bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of intracellular diffusion in normal and globally‐ischemic rat brain via 133Cs NMR
Authors: Neil Jeffrey J. , Duong Timothy Q. , Ackerman Joseph J. H.
Published: February 2011

The question of whether the apparent diffusion coefficient (ADC) of intracellular water changes after brain injury was addressed by using 133Cs as an indicator to report on the state of the intracellular environment. Cesium is an NMR‐detect‐able potassium analog that accumulates in the intracellular space and is detectable in rat brain after being added to the animal's diet. The ADC of cesium was measured before and after the death of the rat. The cesium ADC fell from 0.91 ± 0.05 × 10−3 mm2/s (mean ± SEM, n = 5) in the alive rat to 0.71 ± 0.05 × 10−3 mm2/s within 20 min (the best time resolution of the experiment) of the death of the animal and stayed at this value for at least 3 h (P < 0.001). Assuming that the ADC of cesium reflects motion in the intracellular environment, these results support the idea that there are changes associated with cell injury that would cause a reduction in the ADC of intracellular water. Hence, one factor contributing to the decrease in water ADC after brain injury is a change in the ADC of intracellular water.
Evaluation of triple‐quantum‐filtered 23Na NMR in monitoring of intracellular na content in the perfused rat heart: Comparison of intra‐ and extracellular transverse relaxation and spectral amplitudes
Authors: Dizon José M. , Tauskela Joseph S. , Wise David , Burkhoff Daniel , Cannon Paul J. , Katz José
Published: February 2011

Multiple‐quantum filtered (MQF) NMR offers the possibility of monitoring intracellular (IC) Na content in the absence of shift reagents (SR), provided that (i) the contribution from IC Na to the MQF spectrum is substantial and responds to a change in IC Na content, and (ii) the amplitude of the extracellular (EC) MQF component remains constant during a change in IC Na content. The validity and basis for these conditions were examined in isolated perfused rat hearts using SR‐aided and SR‐free triple‐quantum filtered (TQF) 23NaNMR. Despite a myocardial Na content that was only ˜1/70 that of EC Na. IC Na contributed to over 25% of the total TQF spectrum acquired in the absence of SR. Transverse relaxation times (T2) were approximately twice as long for EC compared to IC Na, despite SR‐induced relaxation of T2 for the former pool. However, the efficiency of generation of the TQF signal was similar for IC and EC Na, indicating that a much greater percentage of IC relative to EC Na exhibits TQ coherence. During constant perfusion with ouabain (0.2 mM for 25 min) or with a hypoxic and aglycemic solution (50 min), the amplitude of the IC TQF spectrum increased by ˜330% and ˜280%, respectively. In contrast, the amplitude of the EC TQF spectra remained essentially constant for both interventions. The amplitude for IC Na increased ˜250% relative to baseline during no‐flow ischemia (60 min), whereas the amplitude of the EC TQF spectra decreased by ˜33% before stabilizing. In SR‐free experiments, the TQF spectral amplitude increased ˜2‐fold during the constant perfusion interventions, but did not change significantly during no‐flow ischemia. These data suggest that the change in the TQF spectral amplitude during constant perfusion interventions is from IC Na, and that TQF techniques in the absence of SR may be useful in monitoring IC Na during these interventions. The fall in the amplitude of the EC TQF spectral amplitude during no‐flow ischemia complicates the use of TQF techniques without SR during this intervention.
Noninvasive temperature measurement in Vivo using a temperature‐sensitive lanthanide complex and 1H magnetic resonance spectroscopy
Authors: Frenzel Thomas , Roth Klaus , Koßler Susanne , Radüchel Bernd , Bauer Hans , Platzek Johannes , Weinmann Hanns‐Joachim
Published: February 2011

A new lanthanide complex, praseodymium‐2‐methoxyethyl‐DO3A, was tested as a temperature indicator for 1H magnetic resonance spectroscopy under in vivo conditions, using a 2‐T imaging system. The chemical shift of the methoxy group of the compound is strongly temperature dependent. In vitro, a shift change of −0.131 ppm/°C was found. The signal was shifted by about −24 ppm relative to the water signal, allowing easy water suppression and signal identification in vivo. The body temperatures of eight anesthetized rats were measured in the liver after intravenous administration of 1 mmol/kg of the praseodymium complex under different heating conditions of the animal. The temperatures calculated from the spectra were in good agreement (deviation < ± 1°C) with values obtained simultaneously with a thermocouple placed in the rectum of the animals.
Phase‐Encode reordering to minimize errors caused by motion
Authors: MacGowan Christopher K. , Wood Michael L.
Published: February 2011

A new method for suppressing the effects of motion in MR images by reordering the acquisition of k space has been developed. Existing reordering methods suffer from image blurring. The method presented here applies specifically to translation along the phase‐encoding direction, in which case it reduces both ghosting and blurring. The method is conceptually similar to a linear phase shift of k space, except that it has the advantage of not corrupting stationary structures inadvertently. The method is intended for anatomic sites in which substantial translational motion occurs along the phase‐encoding direction, such as the cranial‐caudal motion of the liver and kidneys. The reordering method is motivated from an analysis of factors affecting the severity of motion artifacts. The theory behind the reordering method is described and validated experimentally by imaging a moving phantom.
Transesophageal cardiac pacing during magnetic resonance imaging: Feasibility and safety considerations
Authors: Hofman Mark B. M. , de Cock Carel C. , van der Linden Johannes C. , van Rossum Albert C. , Visser Frans C. , Sprenger M. , Westerhof N.
Published: February 2011

