bluuebunny/crossref_metadata_2025 huggingface dataset:
Accounting for haplotype phase uncertainty in linkage disequilibrium estimation
Authors: Kulle B. , Frigessi A. , Edvardsen H. , Kristensen V. , Wojnowski L.
Published: October 2007

The characterization of linkage disequilibrium (LD) is applied in a variety of studies including the identification of molecular determinants of the local recombination rate, the migration and population history of populations, and the role of positive selection in adaptation. LD suffers from the phase uncertainty of the haplotypes used in its calculation, which reflects limitations of the algorithms used for haplotype estimation. We introduce a LD calculation method, which deals with phase uncertainty by weighting all possible haplotype pairs according to their estimated probabilities as evaluated by PHASE. In contrast to the expectation‐maximization (EM) algorithm as implemented in the HAPLOVIEW and GENETICS packages, our method considers haplotypes based on the entire genetic information available for the candidate region. We tested the method using simulated and real genotyping data. The results show that, for all practical purposes, the new method is advantageous in comparison with algorithms that calculate LD using only the most probable haplotype or bilocus haplotypes based on the EM algorithm. The new method deals especially well with low LD regions, which contribute strongly to phase uncertainty. Altogether, the method is an attractive alternative to standard LD calculation procedures, including those based on the EM algorithm. We implemented the method in the software suite R, together with an interface to the popular haplotype calculation package PHASE. Genet. Epidemiol. 2008. ©2007 Wiley‐Liss, Inc.
Effect of an interdisciplinary educational program on antipsychotic prescribing among nursing home residents with dementia
Authors: Monette Johanne , Champoux Nathalie , Monette Michèle , Fournier Lynn , Wolfson Christina , du Fort Guillaume Galbaud , Sourial Nadia , Le Cruguel Jean‐Pierre , Gore Brian
Published: October 2007

Objective

To assess the effect of an interdisciplinary educational program in reducing the use of antipsychotics in nursing home residents with dementia.

Methods

We conducted a longitudinal pilot study to test the implementation of a 7‐month interdisciplinary educational program in a fixed cohort of residents with dementia receiving antipsychotics. The program included consciousness‐raising, educational sessions, and clinical follow‐up. Administrators, physicians, pharmacists, nursing staff, and personal care attendants were involved. The effect of the program was assessed over a 6‐month period, in terms of the proportion of discontinuations and dose reductions of antipsychotics. Repeated measures for use of other psychotropics and restraints, frequency of disruptive behaviors, and stressful events experienced by nursing staff and personal care attendants were simultaneously assessed.

Results

Among the 81 residents still present at the end of the program, there were 40 (49.4%) discontinuations and 11 (13.6%) dose reductions. No significant changes were found in the use of other psychotropics, the use of restraints, or in the number of stressful events experienced by nursing staff and personal care attendants. The frequency of disruptive behaviors decreased significantly over the 6‐month period (p < 0.001).

Conclusions

Our interdisciplinary educational program led to a substantial reduction in the number of residents receiving antipsychotics and to a decrease in the frequency of disruptive behaviors. Our findings suggest that implementation of recognized practice guidelines could be an effective way to target residents who might not benefit from antipsychotics or who may tolerate a dose reduction. Copyright © 2007 John Wiley & Sons, Ltd.
Rain‐gauge network evaluation and augmentation using geostatistics
Authors: Cheng Ke‐Sheng , Lin Yun‐Ching , Liou Jun‐Jih
Published: October 2007

Rain‐gauge networks are often used to provide estimates of area average rainfall or point rainfalls at ungauged locations. The level of accuracy a network can achieve depends on the total number and locations of gauges in the network. A geostatistical approach for evaluation and augmentation of an existing rain‐gauge network is proposed in this study. Through variogram analysis, hourly rainfalls are shown to have higher spatial variability than annual rainfalls, with hourly Mei‐Yu rainfalls having the highest spatial variability. A criterion using ordinary kriging variance is proposed to assess the accuracy of rainfall estimation using the acceptance probability defined as the probability that estimation error falls within a desired range. Based on the criterion, the percentage of the total area with acceptable accuracy Ap under certain network configuration can be calculated. A sequential algorithm is also proposed to prioritize rain‐gauges of the existing network, identify the base network, and relocate non‐base gauges. Percentage of the total area with acceptable accuracy is mostly contributed by the base network. In contrast, non‐base gauges provide little contribution to Ap and are subject to removal or relocation. Using a case study in northern Taiwan, the proposed approach demonstrates that the identified base network which comprises of approximately two‐thirds of the total rain‐gauges can achieve almost the same level of performance (expressed in terms of percentage of the total area with acceptable accuracy) as the complete network for hourly Mei‐Yu rainfall estimation. The percentage of area with acceptable accuracy can be raised from 56% to 88% using an augmented network. A threshold value for the percentage of area with acceptable accuracy is also recommended to help determine the number of non‐base gauges which need to be relocated. Copyright © 2007 John Wiley & Sons, Ltd.
Water table and transpiration dynamics in a seasonally inundated Melaleuca quinquenervia forest, north Queensland, Australia
Authors: McJannet David
Published: October 2007

