of the fluid flow is of secondary importance. Thus an MR fluid is modelled in the context of the discrete element method and the simple Stokes formula is adopted for the hydrodynamic interaction. At the second stage, the formulated particle chains are applied as the initial configuration for simulating the rheological properties of the fluid under different shear loading conditions. A combined lattice Boltzmann and discrete element approach is employed to fully resolve the fluid field and the hydrodynamic interactions between the fluid and the particles. Some relevant magnetic models are comprehensively reviewed and the mutual dipole model is employed in this work to account for the magnetic interactions between the particles. The proposed solution procedure is illustrated via a set of numerical simulations for a representative volume element of an MR fluid. Copyright © 2010 John Wiley & Sons, Ltd.
A theoretical study on the smoothed FEM (S‐FEM) models: Properties, accuracy and convergence rates
Authors: Liu G. R. , Nguyen‐Xuan H. , Nguyen‐Thoi T.
Published: May 2010

Incorporating the strain smoothing technique of meshfree methods into the standard finite element method (FEM), Liu et al. have recently proposed a series of smoothed finite element methods (S‐FEM) for solid mechanics problems. In these S‐FEM models, the compatible strain fields are smoothed based on smoothing domains associated with entities of elements such as elements, nodes, edges or faces, and the smoothed Galerkin weak form based on these smoothing domains is then applied to compute the system stiffness matrix. We present in this paper a general and rigorous theoretical framework to show properties, accuracy and convergence rates of the S‐FEM models. First, an assumed strain field derived from the Hellinger–Reissner variational principle is shown to be identical to the smoothed strain field used in the S‐FEM models. We then define a smoothing projection operator to modify the compatible strain field and show a set of properties. We next establish a general error bound of the S‐FEM models. Some numerical examples are given to verify the theoretical properties established. Copyright © 2010 John Wiley & Sons, Ltd.
Governments demand compliance, ethics demands leadership
Authors: Lager James M.
Published: May 2010

Governments are imposing new rules and restrictions on businesses and their leaders in the wake of the recent economic crisis, attempting to address the regulatory failure and corporate avarice frequently blamed for the global recession. The ever‐present incentive for leaders to show profitability, coupled with the inability of governments or private industry to support continuous controls or monitoring, condemns these new rules, restrictions, and enforcement mechanisms to relative ineffectiveness.

Scandal can ruin an organization and a leader's reputation, and cosmetic or even actual compliance with new rules and restrictions will not always insulate corporate harm from unethical conduct. This article suggests that a leader wishing to avoid fines or business failure should prevent abusive or improper business conduct not by adoption of codes of conduct and periodic rules‐based ethics training, but by establishing and maintaining a values‐based organizational culture supportive of ethical behaviour, largely through the principles of ethical leadership.

Copyright © 2010 John Wiley & Sons, Ltd.
Eosinophilia and multifocal vertebral involvement with Hodgkin lymphoma
Authors: Küpeli Serhan , Kara Fehime , Akyüz Canan , Büyükpamukçu Münevver
Published: May 2010

Patients with Hodgkin lymphoma (HL) usually present with lymphadenopathies. Osseous involvement at presentation is extremely rare. Occurrence of both eosinophilia and osseous involvement has not been reported frequently. We present an adolescent female complaining of lower back pain for 6 months, in whom, multifocal vertebral involvement and peripheral blood eosinophilia preceded the final diagnosis of HL. Pediatr Blood Cancer. 2010;55:560–561. © 2010 Wiley‐Liss, Inc.
Autologous stem cell transplantation as treatment modality in a patient with relapsed pancreatoblastoma
Authors: Hamidieh Amir Ali , Jalili Mahdi , Khojasteh Omid , Ghavamzadeh Ardeshir
Published: May 2010