The feasibility and safety of transesophageal cardiac pacing during clinical MRI at 1.5 Tesla is considered. An MRI compatible pace catheter was developed. In vitro testing showed a normal performance of the pulse generator, image artifacts that extended less than 11 mm from the catheter, and a less than 5% increase in noise. Cardiac stimulation induced by MRI was not observed and, theoretically, is not expected. Potentially, tissue around the catheter tip may become heated. This heating (ΔT) was monitored. Eight dogs were exposed to MRI during pacing. For low RF radiation exposure, a time‐averaged squared B1 field below 0.08 pT2 (SAR < 0.03 W/kg), ΔT was below 1°C. For high RF radiation exposure, but at normal RF radiation specific absorption rate (0.4 W/kg), ΔT was 5°C. Thus, transesophageal atrial pacing during MRI at low RF exposure seems to be possible to perform cardiac stress studies or to correct unstable heart rates.
A method for generating magnetic resonance microimaging T2 maps with low sensitivity to diffusion
Authors: Mlynárik Vladimír , Degrassi Anna , Toffanin Renato , Jarh Orest , Vittur Franco
Published: February 2011

Generating T2 maps in magnetic resonance microimaging is often complicated by the self‐diffusion of water molecules. A modification of the standard spin‐echo pulse sequence is proposed which minimizes this effect. Experiments with doped water confirmed that the T2 values obtained with the modified sequence were equal within the experimental error to the value obtained by the spectroscopic Carr‐Purcell‐Meiboom‐Gill method. The applicability of the technique is demonstrated by generating T2 maps of porcine articular cartilage. Key words: MR microimaging; relaxation; diffusion; cartilage.
Frequency resolved single‐shot MR imaging using stochastic k‐space trajectories
Authors: Scheffler Klaus , Hennig Jürgen
Published: February 2011

A new single‐shot stochastic imaging technique with a random k‐space path that provides very selective filtering with respect to chemical shift or off‐resonance signals of the investigated tissue is proposed. It is demonstrated that in stochastic imaging only on‐resonance compartments are visible whereas frequency shifted compartments cancel to noise that is distributed over the whole image. This method can be used as a single‐shot chemical shift selective imaging technique and allows to calculate frequency resolved spectra for each spatial position of the image based on a single signal aquisition. The single‐shot stochastic imaging sequence makes high demands on the gradient system and the theoretical k‐space trajectory is distorted by imperfect gradient performance. Therefore an additional k‐space guided imaging technique that uses the true, measured k‐space trajectory to correct artifacts generated by eddy currents and delay times of the rapid switched gradients is presented. In vitro and in vivo measurements demonstrate the successful implementation of single‐shot stochastic imaging on a conventional MR scanner with unshielded gradient systems.
Intensity correction of phased‐array surface coil images
Authors: Murakami James W. , Hayes Cecil E. , Weinberger Ed
Published: February 2011

Phased‐array coils distribute the high signal‐to‐noise ratio (SNR) performance of their small component surface coils over the larger area covered by the entire array. The inhomogeneous sensitivity profiles of the component surface coils result in images with very high signal near the phased‐array and decreased signal far from the array. This paper presents a postprocessing algorithm for correcting these coil‐related intensity variations. The algorithm's performance was evaluated by correcting images of volunteers acquired with several different receive‐only phased‐array surface coils.
Reproducibility of high spatial resolution proton magnetic resonance spectroscopic imaging in the human brain
Authors: Charles H. Cecil , Lazeyras François , Tupler Larry A. , Krishnan K. Ranga R.
Published: February 2011

The application of proton (1H) magnetic resonance spectroscopic imaging (MRSI) allows for noninvasive, localized analyses of brain biochemistry; however, minimal work has been devoted to the evaluation of 1H MRSI reproducibility. This study examined the reproducibility of 1H MRSI from five normal subjects on two occasions, separated by 10 days. Reproducibility of the MR signal was evaluated in the context of automated shimming, automated processing, and accurate subject repositioning. Reliability measures for physicochemical indices (choline moieties, creatine, N‐acetylaspartate, and myo‐inositol) were moderately concordant across repeat studies. Gain variation and repositioning results were excellent. It has been concluded that 1H MRSI reproducibility is adequate for serial studies of brain metabolism.
Expansion of the spectral bandwidth by spatial and chemical shift selective saturation in high‐speed magnetic resonance spectroscopic imaging
Authors: Hirata Satoshi , Bito Yoshitaka , Yamamoto Etsuji
Published: February 2011

A new spectral bandwidth expansion technique for highspeed magnetic resonance spectroscopic imaging (MRSI) based on an echo‐planar technique is presented. This expansion can be achieved by spatial and chemical shift selective saturation without increasing the total measurement time. In addition, displacement along the slice‐select direction due to chemical‐shift differences between the measured compounds is also suppressed. Experimental results are shown using a phantom consisting of benzene and acetone. High spatial resolution (1 × 1 mm2) and wide spectral bandwidth (1.5–1.8 kHz; the effective spectral bandwidth has been doubled) are obtained without the displacement along the slice‐select direction.
Characterization of the cerebral distribution of general anesthetics in vivo by two‐dimensional 19F chemical shift imaging
Authors: Venkatasubramanian Palamadai N. , Shen Ying J. , Wyrwicz Alice M.
Published: February 2011