Water table fluctuations and transpiration were monitored in a seasonally inundated Melaleuca quinquenervia floodplain forest at Cowley Beach, north Queensland, Australia. Techniques were developed to reconstruct inundation duration and seasonal and inter‐annual variability at this site using long‐term stream flow data. It was estimated that the median duration of inundation in any year was 75 days with maximum and minimum durations of 167 days and 8 days, respectively. Measurements of individual tree transpiration using heat‐pulse techniques showed a strong relationship between tree size and tree water use, which was used for scaling to stand transpiration. Stand transpiration rates were found to be closely tied to atmospheric drivers of evaporation, and transpiration of M. quinquenervia was found to be unaffected by inundation. This ability to transpire during inundation may be due to physiological adaptations of this species. These adaptations are believed to include dynamic root systems that can quickly respond to rising and falling water tables and dense networks of fine apogeotropic roots, which grow on and within the papery bark. Rates of stand transpiration remained low throughout the study (0·46 mm d−1, 164 mm y−1) despite the fact that transpiration was not limited by solar energy inputs or soil moisture deficit. Low stand transpiration was attributed to the low density, stunted nature and small sapwood area of trees at this site. Copyright © 2007 John Wiley & Sons, Ltd.
From subordination to parity: an international comparison of equity securities law claims in insolvency proceedings
Authors: Sarra Janis
Published: October 2007

Securities law claims in insolvency proceedings raise important questions of allocation of risk and remedies. In the ordinary course of business, equity claims come last in the hierarchy of claims during insolvency. What is less clear is whether this should encompass claims arising from the violation of public statutes designed to protect equity investors. Discerning the optimal allocation of risk is a complex challenge if one is trying to maximize the simultaneous advancement of securities law and insolvency law public policy goals. From a securities law perspective, there must be confidence in meaningful remedies for capital markets violations if investors are to continue to invest. From an insolvency perspective, creditors make their pricing and credit availability choices based on certainty regarding their claims and shifting those priorities may affect the availability of credit. The critical question is the nature of the claim advanced by the securities holder and whether subordination of securities law claims gives rise to inappropriate incentives for corporate officers within the insolvency law regime. A comparative analysis reveals that the U.S. has provided a limited statutory exception to complete subordination through the fair funds provision of the Sarbanes‐Oxley Act by allowing SEC claims for penalties and disgorgement to rank equally with unsecured claims even though the funds are distributed to shareholders. The U.K. and Australian schemes permit shareholders to claim directly as unsecured creditors for fraudulent acts and misrepresentation by the issuer. In contrast, Canadian law is underdeveloped in its treatment of such claims. The paper canvasses the policy options available to reconcile securities law and insolvency law claims, including a discussion of the appropriate gatekeeping role for regulatory authorities and the courts, and the need for a framework that offers fair and expeditious resolution of such claims. If the public policy goal of both securities law and insolvency law is to foster efficient and cost‐effective capital markets, it seems that the systems need to be better reconciled than currently. The paper also examines the codified response to the time and resources consumed in various common law tracing claims by customers in a securities firm insolvency. Copyright © 2007 John Wiley & Sons, Ltd.
Effects of hydroxyapatite additive content on the bioactivity and biomechanical compatibility of bioactive nano‐titania ceramics
Authors: Li Zhensheng , Qu Yang , Yang Bangcheng , Zhang Bo , Kim Hyun‐Min , Zhao Haibo , Zhang Xingdong
Published: October 2007