Pancreatoblastoma (PB) is a rare malignant neoplasm of the pancreas, which occurs mostly during childhood. Presently, the optimal treatment strategy is neither clear nor uniform for patients in advanced stages, in particular those with metastasis, inoperable, or recurrent tumors. To our knowledge, until now, only one patient with PB has been treated with hematopoietic stem cell transplantation (HSCT) following aggressive chemotherapy and surgical resection. Here we report the second case of PB who was treated with aggressive chemotherapy combined with autologous peripheral blood stem cell transplantation. Pediatr Blood Cancer. 2010;55:573–576. © 2010 Wiley‐Liss, Inc.
A phase II trial and pharmacokinetic study of oxaliplatin in children with refractory solid tumors: A Children's Oncology Group study
Authors: Beaty Orren , Berg Stacey , Blaney Susan , Malogolowkin Marcio , Krailo Mark , Knight Ronald , Schaiquevich Paula , Stewart Clinton , Chen Zhengjia , Nelson Marvin , Voss Stephan , Ivy S. Percy , Adamson Peter C.
Published: May 2010

Background

Platinating agents are used in the treatment of a spectrum of childhood cancers. Oxaliplatin, a third generation platinum compound, may provide less toxicity and be more effective. A phase 2 study was performed to estimate the response rate to single agent oxaliplatin in patients with refractory pediatric solid tumors, and to further describe the toxicities and pharmacokinetics of the drug in this population.

Patients and Methods

Subjects, ≤21 years of age at original diagnosis, received oxaliplatin (130 mg/m2) intravenously every 21 days. Prior platinum exposure was acceptable. Histologies included: Ewing sarcoma/peripheral PNET, osteosarcoma, rhabdomyosarcoma, neuroblastoma, high and low grade astrocytoma, brain stem glioma, ependymoma, hepatoblastoma and selected rare tumors. A two‐stage design, enrolling 10 + 10 subjects, was used for each disease stratum. Limited sampling pharmacokinetic studies were performed.

Results

Of 124 eligible subjects (75 males), 113 were evaluable for response and 69 (62%) had received platinum previously. Only one objective response was observed, a partial response in a 6‐year‐old child with ependymoma. An additional 13 subjects with various other solid tumors had stable disease, receiving a median (range) of 13.5 (2–17) cycles. Five subjects completed 17 treatment cycles. Thrombocytopenia was the most common toxicity observed. The median (range) terminal half‐life and clearance for ultrafiltrable platinum were 293 (187–662 hr) and 14.0 (1.9–24.9 L/hr/m2), respectively (n = 49).

Conclusions

Although reasonably well tolerated, oxaliplatin administered as a single agent has limited activity in pediatric patients with relapsed or refractory solid tumors. Pediatr Blood Cancer. 2010;55:440–445. © 2010 Wiley‐Liss, Inc.
Being a messenger of life‐threatening conditions: Experiences of pediatric oncologists
Authors: Stenmarker Margaretha , Hallberg Ulrika , Palmérus Kerstin , Márky Ildikó
Published: May 2010

Background

A nationwide population‐based study with questionnaires involving 90 pediatric oncologists was performed in Sweden in 2006/2007. On the basis of this quantitative study, a qualitative study was performed. The aim of this qualitative study was to focus on the main concern of these physicians facing malignant disorders, psychosocial issues, and existential provocation. Furthermore, the strategies for handling these challenges were also studied.

Method

Interviews were conducted in 2007 with ten physicians of both genders, with more than 10 years' experience, who were active and previously active in pediatric oncology, and were working at academic and non‐academic medical centers. The interviews were analyzed according to the inductive general research method of classical grounded theory. Every oncologist was selected from the nationwide study.

Results

A core category, that is, their main concern, labeled being a messenger of life‐threatening conditions, was identified. To manage this difficult task of acting like a messenger breaking bad news, five handling categories were used: obtaining knowledge and information, saving one's strength and resources, building a close relationship, avoiding identification, and dealing with one's attitude to central life issues. All the categories and strategies used are described in the text.