The distribution of two fluorinated anesthetics, halothane and isoflurane, in rabbit brain was mapped during the course of their uptake using 19F NMR chemical shift imaging techniques. Use of a short phase‐encoding time and free induction decay acquisition minimized T2‐related signal losses in two‐dimensional chemical shift imaging. Localization of the brain and exclusion of surrounding tissues was achieved by the use of a surface coil. The spatial distribution of halothane and isoflurane in the brain was nonuniform and both anesthetics were detected predominantly in the cerebral cortex. During the early stages of uptake, anesthetic concentration in the brain was extremely low, but it continued to increase for several hours with sustained anesthetic delivery. Time‐dependent variations in anesthetic concentration were observed in different brain regions.
Assessment of the effect of haematocrit‐dependent arterial input functions on the accuracy of pharmacokinetic parameters in dynamic contrast‐enhanced MRI
Authors: Just Nathalie , Koh Dow‐Mu , D'Arcy James , Collins David J. , Leach Martin O.
Published: February 2011

The detection and prognosis of prostate cancer in its early stages are critically important. It is therefore essential to improve the existing dynamic contrast‐enhanced MRI (DCE MRI) techniques commonly used for the assessment of the tumour vascular environment. The goal of this study was to describe a method for the estimation of the arterial input function (AIF) in DCE MRI by measuring R2* values in the femoral artery of patients with early‐stage prostate cancer. The calculation of contrast agent concentrations was based on calibration curves determined in whole blood samples for a range of normal haematocrit (HCT) values (HCT = 0.35–0.525). Individual AIFs corrected for HCT were compared with individual AIFs calibrated with a mean whole blood [R2*–Gd‐DTPA‐BMA] [Gd‐DTPA‐BMA, gadolinium diethylenetriaminepentaacetate‐bis(methylamide) (gadodiamide)] curve at an assumed HCT = 0.44, as well as a population AIF at an assumed HCT = 0.45. The area under the curve of the first‐pass bolus ranged between 0.6 min mM at HCT = 0.53 and 1.3 min mM at HCT = 0.39. Significant differences in magnitude at peak contrast agent concentrations (HCT = 0.36, [Gd‐DTPA‐BMA]max = 9 ± 0.4 mM; HCT = 0.46, [Gd‐DTPA‐BMA]max = 4.0 ± 0.2 mM) were found. Using model‐based simulations, the accuracy of the kinetic parameters estimated using individual AIFs corrected for HCT demonstrated that, for the use of individual calibration curves with HCT values differing by more than 10%, Ktrans and kep values were largely underestimated (up to 60% difference for Ktrans). Moreover, blood volume estimates were severely underestimated. Estimates of kinetic parameters in early‐stage prostate cancer patients demonstrated that the efflux rate constant (kep) was influenced significantly by the definition of AIF. Regardless of whether an individually calibrated AIF or a population AIF (average of all individually calibrated AIFs) was used, pixel‐by‐pixel mapping of kep and vb in the prostate gland appeared to be more sensitive than with the usual biexponential approach. Copyright © 2011 John Wiley & Sons, Ltd.
Reproducibility of prefrontal γ‐aminobutyric acid measurements with J‐edited spectroscopy
Authors: Geramita Matthew , van der Veen Jan Willem , Barnett Alan S. , Savostyanova Antonina A. , Shen Jun , Weinberger Daniel R. , Marenco Stefano
Published: February 2011

γ‐Aminobutyric acid (GABA) is the chief inhibitory neurotransmitter of the human brain, and GABA‐ergic dysfunction has been implicated in a variety of neuropsychiatric disorders. Recent MRS techniques have allowed the quantification of GABA concentrations in vivo, and could therefore provide biologically relevant information. Few reports have formally characterized the reproducibility of these techniques, and differences in field strength, acquisition and processing parameters may result in large differences in measured GABA values. Here, we used a J‐edited, single‐voxel spectroscopy method of measurement of GABA + macromolecules (GABA + ) in the anterior cingulate cortex (ACC) and right frontal white matter (rFWM) at 3 T. We measured the coefficient of variation within subjects (CVw) and intra‐class correlation coefficients on two repeated scans obtained from 10 healthy volunteers with processing procedures developed in‐house for the quantification of GABA + and other major metabolites. In addition, by segmenting the spectroscopic voxel into cerebrospinal fluid, gray matter and white matter, and employing a linear regression technique to extrapolate metabolite values to pure gray and white matter, we determined metabolite differences between gray and white matter in ACC and rFWM. CVw values for GABA + /creatine, GABA + /H2O, GABA + , creatine, partially co‐edited glutamate + glutamine (Glx)/creatine, partially co‐edited Glx and N‐acetylaspartic acid (NAA)/creatine were all below 12% in both ACC and rFWM. After extrapolation to pure gray and pure white matter, CVw values for all metabolites were below 16%. We found metabolite ratios between gray and white matter for GABA + /creatine, GABA + , creatine, partially co‐edited Glx and NAA/creatine to be 0.88 ± 0.21 (standard deviation), 1.52 ± 0.32, 1.77 ± 0.4, 2.69 ± 0.74 and 0.70 ± 0.05, respectively. This study validates a reproducible method for the quantification of brain metabolites, and provides information on gray/white matter differences that may be important in the interpretation of results in clinical populations. Published in 2011 by John Wiley & Sons, Ltd.
Uncertainty feature optimization: An implicit paradigm for problems with noisy data
Authors: Eggenberg Niklaus , Salani Matteo , Bierlaire Michel
Published: February 2011

Optimization problems with noisy data solved using stochastic programming or robust optimization approaches require the explicit characterization of an uncertainty set U that models the nature of the noise. Such approaches depend on the modeling of the uncertainty set and suffer from an erroneous estimation of the noise.