Bioactive nano‐titania ceramics with excellent biomechanical compatibility and bioactivity were prepared by using hydroxyapatite (HA) additive as grain growth inhibitor with different contents. After sintered at 1000 °C with pressureless sintering method, the grain size of nano‐titania ceramic was less than 70 nm. Mechanical test results showed that compressive strengths of the nano ceramics were from 137.5 to 275.6 MPa, elastic moduli from 7 to 8 GPa, and bending strengths from 38.67 to 111.96 MPa by increasing HA additive content from 1 to 20%. The mechanical properties of nano‐titania ceramics were analogous to that of the human bone. The content of HA additive played an important role in adjusting the grain/particle size of nano‐titania ceramics, which had a great effect on the osteoblasts proliferation in the cell culture experiments. The cell culture experiments also demonstrated that the bioactive HA additive itself also had a great effect on the cytocompatibility of the nano‐titania ceramics. The results of the present study indicated that the content of HA additive not only had effect on the bioactivity of the nano‐titania ceramics because of the bioactivity of the additive itself, but also had effect both on the biomechanical compatibility and bioactivity of the nano‐titania ceramics by adjusting the grain/particle size of the ceramics. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Preparation and immobilization of soluble eggshell membrane protein on the electrospun nanofibers to enhance cell adhesion and growth
Authors: Jia Jun , Duan Yuan‐Yuan , Yu Jian , Lu Jian‐Wei
Published: October 2007

Nonwoven poly(ε‐caprolactone) (PCL) nanofibers were prepared by electrospinning technology, and a novel natural bioactive material, soluble eggshell membrane protein (SEP), which is made from natural eggshell membrane (ESM), was then immobilized on the nanofibers after the surface modification. The SEP‐immobilized fibrous mat was observed and characterized using scanning electron microscopy (SEM), contact angle measurement, Fourier transform infrared attenuated total reflection spectroscopy (ATR‐FTIR), X‐ray photoelectron spectroscopy (XPS), and tensile mechanical tests. Then the primary human dermal fibroblasts (HDFs) were cultured to evaluate the in vitro biocompatibility of SEP‐grafted electrospun PCL nanofibers. The results confirmed the successful immobilization of SEP on the nanofibers and also indicated that the hydrophilicity of the PCL nanofibers has been greatly improved by the SEP grafting. The results of MTT testing, SEM, and laser scanning confocal microscope (LSCM) showed that SEP immobilization can obviously enhance the attachment, spreading, and proliferation of human dermal fibroblasts (HDFs) compared with the pristine material. The SEP‐grafted PCL nanofibers can be expected to biomimic and regenerate the natural structure of eggshell membrane and to be a potential material for tissue engineering scaffold and guided tissue regeneration barrier membrane. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Incorporation of titanium into calcium silicate improved their chemical stability and biological properties
Authors: Wu Chengtie , Ramaswamy Yogambha , Soeparto Andhika , Zreiqat Hala
Published: October 2007

Calcium silicate (CaSiO3) is regarded as a potential bioactive material. However, its poor chemical stability and cytocompatibility limits its biological applications. The aim of this study is to incorporate Titanium (Ti) into CaSiO3 to produce a ceramic with improved chemical stability and biological properties. Sphene (CaTiSiO5) ceramics were prepared by sintering sol–gel‐derived CaTiSiO5 powder compacts and their chemical stability was assessed by measuring the ions released and weight loss after soaking CaTiSiO5 in simulating body fluid for 1, 3, 7, and 14 days. Results indicated that CaTiSiO5 has a significantly improved chemical stability, compared with CaSiO3. The ability of CaTiSiO5 ceramics to support human bone‐derived cells (HBDC) attachment, proliferation, and differentiation was assessed using scanning electron microscopy, MTS, and alkaline phosphatase activity assays, respectively. CaTiSiO5 ceramics supported HBDC attachment and significantly enhanced their proliferation and differentiation, compared with CaSiO3 ceramics. Taken together, this study demonstrates that the newly developed CaTiSiO5 ceramics possess excellent chemical stability and bioactivity, suggesting their potential use in skeletal tissue regeneration and as coating onto currently available orthopedic/dental implants. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Maintaining bioactivity of NGF for controlled release from PLGA using PEG
Authors: Johnson Philip J. , Skornia Stacy L. , Stabenfeldt Sarah E. , Willits Rebecca Kuntz
Published: October 2007

The goal of this work was to investigate methods to retain bioactivity of nerve growth factor (NGF) after encapsulation in poly(lactic‐co‐glycolic acid) (PLGA) discs for controlled release. Poly(ethylene glycol) (PEG) was chosen as a porogen not only to control the release rate of NGF but also because it has been used to help maintain bioactivity of molecules in organic solvents. NGF and PEG were encapsulated in PLGA via standard dissolution–evaporation techniques with methylene chloride as the solvent. Morita et al. (Pharm Res 2000; 17:1367–1373) indicated that colyophilization of PEG and bioactive factors before exposure to organic solvents increased the retention of bioactivity. Therefore, various PEG:NGF mass ratios were colyophilized before encapsulation within PLGA to examine retained activity of NGF. When PEG was not colyophilized before encapsulation, NGF activity was lost during the fabrication process. In contrast, colyophilization of PEG and NGF supported retention of NGF activity during the entire fabrication process. The amount of PEG encapsulated was the dominating factor in the rate of NGF release regardless of the fabrication method. These results demonstrate the usefulness of PEG in both acting as a porogen to modulate release and aiding in the retention of activity of NGF. This process may be extended to other methods to enhance activity of growth factors after exposure to organic solvents. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Development and characterization of a rabbit alveolar bone nonhealing defect model
Authors: Young Simon , Bashoura Alex G. , Borden Timothy , Baggett L. Scott , Jansen John A. , Wong Mark , Mikos Antonios G.
Published: October 2007