Conclusions

The challenge of making difficult decisions and delivering difficult news is an inevitable part of the patient–physician relationship in pediatric oncology. This qualitative study highlights the psychological aspects of being a pediatric oncologist. The study presents some practical implications in the daily work and physician‐related recommendations on how to overcome the demanding role of messenger. Pediatr Blood Cancer. 2010;55:478–484. © 2010 Wiley‐Liss, Inc.
Initial lymphocyte count and the development of persistent/chronic immune thrombocytopenic purpura
Authors: Ahmed Ibrahim , Rajpurkar Madhvi , Thomas Ronald , Chitlur Meera
Published: May 2010

Background

Acute immune thrombocytopenic purpura (ITP) is a common, benign, self‐limiting disease in children. Chronic ITP is diagnosed when thorombocytopenia persists beyond 12 months. Older age is associated with increased risk for development of chronic ITP. The main objective of the current study was to examine whether total leukocyte (TLC) and absolute lymphocyte counts (ALC) at diagnosis correlate with the persistence of ITP beyond 6 months.

Procedure

Two hundred and twenty four consecutive medical records for patients diagnosed with immune thrombocytopenia, between April 1993 and July 2007, were reviewed and 188 patients were eligible for analysis. Case records were examined to ascertain the following information: age, gender, ethnicity, date of presentation, presenting CBC with differential count, treatment given and the outcome.

Results

The male to female ratio was almost 1:1; 24% (45/188) of patients had persistent ITP beyond 6 months. We determined that age >8.5 year, TLC < 6,250/µl and ALC < 3,050/µl was associated with a significant risk for development of persistent ITP beyond 6 months.

Conclusions

TLC and ALC at diagnosis are predictive variables for the development of persistent/chronic ITP. Further studies are recommended to confirm the current finding and to assess the underlying pathophysiology with the course of the ITP. Pediatr Blood Cancer. 2010;55:508–511. © 2010 Wiley‐Liss, Inc.
SBDS protein expression patterns in the bone marrow
Authors: Wong Trisha E. , Calicchio Monica L. , Fleming Mark D. , Shimamura Akiko , Harris Marian H.
Published: May 2010

Shwachman–Diamond syndrome (SDS) is an inherited bone marrow failure syndrome caused by biallelic SBDS gene mutations. Here we examined SBDS protein levels in human bone marrow. SBDS protein expression was high in neutrophil progenitors, megakaryocytes, plasma cells, and osteoblasts. In contrast, SBDS protein levels were low in all hematopoietic cell lineages from patients harboring the common SBDS mutations. We conclude that SBDS protein levels vary widely between specific marrow lineages. Uniformly low SBDS protein expression levels distinguish the majority of SDS patients from controls or other marrow failure syndromes. Pediatr Blood Cancer. 2010;55:546–549. © 2010 Wiley‐Liss, Inc.
Outcome for children treated for relapsed or refractory acute myelogenous leukemia (rAML): A therapeutic advances in childhood leukemia (TACL) consortium study
Authors: Gorman Matthew F. , Ji Lingyun , Ko Richard H. , Barnette Phillip , Bostrom Bruce , Hutchinson Raymond , Raetz Elizabeth , Seibel Nita L. , Twist Clare J. , Eckroth Elena , Sposto Richard , Gaynon Paul S. , Loh Mignon L.
Published: May 2010

Background

Current event‐free survival (EFS) rates for children with newly diagnosed acute myeloid leukemia (AML) approach 50–60%. We hypothesize that further improvements in survival are unlikely to be achieved with traditional approaches such as dose intensive chemotherapy or hematopoietic stem cell transplants, since these therapies have been rigorously explored in clinical trials. This report highlights efforts to assess the response rates and survival outcomes after first or greater relapse in children with AML.

Procedure

We performed a retrospective cohort review of pediatric patients with relapsed and refractory AML (rAML) previously treated at TACL institutions between the years of 1995 and 2004. Data regarding disease characteristics at diagnosis and relapse, treatment response, and survival was collected on 99 patients and 164 medullary relapses or treatment failures.

Results

The complete response (CR) rate following the second therapeutic attempt was 56 ± 5%. CR rates following a third treatment attempt was 25 ± 8% while 17 ± 7% achieved CR following the fourth through sixth treatments. The 5‐year disease‐free survival in patients achieving CR following a second therapeutic attempt was 43 ± 7%. The 5‐year EFS and overall survival (OS) rates for all patients receiving a second treatment attempt was 24 ± 5% and 29 ± 5%, respectively.