In this article, we introduce a framework that considers the uncertain data implicitly. We define the concept of Uncertainty Features (UF), which are problem‐specific structural properties of a solution. We show how to formulate an uncertain problem using the Uncertainty Feature Optimization (UFO) framework as a multi‐objective problem. We show that stochastic programming and robust optimization are particular cases of the UFO framework. We present computational results for the Multi‐Dimensional Knapsack Problem (MDKP) and discuss the application of the framework to the airline scheduling problem. © 2011 Wiley Periodicals, Inc. NETWORKS, 2011
Erythropoietin protects against apoptosis and increases expression of non‐neuronal cell markers in the hypoxia‐injured developing brain
Authors: Yamada Miko , Burke Christopher , Colditz Paul , Johnson David W , Gobe Glenda C
Published: February 2011

Erythropoietin (EPO) is a cytokine hormone with cytoprotective effects in many tissues including the brain. Although the benefits of administration of recombinant human EPO (rhEPO) for neonatal hypoxic brain injury have been demonstrated in neuronal tissue, the effect on non‐neuronal cell populations is unclear. We tested the hypothesis that rhEPO would not only protect neuronal cells but also glial cells at a stage of brain development where their maturation was particularly sensitive, and also protect the vasculature. This was evaluated in a rat model of hypoxic injury. 1000 IU/kg rhEPO was delivered intraperitoneally at the start of 4 h hypoxia or normoxia. Treatment groups of neonatal rats (day of birth, at least N = 10 per group) were as follows: normoxia; normoxia plus rhEPO; hypoxia (8% FiO2 delivered in temperature‐controlled chambers); and hypoxia plus rhEPO. Day of birth in rats is equivalent to human gestation of 28–32 weeks. The effects of rhEPO administration, especially to non‐neuronal cell populations, and the associated molecular pathways, were investigated. Apoptosis was increased with hypoxia and this was significantly reduced with rhEPO (p < 0.05). The neuronal marker, microtubule‐associated protein‐2, increased in expression (p < 0.05) when apoptosis was significantly reduced by rhEPO. In addition, compared with hypoxia alone, rhEPO‐treated hypoxia had the following significant protein expression increases (p < 0.05): the intermediate filament structural protein nestin; myelin basic protein (oligodendrocytes); and glial fibrillary acidic protein (astrocytes). In conclusion, rhEPO protects the developing brain via anti‐apoptotic mechanisms and promotes the health of non‐neuronal as well as neuronal cell populations at a time when loss of these cells would have long‐lasting effects on brain function. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Ewing sarcoma cells express RANKL and support osteoclastogenesis
Authors: Taylor Richard , Knowles Helen J , Athanasou Nicholas A
Published: February 2011

Ewing sarcoma (ES) is a primary malignant round cell tumour of bone characterized by rapid and extensive osteolysis. Cellular mechanisms underlying the rapid bone resorption in ES have not been characterized. Osteoclasts are marrow‐derived multinucleated cells that effect tumour osteolysis. The role of ES tumour cells in influencing osteoclast formation and/or directly contributing to the osteolysis in ES has not been determined. Using a tissue culture bioassay, we found that lacunar resorption is not carried out by (CD99+) ES tumour cells, but by (CD68+) macrophage/osteoclast‐like cells; this resorption occurred in the absence of the osteoclastogenic factor, receptor activator of nuclear factor κB ligand (RANKL). ES cell lines cultured directly on dentine slices did not resorb the mineral or organic components of the bone matrix. Immunohistochemistry of ES tissue microarrays, western blotting, and RT‐PCR studies showed that ES cells strongly expressed both RANKL and macrophage‐colony stimulating factor (M‐CSF), two major osteoclastogenic factors. When co‐cultured with human monocytes, ES cells induced the formation of TRAP+ osteoclastic cells. Conditioned medium from cultured ES cells did not result in osteoclast formation, indicating that cell–cell contact is required for ES‐induced osteoclastogenesis. Our findings indicate that ES cells do not resorb bone directly but that they may support osteoclast formation by a RANKL‐dependent mechanism. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Transforming growth factor‐beta type 1 receptor (ALK5) and Smad proteins mediate TIMP‐1 and collagen synthesis in experimental intestinal fibrosis
Authors: Medina Carlos , Santos‐Martinez Maria Jose , Santana Alfredo , Paz‐Cabrera Maria Cristina , Johnston Michael J , Mourelle Marisabel , Salas Antonio , Guarner Francisco
Published: February 2011