The aim of this study was to develop an easily accessible and reproducible, nonhealing alveolar bone defect in the rabbit mandible. Twenty‐four adult male New Zealand white rabbits underwent unilateral mandibular defect surgery. Two types of defect in the premolar/molar region were compared: (1) a 10‐mm “full thickness” cylindrical defect removing both cortical plates and the intervening trabecular bone and tooth roots; (2) a 10‐mm “partial thickness” cylindrical defect removing only the lateral bony cortex, trabecular bone, and tooth roots. Both types of defect were examined at 0, 8, and 16 weeks using histology and/or microcomputed tomography to determine the quality and quantity of bone formation. The partial thickness defect displayed significant bone fill at 8 weeks (86.9% ± 10.8%), and complete regeneration of bony contours and bridging by 16 weeks. In contrast, the full thickness defect was never able to bridge itself and displayed no significant difference in bone regeneration between the 8‐week (61.5% ± 3.7%) and 16‐week (55.1% ± 18.5%) time points. These results indicate that a nonhealing defect can be created with a 10‐mm bicortical cylindrical ostectomy placed in the premolar/molar region of the rabbit mandible, demonstrating the potential of this animal model as a test bed for mandibular biomaterials and tissue‐engineering constructs. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
β‐TCP microporosity decreases the viability and osteoblast differentiation of human bone marrow stromal cells
Authors: Isaac Juliane , Hornez Jean‐Christophe , Jian Ding , Descamps Michel , Hardouin Pierre , Magne David
Published: October 2007

Association of osteoprogenitor cells to calcium phosphate ceramics is currently under intense investigation, for its considered ability to induce bone formation and therefore to allow the successful repair of large bone defects. However, if the first experimental and clinical studies provided promising results, lack of new bone formation has been reported in a large number of animal experiments. In this context and since it has been reported that in some conditions, calcium phosphate ceramic microstructure induces ectopic bone formation, we investigated the effects of ceramic microporosity on the behavior of osteoprogenitor cells for the development of hybrid materials. Human bone marrow stromal cells (BMSCs) were seeded on β‐tricalcium phosphate (TCP) ceramics with 0, 25, or 45% microporosity and cell adhesion, viability, and osteoblastic differentiation have been studied for three weeks. Cell counts, measurement of MTS conversion, and LDH activity indicated that microporosity decreased the viability of BMSCs in a time and rate‐dependent manner. In addition, microporosity inhibited osteoblastic differentiation as compared with nonmicroporous ceramics, as revealed by decreased alkaline phosphatase activity and osteocalcin secretion. Results of this in vitro study therefore highlight a negative role for β‐TCP microporosity in the behavior of human osteoprogenitor cells. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Synthesis, self‐association and chiroselectivity of isotopically labeled trianglamine macrocycles in the ion trap mass spectrometer
Authors: Kuhnert Nikolai , Le‐Gresley Adam , Nicolau Daniel C. , Lopez‐Periago Ana
Published: October 2007

The synthesis and self‐association of chiral isotopically labeled trianglamine macrocycles under electrospray mass spectrometer conditions in an ion trap are described. A moderate diastereoselectivity in the self‐association process was observed providing a synthetic model system for the investigation of chiral self‐association in the gas phase. The first non‐covalently bound dimer exclusively bonded through aromatic–aromatic interactions was observed in the gas phase. Evidence for self‐association in solution was observed by diffusion nuclear magnetic resonance spectroscopy. Copyright © 2007 John Wiley & Sons, Ltd.
Utilization of diffusion tensor tractography in combination with spatial normalization to assess involvement of the corticospinal tract in capsular/pericapsular stroke: Feasibility and clinical implications
Authors: Kunimatsu Akira , Itoh Daisuke , Nakata Yasuhiro , Kunimatsu Natsuko , Aoki Shigeki , Masutani Yoshitaka , Abe Osamu , Yoshida Mariko , Minami Manabu , Ohtomo Kuni
Published: October 2007

Purpose

To investigate the feasibility of using spatial normalization in combination with diffusion tensor (DT) corticospinal tractography to assess corticospinal tract (CST) involvement in capsular or pericapsular stroke.