Conclusions

This CR rate following a second therapeutic attempt and OS rate in patients with rAML is consistent with the literature. There are limited published data of CR rates for subsequent relapses. Our data can serve as a historical benchmark to compare outcomes of future therapeutic trials in rAML against traditional chemotherapy regimens. Pediatr Blood Cancer. 2010;55:421–429. © 2010 Wiley‐Liss, Inc.
Spontaneous resolution of Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis
Authors: Belyea Brian , Hinson Ashley , Moran Cassandra , Hwang Eugene , Heath Jessica , Barfield Raymond
Published: May 2010

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a reactive, proliferative disorder of the immune system resulting in lymphohistiocytic proliferation, hemophagocytosis, and cytokine dysregulation. The most common infectious trigger in sHLH is Epstein–Barr virus (EBV‐HLH). Current treatment protocols for EBV‐HLH have a cure rate of approximately 75%; however, there are significant toxicities associated with these therapies. We present two patients with EBV‐HLH who experienced spontaneous resolution of their disease prior to the initiation of therapy, suggesting there may be a subgroup of patients with EBV‐HLH who do well with conservative management and can avoid potentially toxic therapies. Pediatr Blood Cancer. 2010;55:754–756. © 2010 Wiley‐Liss, Inc.
Effect of deformation on knitted glass preform in‐plane permeability
Authors: Dusserre Gilles , Jourdain Eric , Bernhart Gérard
Published: May 2010

The excellent processing properties of knitted preforms for composite applications, as formability and permeability, are not sufficient to compensate the poor mechanical characteristics of the resulting material. Initial preform deformation is a way to improve these properties, but it modifies the permeability and changes the optimal infiltration conditions. This article presents an experimental setup and discusses the reliability of the permeability measurements. Experimental results show that the course‐wise permeability is significantly modified by the deformation of the fabric, whereas the wale‐wise permeability is quite insensitive to the deformation. In an equivalent isotropic system, the deformation essentially influences the anisotropy ratio. POLYM. COMPOS., 32:18–28, 2011. © 2010 Society of Plastics Engineers
Resistive viscoelasticity of silicone rubber/carbon black composite
Authors: Wang Shouli , Wang Peng , Ding Tianhuai
Published: May 2010

Electrical conductive polymer composites are shown as prospective flexible pressure and stretch sensors for detecting the dangerous deformations and for sensing the pressure with minimal intrusion. To better understand the piezoresistive mechanism and improve the performance of this type of sensor, a series of experiments were conducted to investigate the resistive viscoelasticity of silicone rubber/carbon black composite film. First, the flexible conductive composite film was composed with liquid silicone rubber as the matrix and conductive carbon black as the filler. The filler loading was fixed at 5 phr in mass ratio. Then, the resistive viscoelasticity of the composite film was studied as a function of frequency in the range from DC to 1 MHz, including resistive creep, resistive relaxation, and resistive recovery, although in a standard experiment, one‐step stress or one‐step strain was loaded in transient time and the resistance responses were measured. Result from the experiment shows that the creep of resistance is composed of two distinct segments. One is coincident with the strain creep of a typical viscoelastic material, while the other is quite different. Both the relaxation and the recovery of resistance exhibit strong frequency dependence. The relaxation speed becomes slower with the increase of exciting frequency except DC, and the relaxation speed is marginal when excited by DC electrical field. The recovery time becomes shorter with the increase of the exciting frequency. POLYM. COMPOS., 32:29–35, 2011. © 2010 Society of Plastics Engineers
Rheological properties of poly(acrylonitrile‐co‐methyl acrylate)/clay nanocomposites prepared via emulsion polymerization
Authors: Zengeni Eddson , Hartmann Patrice C. , Sanderson Ronald D.
Published: May 2010