Transforming growth factor β (TGF‐β) is known to play a key role in intestinal fibrosis; however, the underlying mechanisms are not well understood. TGF‐β signal transduction is through TGF‐β receptors, including the TGF‐β type 1 receptor. Most cell types contain a TGF‐β type 1 receptor form known as activin receptor‐like kinase 5 (ALK5), which propagates the signal to the nucleus through the phosphorylation of Smad2 and Smad3 proteins. Therefore, we assessed the effect of the disruption of TGF‐β/ALK5/Smad signalling by an ALK5 inhibitor (SD‐208) in two experimental animal models of intestinal fibrosis: anaerobic bacteria‐ and trinitrobenzensulphonic acid‐induced colitis. In addition, isolated myofibroblasts were pretreated with SD‐208 and exposed to recombinant TGF‐β1. Finally, myofibroblasts were transfected with ALK5, Smad2, and Smad3‐specific siRNA. Up‐regulation of ALK5 and TIMP‐1, phosphorylation of Smad2 and Smad3 proteins, and increased intestinal wall collagen deposition were found in both experimental animal models. These effects were decreased by SD‐208. TGF‐β1 treatment also induced phosphorylation of Smad2 and Smad3 and up‐regulation of ALK5 protein, TIMP‐1, and α2 type 1 collagen gene expression in isolated myofibroblasts. Again these effects were inhibited by SD‐208. Also, ALK5, Smad2, and Smad3 siRNA abolished the induction of TIMP‐1 and α2 type 1 collagen. Our findings provide evidence that the TGF‐β/ALK5/Smad pathway participates in the pathogenesis of experimental intestinal fibrosis. These data show promise for the development of an effective therapeutic intervention in this condition. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
FMNL2 is a positive regulator of cell motility and metastasis in colorectal carcinoma
Authors: Zhu Xi‐ling , Zeng Yuan‐feng , Guan Jian , Li Yu‐fa , Deng Yong‐jian , Bian Xiu‐wu , Ding Yan‐qing , Liang Li
Published: February 2011

FMNL2 is a member of diaphanous‐related formins which act as effectors of Rho family GTPases and control the actin‐dependent processes such as cell motility or invasion. We previously found that FMNL2 overexpression in metastatic cell lines and tissues of colorectal carcinoma is associated with more aggressive tumour behaviour. Here we used gain‐of‐function and loss‐of‐function approaches to investigate the effects of FMNL2 on colorectal carcinoma in vitro and in vivo. Forced expression of FMNL2 caused a significant increase in tumour cell proliferation, motility, invasion in vitro, and metastasis in vivo, whereas FMNL2 depletion showed opposite effects. We examined gene expression profiles following knockdown of FMNL2 in SW480/M5 cells. Expression of 323 genes was up‐regulated by more than two‐fold, whereas 222 genes were down‐regulated by more than two‐fold in FMNL2‐depleting SW480/M5 cells. Gene ontology analysis showed that most of genes belong to functional categories such as cell cycle, cytoskeleton, transcription factor, and G‐protein modulator. Pathway analysis revealed that cytoskeletal regulation by the Rho GTPase pathway, the Wnt pathway, the G‐protein pathway, and the P53 pathway were affected by FMNL2. Many of these genes are in functional networks associated with cell proliferation, metastasis, Wnt or the Rho signalling pathway involved in the regulation of FMNL2. The expression of five differentially expressed genes including CXXC4, CD200, VAV1, CSF1, and EPHA2 was validated by real‐time PCR and western blot analysis. Thus, FMNL2 is a positive regulator of cell motility, invasion, and metastasis of colorectal carcinoma. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Predictors of independent living status in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study
Authors: Kunin‐Batson Alicia , Kadan‐Lottick Nina , Zhu Liang , Cox Cheryl , Bordes‐Edgar Veronica , Srivastava Deo Kumar , Zeltzer Lonnie , Robison Leslie L. , Krull Kevin R.
Published: February 2011

Background

Adult survivors of childhood cancer and their siblings are compared on one of the most salient developmental milestones of adulthood, the ability to live independently.

Procedure

Adult survivors of childhood cancers (n = 6,047) and siblings (n = 2,326), all 25 years of age and older, completed a long‐term follow‐up questionnaire that assessed adaptive, neurocognitive, and psychological functioning, as well as demographic and health status. Multivariable logistic regression analyses and structural equation modeling (SEM) were used to identify predictors of independent living.

Results

Compared to siblings (n = 206, 8.7%), survivors (n = 1063; 17.7%) were more than twice as likely to live dependently (OR 2.07; 95% confidence interval [CI] 1.77–2.42). Survivors diagnosed with CNS tumors (OR 0.13, 95% CI 0.10–0.18) or leukemia (OR 0.29, 95% CI 0.23–0.27) were significantly less likely to live independently compared to those diagnosed with Hodgkin lymphoma. Other risk factors for reduced independent living included cranial radiation (≤24 Gy OR 0.76, 95% CI 0.62–0.93; >24 Gy OR 0.31, 95% CI 0.24–0.41), use of neuroleptic, anticonvulsant, or psychostimulant medication (OR 0.32, 95% CI 0.24–0.43), attention and processing speed problems (OR 0.58, 95% CI 0.47–0.71), poor physical functioning (OR 0.49, 95% CI 0.38–0.63), depression (OR 0.68, 95% CI 0.53–0.88), and racial/ethnic minority status (OR 0.39, 95% CI 0.30–0.51). SEM demonstrated that neurocognitive functioning had both direct effects on independent living status, and indirect effects through use of neurologically directed medication, depression, and poor mental health.