Materials and Methods

Corticospinal tractograms were created and segmented out using DT imaging (DTI) data from 10 normal volunteers. After spatial normalization was achieved with statistical parametric mapping (SPM), the whole ensemble of tractograms was used as a map of the CST. This was overlaid on the infarction site, which had also been spatially normalized from isotropic diffusion‐weighted (DW) images of 14 patients with small symptomatic capsular or pericapsular infarction. We evaluated the extent of CST involvement within the infarction site. Differences were sought in relation to recovery of muscle strength.

Results

The CST was engulfed by the infarction in all patients. Muscle strength recovery occurred in 10 of the 14 patients. The extent of cross‐sectional and longitudinal involvement in the infarction site was related to motor recovery (P = 0.041).

Conclusion

An evaluation of the involvement of the CST in cases of capsular or pericapsular infarction utilizing DT fiber tractography in combination with spatial normalization was found to be feasible as it clearly visualized the extent of CST involvement consistent with the symptom. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
MRI evaluation of microvascular obstruction in experimental reperfused acute myocardial infarction using a T1 and T2 preparation pulse sequence
Authors: Yang Yuesong , Foltz Warren D. , Graham John J. , Detsky Jay S. , Dick Alexander J. , Wright Graham A.
Published: October 2007

Purpose

To investigate a T1 and T2 preparation pulse sequence to evaluate microvascular obstruction (MO) in a porcine model of reperfused acute myocardial infarction (AMI).

Materials and Methods

A total of 14 pigs with reperfused AMI underwent MRI examinations at baseline and three to four hours after reperfusion. MRI scans included a left ventricular functional study, T1 and T2 measurement on a 1.5T MRI system. At reperfusion, first‐pass myocardial perfusion (FPMP) images were obtained after bolus injection of gadopentetate dimeglumine followed by an intravenous drip. Delayed contrast‐enhanced MRI (DE‐MRI) and T1 measurements were performed 30 and 45 minutes, respectively, after the bolus, during a constant infusion of gadopentetate dimeglumine.

Results

In 11 pigs MO was hypoenhanced in FPMP and DE‐MRI. In later T1 preparation difference images postcontrast, MO was hyperenhanced while delayed hyperenhanced (DHE) regions appeared dark. MO areas on DE‐MRI and T1 images were comparable. T1 reduction (%) postcontrast in MO was small compared to measurements from DHE regions (P < 0.0001) and similar to those from control segments (P = 0.66). Precontrast T1 and T2 values at reperfusion from MO and DHE regions were larger than in control regions.

Conclusion

Using T1 preparation under a constant gadopentetate dimeglumine (Gd‐DTPA) infusion, delayed imaging at 30 to 45 minutes demonstrates MO as a positive contrast with larger T1 values. Elevated T1 and T2 values in MO precontrast may also help to differentiate them from both control and DHE regions. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Comparison of flow patterns in ascending aortic aneurysms and volunteers using four‐dimensional magnetic resonance velocity mapping
Authors: Hope Thomas A. , Markl Michael , Wigström Lars , Alley Marcus T. , Miller D. Craig , Herfkens Robert J.
Published: October 2007

Purpose

To determine the difference in flow patterns between healthy volunteers and ascending aortic aneurysm patients using time‐resolved three‐dimensional (3D) phase contrast magnetic resonance velocity (4D‐flow) profiling.

Materials and Methods

4D‐flow was performed on 19 healthy volunteers and 13 patients with ascending aortic aneurysms. Vector fields placed on 2D planes were visually graded to analyze helical and retrograde flow patterns along the aortic arch. Quantitative analysis of the pulsatile flow was carried out on manually segmented planes.

Results

In volunteers, flow progressed as follows: an initial jet of blood skewed toward the anterior right wall of the ascending aorta is reflected posterolaterally toward the inner curvature creating opposing helices, a right‐handed helix along the left wall and a left‐handed helix along the right wall; retrograde flow occurred in all volunteers along the inner curvature between the location of the two helices. In the aneurysm patients, the helices were larger; retrograde flow occurred earlier and lasted longer. The average velocity decreased between the ascending aorta and the transverse aorta in volunteers (47.9 mm/second decrease, P = 0.023), while in aneurysm patients the velocity increased (145 mm/second increase, P < 0.001).