Poly(acrylonitrile‐co‐methyl acrylate)/clay nanocomposites were prepared by free radical polymerization in emulsion using 2‐acrylamido‐2‐methyl‐1‐propanesulphonic acid (AMPS) as a compatibilizer. The resultant nanocomposites were of partially exfoliated morphology despite the variations in clay content among the nanocomposites, as confirmed by transmission electron microscopy and small‐angle X‐ray scattering analysis. Rheological studies of these materials were carried out using parallel plate geometry. The storage modulus increased monotonically with increasing clay content throughout the frequency range studied. However, the neat copolymer, poly(acrylonitrile‐co‐methyl acrylate) and its nanocomposites, exhibited long relaxation behavior as the storage modulus (G′) was greater than the loss modulus (G″) throughout the angular frequency range studied. The complex viscosity of the nanocomposites increased with increasing clay content and they exhibited shear‐thinning behavior. Despite the enhanced rheological properties observed, the copolymer and its nanocomposites underwent structural changes during oscillatory measurements due to cyclization reactions. POLYM. COMPOS., 32:59–66, 2011. © 2010 Society of Plastics Engineers
Selective intrauterine growth restriction in monochorionic diamniotic twin pregnancies
Authors: Valsky Dan V. , Eixarch Elisenda , Martinez Josep Maria , Gratacós Eduard
Published: May 2010

Selective intrauterine growth restriction (sIUGR) occurs in 10 to 15% of monochorionic (MC) twins, and it is associated with a substantial increase in perinatal mortality and morbidity. Clinical evolution is largely influenced by the existence of intertwin placental anastomoses: pregnancies with similar degrees of fetal weight discordance are associated with remarkable differences in clinical behavior and outcome. We have proposed a classification of sIUGR into three types according to umbilical artery (UA) Doppler findings (I‐normal, II‐absent/reverse end‐diastolic flow, III‐intermittent absent/reverse end‐diastolic flow), which correlates with distinct clinical behavior, placental features and may assist in counseling and management. In terms of prognosis, sIUGR can roughly be divided in two groups: type I cases, with a fairly good outcome, and types II and III, with a substantial risk for a poor outcome. Management of types II and III may consist in expectant management until deterioration of the IUGR fetus is observed, with the option of cord occlusion if this occurs before viability. Alternatively, active management can be considered electively, including cord occlusion or laser coagulation. Both therapies seem to increase the chances of intact survival of the larger fetus, while they entail, or increase the chances of, intrauterine demise of the IUGR fetus. Copyright © 2010 John Wiley & Sons, Ltd.
Quantification and application of the placental epigenetic signature of the RASSF1A gene in maternal plasma
Authors: Zhao Fuxi , Wang Jian , Liu Runhua , Yang Jing , Cui Ke , Wu Yongming , Guo Juncheng , Mu Yaqin , Wang Xiying
Published: May 2010

Objectives

The aims of the detection of hypermethylated RASSF1A gene in maternal plasma from all three trimesters of pregnancy were to show its feature of cell‐free fetal DNA and to make up deficients of genetic markers. This study also aimed at investigating of its application value in pre‐eclampsia compared with third trimester.

Methods

Eighty pregnant women (7–41 gestational weeks) including normal pregnant women (60 cases) and pre‐eclamptic pregnant women (20 cases) were selected as study groups and 20 normal non‐pregnant women were selected as control group. Free DNA of plasma samples was extracted, and RASSF1A levels before and after double‐methylation‐sensitive restriction enzyme digestion of HinP1I and HhaI were determined to measure total and fetal cell‐free DNA, respectively. β‐Actin gene was detected as a control to confirm complete enzyme digestion.

Results

The median concentrations of hypermethylated RASSF1A gene were 46 copies/mL in first trimester, 96 copies/mL in second trimester, 527 copies/mL in third trimester and 1947 copies/mL in pre‐eclampsia. There was positive correlation between fetal‐derived hypermethylated RASSF1A levels and the severity of pre‐eclampsia.

Conclusion

Hypermethylated RASSF1A gene may be considered as an epigenetic marker to detect the fetal DNA in maternal plasma and expands the clinical application of non‐invasive prenatal diagnosis. Copyright © 2010 John Wiley & Sons, Ltd.