Conclusion

Adult survivors of childhood cancer who experience neurocognitive, psychological, or physical late effects are less likely to live independently as adults. Pediatr Blood Cancer 2011; 57: 1197–1203. © 2011 Wiley Periodicals, Inc.
Platelet disorders in children: A diagnostic approach
Authors: Israels Sara J. , Kahr Walter H.A. , Blanchette Victor S. , Luban Naomi L.C. , Rivard Georges E. , Rand Margaret L.
Published: February 2011

The investigation of children with suspected inherited platelet disorders is challenging. The causes of mucocutaneous bleeding are many, and specialized testing for platelet disorders can be difficult to access or interpret. An algorithm developed for the investigation of suspected platelet disorders provides a sequential approach to evaluating both platelet function abnormalities and thrombocytopenia. Investigation begins with a clinical evaluation and laboratory testing that is generally available, including platelet counting, peripheral blood cell morphology, and aggregometry. Based on results of initial investigations, the algorithm recommends specialized testing for specific diagnoses, including flow cytometry, immunofluorescence microscopy, electron microscopy, and mutational analysis. Pediatr Blood Cancer 2011;56:975–983. © 2011 Wiley‐Liss, Inc.
Fludarabine, cyclophosphamide, doxorubicin (FCD), and rituximab: A remission induction therapy for aggressive pediatric post‐transplant lymphoproliferative disease (PTLD)
Authors: Giraldi Eugenia , Provenzi Massimo , Fiocchi Roberto , Colledan Michele , Cornelli Pieremilio , Torre Giuliano , Rambaldi Alessandro , Conter Valentino
Published: February 2011

Management of aggressive, usually late‐occurring, post‐transplant lymphoproliferative disorders (PTLDs), a life‐threatening complication after solid organ transplants, remains controversial. Four children affected by aggressive CD20+ PTLDs received a chemo‐immunotherapy regimen for remission induction based on fludarabine, cyclophosphamide, doxorubicin, and rituximab, associated with a rapid discontinuation of immunosuppression (IS). Subsequent consolidation chemotherapy consisted of Berlin‐Frankfurt‐Münster‐modified blocks. All patients achieved a complete remission, which persisted for 25, 68+, 80+, and 103+ months after diagnosis. Therapy was well tolerated. No patients developed allograft rejection during PTLD treatment. Our experience suggests that this chemo‐immunotherapeutic approach may be an effective treatment strategy while allowing for a concomitant discontinuation of IS. Pediatr Blood Cancer 2011; 57: 324–328. © 2011 Wiley‐Liss, Inc.
Preparation of monodispersed silica spheres and electrospinning of poly(vinyl alcohol)/silica composite nanofibers
Authors: Wang S.H. , Sun L.G. , Zhang B. , Wang C. , Li Z.W. , He J.Z. , Zhang J. , Xie Y.
Published: February 2011

In this study, monodispersed silica spheres were successfully synthesized by seed‐growth method and they can be highly dispersed in the poly(vinyl alcohol)(PVA) solution. PVA/silica composite fibers were fabricated by electrospinning the composite solutions containing different amount of silica. Further investigation showed that the size distribution of silica sphere was monodispersed and the spheres were homogeneously dispersed in the fibers individually. The composite fibers showed an uniform and continuous morphology with a average diameter of 298–345 nm. The as‐spun nanofibers were characterized by Field Emission Scanning Electron Microscope (FE‐SEM), transmission electron microscopy (TEM), X‐ray diffraction (XRD), and thermal gravimetric analysis (TGA). POLYM. COMPOS., 2011. © 2011 Society of Plastics Engineers
Poly(lactic acid)/titanium dioxide nanocomposite films: Influence of processing procedure on dispersion of titanium dioxide and photocatalytic activity
Authors: Zhu Yunfeng , Buonocore Giovanna G. , Lavorgna Marino , Ambrosio Luigi
Published: February 2011

Poly(lactic acid)/titanium dioxide (TiO2) composite films were prepared by direct melt processing using three different procedures (i.e., compression molding, twin‐screw melt extrusion, and melt extrusion and thermoforming). The effect of TiO2 loading and processing procedures on the phase morphology and on the thermal, mechanical, and barrier properties of the obtained nanocomposites were analyzed respectively by field‐emission scanning electron microscopy‐energy dispersive spectrometry, differential scanning calorimetry, universal testing machine, and water vapor and oxygen permeability measurements. The incorporation of TiO2 nanoparticles into the poly(lactic acid) matrix increased the crystallinity and improved the barrier properties of the composites. The maximum tensile strength was achieved at the 2% content of TiO2 for the films produced by compression molding and twin‐screw melt extrusion, whereas the tensile strength for films produced by melt extrusion and thermoforming decreases markedly with an increasing TiO2 content. The photocatalytic activities of the obtained nanocomposites were investigated by analyzing the degradation of methyl orange. Results confirmed that the processing procedures and the distribution of TiO2 in the polymer matrix are the key parameters, which rule the photocatalytic behavior of composite films. POLYM. COMPOS., 2011. © 2011 Society of Plastics Engineers
Normal ranges of fetal nasal bone length during the second trimester in an Iranian population
Authors: Rahimi‐Sharbaf Fatemeh , Tahmasebpour Ahmad‐Reza , Pirjani Reihaneh , Ghaffari Saeed Reza , Rahimi‐Foroushani Abbas
Published: February 2011

Objective

To provide a normal reference range for nasal bone length (NBL) during the second trimester of pregnancy in an Iranian population.

Methods

This cross‐sectional study was performed on 3201 fetuses at 15 to 28 weeks of gestational age (GA). Both singleton and twin fetuses were evaluated. The relationship between NBL and GA was determined and percentile values for each gestational week were provided.

Results

NBL measurement was obtained in 98% of singleton and 96% of twin fetuses. There was a linear relationship between GA and NBL both in singleton (R2 = 0.62) and in twin (R2 = 0.74) fetuses. There was no significant difference between twins regarding NBL (p = 0.18).