Conclusion

Dilation of the ascending aorta skews normal flow in the ascending aorta, changing retrograde and helical flow patterns. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Quantitative in vivo proton MR spectroscopic evaluation of the irradiated rat brain
Authors: Atwood Todd , Robbins Mike E. , Zhu Jian‐Ming
Published: October 2007

Purpose

To investigate if in vivo localized proton magnetic resonance spectroscopy (MRS) can detect putative metabolic changes in the irradiated rat brain and quantitatively measure brain metabolite changes in this model.

Materials and Methods

A total of 20 adult male Fischer 344 rats were exposed to a fractionated regimen of whole brain irradiation (WBI) (total 45 Gy, given as five Gy fractions, twice per week for 4.5 weeks); 10 control rats received sham irradiation. A total of 52 weeks after WBI, all animals were subjected to high‐resolution MRI and in vivo proton MRS to determine structural and brain metabolite changes. Brain metabolites were measured by using single‐voxel MRS. Quantitative analysis of detectable metabolites was performed by using the spectral analysis method, LCModel.

Results

Significant differences in brain metabolite concentrations were detected in rat brains irradiated with a clinically relevant fractionated radiotherapy regimen in 52 weeks, in comparison to age‐matched sham‐irradiated rats.

Conclusion

These findings indicate that quantitative in vivo MRS may serve as a sensitive imaging tool to noninvasively detect neurochemical changes in the irradiated brain. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Real‐time MR imaging of myocardial regional function using strain‐encoding (SENC) with tissue through‐plane motion tracking
Authors: Ibrahim El‐Sayed H. , Stuber Matthias , Fahmy Ahmed S. , Abd‐Elmoniem Khaled Z. , Sasano Tetsuo , Abraham M. Roselle , Osman Nael F.
Published: October 2007

Purpose

To implement real‐time myocardial strain‐encoding (SENC) imaging in combination with tracking the tissue displacement in the through‐plane direction.

Materials and Methods

SENC imaging was combined with the slice‐following technique by implementing three‐dimensional (3D) selective excitation. Certain adjustments were implemented to reduce scan time to one heartbeat. A total of 10 volunteers and five pigs were scanned on a 3T MRI scanner. Spatial modulation of magnetization (SPAMM)‐tagged images were acquired on planes orthogonal to the SENC planes for comparison. Myocardial infarction (MI) was induced in two pigs and the resulting SENC images were compared to standard delayed‐enhancement (DE) images.

Results

The strain values computed from SENC imaging with slice‐following showed significant difference from those acquired without slice‐following, especially during systole (P < 0.01). The strain curves computed from the SENC images with and without slice‐following were similar to those computed from the orthogonal SPAMM images, with and without, respectively, tracking the tag line displacement in the strain direction. The resulting SENC images showed good agreement with the DE images in identifying MI in infarcted pigs.

Conclusion

Correction of through‐plane motion in real‐time cardiac functional imaging is feasible using slice‐following. The strain measurements are more accurate than conventional SENC measurements in humans and animals, as validated with conventional MRI tagging. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Multiparametric differentiation of posterior fossa tumors in children using diffusion‐weighted imaging and short echo‐time 1H‐MR spectroscopy
Authors: Schneider J.F. , Confort‐Gouny S. , Viola A. , Le Fur Y. , Viout P. , Bennathan M. , Chapon F. , Figarella‐Branger D. , Cozzone P. , Girard N.
Published: October 2007

Purpose

To assess the combined value of diffusion‐weighted imaging (DWI) and proton magnetic resonance spectroscopy (1H‐MRS) in differentiating medulloblastoma, ependymoma, pilocytic astrocytoma, and infiltrating glioma in a pediatric population.

Materials and Methods

A total of 17 children with untreated posterior fossa tumors (seven medulloblastoma, four infiltrating glioma, two ependymoma, and four pilocytic astrocytoma), were investigated with conventional MRI, DWI, and MRS using a single‐voxel technique. Within the nonnecrotic tumor core, apparent diffusion coefficient (ADC) values using a standardized region of interest (ROI) were retrieved. Quantification of water signal and analysis of metabolite signals from MRS measurements in the same tumorous area were reviewed using multivariant linear discriminant analysis.

Results

Combination of ADC values and metabolites, which were normalized using water as an internal standard, allowed discrimination between the four tumor groups with a likelihood below 1 × 10–9. Positive predictive value was 1 in all cases. Tumors could not be discriminated when using metabolite ratios or ADC values alone, nor could they be differentiated using creatine (Cr) as an internal reference even in combination with ADC values.

Conclusion

Linear discriminant analysis using DWI and MRS using water as internal reference, fully discriminates the four most frequent posterior fossa tumors in children. J. Magn. Reson. Imaging. © 2007 Wiley‐Liss, Inc.
MRI of ischemic stroke in canines: Applications for monitoring intraarterial thrombolysis
Authors: Harris Ashley D. , Kosior Jayme C. , Ryder Ronda C. , Andersen Linda B. , Hu William Y. , Hudon Mark , Morrish William H. , Sevick Robert J. , Wong John , Frayne Richard
Published: October 2007

Purpose

To describe a canine embolic stroke model that is appropriate for endovascular procedure evaluations and develop local cerebral blood flow (CBF) maps to monitor the progression of stroke and thrombolysis. In the future, MR may displace X‐ray imaging in some endovascular procedures, such as intraarterial (IA) thrombolysis for stroke therapy, due to increased monitoring capabilities. For MR to attain its full potential in endovascular therapy, the development of appropriate disease models and monitoring techniques is essential.

Materials and Methods

The canine stroke model uses an injection of autologous clot to produce ischemic and infarcted tissue and produces a range of stroke severities within the anterior cerebral circulation. Local CBF maps were formed by using the catheter that would be in place to deliver the thrombolytic agent for treatment to deliver the gadolinium‐based contrast agent for perfusion imaging.

Results

After the injection of clot, changes on imaging were consistent with the progression of ischemic stroke. Local CBF maps showed perfusion changes with stroke progression and treatment.

Conclusion

We successfully demonstrate the progression of ischemic stroke in the canine to mimic the progression of human stroke. CBF maps to show local perfusion characteristics show great potential in the evaluation of stroke therapy. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Improved tumor vascular function following high‐dose epidermal growth factor receptor tyrosine kinase inhibitor therapy
Authors: Moasser Mark M. , Wilmes Lisa J. , Wong Ching Hang , Aliu Sheye , Li Ka‐Loh , Wang Donghui , Hom Yun Kit , Hann Byron , Hylton Nola M.
Published: October 2007

Purpose

To determine if inhibitors of the human growth factor receptor (HER) family can be used to enhance tumor vascular permeability and perfusion and optimize the efficacy of cytotoxic chemotherapeutics. Poor tumor vascular function limits the delivery and efficacy of cancer chemotherapeutics and HER family tyrosine kinases mediate tumor‐endothelial signaling in both of these compartments.

Materials and Methods

BT474 human breast cancer tumors were established in mice and the biologic effects of the HER tyrosine kinase inhibitor (TKI) gefitinib on tumor vascular function was determined by dynamic contrast‐enhanced MRI (DCE‐MRI), and on tumor vascular architecture and perfusion by immunofluorescence microscopy.

Results

A brief dose of gefitinib enhances the antitumor activity of paclitaxel in vivo but not in cell culture, suggesting that its chemoenhancing activity involves the in vivo microenvironment. A brief high dose of gefitinib induces a decrease in endothelial transfer constant (Kps) and a concomitant increase in tumor fractional plasma volume (fPV). These changes are accompanied by a rapid reduction in tumor volume, likely due to decreased tumor edema, and modestly improved tumor vascular architecture and perfusion on microscopy.

Conclusion

These data suggest that HER family TKIs have the potential to optimize the tumor microenvironment for delivery of cytotoxic chemotherapeutics. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Black‐blood imaging of the human heart using rapid stimulated echo acquisition mode (STEAM) MRI
Authors: Karaus Alexander , Merboldt Klaus‐Dietmar , Graessner Joachim , Frahm Jens
Published: October 2007

Purpose

To develop a rapid stimulated echo acquisition mode (STEAM) MRI technique for “black‐blood” imaging of the human heart that overcomes the single‐slice limitation and partially compromised blood suppression associated with double inversion‐recovery techniques.

Materials and Methods

Black‐blood multislice images of the heart along anatomic orientations and triggered to end diastole were obtained from healthy human subjects at 3T using rapid STEAM MRI sequences with five‐eighths partial Fourier encoding and variable flip angles. Single‐shot STEAM images at 2.5 × 2.5 mm2 in‐plane resolution and 6‐mm section thickness were recorded in 230 msec from individual heartbeats. Improved signal‐to‐noise ratio (SNR) and higher spatial resolution of 2.0 × 2.0 mm2 and 1.5 × 1.5 mm2 were achieved by segmented multishot STEAM MRI with interleaved k‐space acquisitions (160 msec each) from several heartbeats. In a single breathhold covering 18 heartbeats selected applications employed either three segments with six sections or six segments with three sections.