Conclusion

We have provided the normal reference range for NBL during the second trimester in an Iranian population. NBL in singleton and twin fetuses is similar and there is no significant difference between twins regarding NBL. Copyright © 2011 John Wiley & Sons, Ltd.
Synthesis, characterization, and property of amphiphilic fluorinated abc‐type triblock copolymers
Authors: Guo Wenjuan , Tang XinDe , Xu Jing , Wang Xin , Chen Ye , Yu Faqi , Pei MeiShan
Published: February 2011

Novel amphiphilic fluorinated ABC‐type triblock copolymers composed of hydrophilic poly(ethylene oxide) monomethyl ether (MeOPEO), hydrophobic polystyrene (PSt), and hydrophobic/lipophobic poly(perfluorohexylethyl acrylate) (PFHEA) were synthesized by atom transfer radical polymerization (ATRP) using N,N,N′,N″,N″‐pentamethyldiethylenetriamine (PMDETA)/CuBr as a catalyst system. The bromide‐terminated diblock copolymers poly(ethylene oxide)‐block‐polystyrene (MeOPEO‐b‐PSt‐Br) were prepared by the ATRP of styrene initiated with the macroinitiator MeOPEO‐Br, which was obtained by the esterification of poly(ethylene oxide) monomethyl ether (MeOPEO) with 2‐bromoisobutyryl bromide. A fluorinated block of poly(perfluorohexylethyl acrylate) (PFHEA) was then introduced into the diblock copolymer by a second ATRP process to synthesize a novel ABC‐type triblock copolymer, poly(ethylene oxide)‐block‐polystyrene‐block‐poly(perfluorohexylethyl acrylate) (MeOPEO‐b‐PSt‐b‐PFHEA). These block copolymers were characterized by means of proton nuclear magnetic resonance (1H NMR) and gel permeation chromatography (GPC). Water contact angle measurements revealed that the polymeric coating of the triblock copolymer (MeOPEO‐b‐PSt‐b‐PFHEA) shows more hydrophobic than that of the corresponding diblock copolymer (MeOPEO‐b‐PSt). Bovine serum albumin (BSA) was used as a model protein to evaluate the protein adsorption property and the triblock copolymer coating posseses excellent protein‐resistant character prior to the corresponding diblock copolymer and polydimethylsiloxane. These amphiphilic fluoropolymers can expect to have potential applications for antifouling coatings and antifouling membranes. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Copolymerization of 2‐hydroxyethyl methacrylate with a comonomer with spiroacetal moiety
Authors: Chiriac Aurica P. , Nita Loredana E. , Nistor Manuela T.
Published: February 2011

The study reports the synthesis of a copolymer based on 2‐hydroxyethyl methacrylate and 3,9‐divinyl‐2,4,8,10‐tetraoxaspiro[5.5]undecane (U) acquired through radical polymerization in the presence of 2,2′‐azobis(2‐methylpropionitrile). The attempt was to have a solid content as high as 10 wt %. The polymerization process was conducted in the presence of a classic ionic surfactant—sodium lauryl sulfate—and comparatively using two variants of protective colloid β‐cyclodextrin and poly(aspartic acid), respectively. The prepared dispersions were characterized from the viewpoint of their hydrodynamic radius, zeta potential, and conductivity evolution during syntheses. The mean particle size and size distribution and zeta potential and conductivity were also evaluated for the synthesized polymeric particles. The compositions of the polymers were confirmed by FTIR and 1H NMR spectra, and also, the thermal stability of the polymeric compounds was evaluated. SEM and AFM investigations of the polymer morphology are also presented. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Enhanced performance of photorefractive poly(N‐vinyl carbazole) composites
Authors: Tsutsumi Naoto , Dohi Akihito , Nonomura Asato , Sakai Wataru
Published: February 2011

We present the enhanced photorefractive performance of high molecular weight poly(N‐vinyl carbazole) (PVCz)‐based composites. Higher diffraction efficiency with faster speed of grating build‐up was obtained by optimizing the composition of the PVCz composites. At relatively low applied electric field of E = 45 V μm−1, diffraction efficiency of 26% for p‐polarized probe beam and corresponding that of 5.1% for s‐polarized probe beam were measured with faster grating build‐up speed of 48.3 s−1 for the composite with 2,4,7‐trinitrofluorenone (TNF) as a sensitizer. Fastest speed of grating build‐up of 100 s−1 and large optical gain up to 110 cm−1 were measured at E = 80 V μm−1 for the composite with fullerene derivative of PCBM as a sensitizer. These improved performances are due to a large orientational enhancement effect with faster response speed in addition to Pockels effect for the samples with appropriate glass transition temperature. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011
Enhanced Cellular Functions on Polycaprolactone Tissue Scaffolds by O2 Plasma Surface Modification
Authors: Yildirim Eda D. , Pappas Daphne , Güçeri Selçuk , Sun Wei
Published: February 2011

This paper reports a study of using an oxygen‐based plasma modification to alter physicochemical properties of three‐dimensional (3D) PCL scaffolds and to improve mouse osteoblast cells attachment, proliferation, and osteoblastic differentiation. Different plasma modification times (1, 3, and 5‐min) and their effects on surface physicochemical properties were measured by contact angle measurement, surface energy calculation (Owens–Wendth Method), surface chemistry (XPS), and the surface topography (AFM). The effect of oxygen‐based plasma modification on attachment, proliferation, and osteoblastic differentiation were examined by shear flow assay, alamarBlue assay, scanning electron microscopy (SEM), and osteoblastic differentiation markers. Results of the contact angle measurement, total solid surface energy, surface chemistry, and roughness revealed that oxygen‐based plasma modification increased surface hydrophilicity, total surface energy, total amount of oxygen containing groups, and the surface roughness. A positive effect of plasma modification on cell proliferation on 3D PCL scaffolds was observed at the osteoblastic differentiation stage which was evaluated by the alkaline phosphatase (ALP) activity, osteocalcin protein secretion, and calcium mineralization. The higher ALP activity and osteocalcin secretion were detected from the cells on 3‐min plasma modified PCL surface compared to unmodified samples. The calcium mineralization and SEM micrographs data also showed that there was a higher mineralized matrix deposition on 3‐min plasma modified PCL scaffolds compared to unmodified scaffolds. These results suggest that the 3‐min plasma modification can accelerate differentiation phase of osteoblast through improving cell–scaffold interaction.

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Possible ligand release pathway of dipeptidyl peptidase IV investigated by molecular dynamics simulations
Authors: Li Cui , Shen Jie , Li Weihua , Lu Chunhua , Liu Guixia , Tang Yun
Published: February 2011

Dipeptidyl peptidase IV (DPP4) is an important target for the treatment of Type II diabetes mellitus. The crystal structure of DPP4 demonstrates that there are two possible pathways to the active site, a side opening and a β propeller opening. However, it still lacks quantitative evidence to illustrate which pathway is more favorable for inhibitor to enter into or release from the active site. In this study, conventional and steered molecular dynamics simulations were performed to explore the details of inhibitor Q448 release from the active site of DPP4 via the two potential pathways. The comparisons of force and work together with potentials of mean force results suggested that the side opening might be more favorable for the inhibitor to pass through. Moreover, Glu205‐Glu206 and Phe357 were recognized as two “key residues” in the active site for inhibitor binding. Accordingly, suggestions for further inhibitor design wereprovided. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Is it really an independent protection layer?
Authors: Dowell A.M.
Published: February 2011

Layer of protection analysis (LOPA) is a simplified chemical process risk assessment tool that is used to determine if sufficient independent protection layers (IPLs) are in place to meet an organization's risk tolerance criteria for a particular hazardous scenario. LOPA can determine how much additional risk reduction is needed for the scenario and can help in specifying the additional protection layers.

The Center for Chemical Process Safety books, Layer of Protection Analysis—Simplified Process Risk Assessment (Center for Chemical Process Safety, Layer of Protection Analysis: Simplified Process Risk Assessment, American Institute of Chemical Engineers, New York, NY, 2001) and Guidelines for Safe and Reliable Instrumented Protective Systems (Center for Chemical Process Safety, Guidelines for Safe and Reliable Instrumented Protective Systems, American Institute of Chemical Engineers, New York, NY, 2007), identify required attributes of independent protective layers. In more than 15 years experience working with LOPA, I have frequently observed confusion about these attributes among LOPA analysts, protection layer implementers, and operations personnel (Study and Champion, Process Saf Prog 28 (2009), 300–307).

Therefore, this article discusses the characteristics of IPLs, gives examples to avoid confusion and misapplication of the characteristics, gives an easily remembered phrase to screen candidate IPLs, and provides sample tools to confirm IPL compliance with the characteristics. The article discusses the importance of a safety requirements specification for safety‐instrumented functions and proposes analogous documentation for other IPLs. The article gives guidance to determine when protection layers or scenarios require more detailed analysis such as event tree analysis or fault tree analysis. analysis. © 2011 American Institute of Chemical Engineers Process Saf Prog, 2011
Improving operational discipline to prevent loss of containment incidents
Authors: Vaughen Bruce K. , Klein James A.
Published: February 2011

Process safety and risk management systems are implemented to reduce injuries and process incidents. The effectiveness of these systems is dependent on the company's implementation and support for operational discipline (OD)‐related programs to ensure that the process safety management system requirements are followed day‐to‐day at all levels of the organization. However, OD‐program‐related problems continue to contribute to process incidents, including loss of containment (LOC) incidents, especially since they may not be formally addressed during incident investigations. This article provides a brief historical overview of major LOC incidents, describes how poor OD increases process safety risk and can contribute to LOC incidents, and provides an incident investigation tool to help monitor and improve OD characteristics. © 2011 American Institute of Chemical Engineers Process Saf Prog, 2011
Analogues of trypsin inhibitor SFTI‐1 modified in the conserved P1′ position by synthetic or non‐proteinogenic amino acids retain their inhibitory activity
Authors: Rafał Łukajtis , Anna Łȩgowska , Magdalena Wysocka , Dawid Dȩbowski , Adam Lesner , Krzysztof Rolka
Published: February 2011

A series of linear and monocyclic (with a disulfide bridge only) analogues of trypsin inhibitor SFTI‐1 modified in the P1 and/or P1′ positions were synthesized by the solid‐phase method. In the substrate specificity P1 position, Phe or N‐benzylglycine (Nphe) were introduced, whereas the conserved Ser6 in Bownam‐Birk (BBI) inhibitors was replaced by Hse (L‐homoserine), Nhse [N‐(2‐hydroxyethyl)glycine], Sar, and Ala. Kinetic studies of interaction of the analogues with bovine α‐chymotrypsin have shown that in monocyclic (but not linear) analogues, Hse and Nhse are tolerated to afford potent inhibitors. This is the first evidence that the absolutely conserved Ser present in the inhibitor's P1′ position can be successfully replaced by a synthetic derivative. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.