Results

Because stimulated echoes (STEs) dephase signals from moving spins, rapid STEAM images are free from blood signal contamination. The method offers a flexible tradeoff between spatial resolution, imaging speed (i.e., number of segments), and volume coverage (i.e., number of sections).

Conclusion

Rapid STEAM MRI of the heart emerges as a simple technique for multislice imaging of the myocardial wall with efficient flow suppression. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
New designer drugs N‐(1‐phenylcyclohexyl)‐2‐ethoxyethanamine (PCEEA) and N‐(1‐phenylcyclohexyl)‐2‐methoxyethanamine (PCMEA): Studies on their metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric techniques
Authors: Sauer Christoph , Peters Frank T. , Staack Roland F. , Fritschi Giselher , Maurer Hans H.
Published: October 2007

Studies are described on the metabolism and the toxicological detection of the phencyclidine‐derived designer drugs N‐(1‐phenylcyclohexyl)‐2‐ethoxyethanamine (PCEEA) and N‐(1‐phenylcyclohexyl)‐2‐methoxyethanamine (PCMEA) in rat urine using gas chromatographic/mass spectrometric (GC/MS) techniques. The identified metabolites indicated that PCEEA and PCMEA were transformed to the same metabolites by N‐dealkylation and O‐dealkylation partially followed by oxidation of the resulting alcohol to the respective carboxylic acid and hydroxylation of the cyclohexyl ring at different positions and combinations of those. Finally, aromatic hydroxylation of the O‐dealkylated metabolites was partially followed by hydroxylation of the cyclohexyl ring at different positions. All metabolites were partially excreted in conjugated form. The authors' systematic toxicological analysis (STA) procedure using full‐scan GC/MS after acid hydrolysis, liquid–liquid extraction and microwave‐assisted acetylation allowed the detection of an intake of a common drug users' dose both of PCEEA and PCMEA in rat urine. Assuming similar metabolism in humans, the STA should be suitable for proof of an intake of PCEEA and PCMEA in human urine, although their differentiation is not possible due to common metabolites. Copyright © 2007 John Wiley & Sons, Ltd.
Studies on alkaloids binding to GC‐rich human survivin promoter DNA using positive and negative ion electrospray ionization mass spectrometry
Authors: Wang Zhaofu , Guo Xinhua , Liu Zhiqiang , Cui Meng , Song Fengrui , Liu Shuying
Published: October 2007

Electrospray ionization mass spectrometry (ESI‐MS) was used to investigate the binding of 13 alkaloids to two GC‐rich DNA duplexes which are critical sequences in human survivin promoter. Negative ion ESI‐MS was first applied to screen the binding of the alkaloids to the duplexes. Six alkaloids (including berberine, jatrorrhizine, palmatine, reserpine, berbamine, and tetrandrine) show complexation with the target DNA sequences. Relative binding affinities were estimated from the negative ion ESI data, and the alkaloids show a binding preference to the duplex with higher GC content. Positive ion ESI mass spectra of the complexes were also recorded and compared with those obtained in negative ion mode. Only the 1 : 1 complex with berbamine was observed with lower abundance in the positive ion mass spectrum while complexes with the other alkaloids were absolutely absent. Collision‐induced dissociation (CID) experiments indicate that the complexes with the protoberberine alkaloids (berberine, jatrorrhizine, and palmatine) dissociate via base loss and covalent cleavage. In contrast, product ion spectra of the complexes with the alkaloids reserpine, berbamine, and tetrandrine show the predominant loss of a neutral alkaloid molecule, accompanied by base loss and covalent cleavage to a lesser extent. A comparison of the gas‐phase behaviors of complexes with the alkaloids to those with the traditional DNA binders has suggested an intercalative binding mode of these alkaloids to the target DNA duplexes. Copyright © 2007 John Wiley & Sons, Ltd.
Deletion of the STOP gene, a microtubule stabilizing factor, leads only to discrete cerebral metabolic changes in mice
Authors: Hanaya Ryosuke , Koning Estelle , Ferrandon Arielle , Schweitzer Annie , Andrieux Annie , Nehlig Astrid
Published: October 2007

In mice, deletion of the STOP protein leads to subtle anatomic changes and induces depleted synaptic vesicle pools, impaired synaptic plasticity, hyperdopaminergy, and major behavioral disorders alleviated by neuroleptics, hence leading to a schizophrenic‐like phenotype. In this study, we applied the quantitative autoradiographic [14C]2‐deoxyglucose technique to study to what extent the basal rate of cerebral glucose utilization in STOP‐knockout (STOP‐KO) mice occurs in regions where metabolic changes have been reported in schizophrenic patients. Studies were performed on wild‐type, heterozygous, and homozygous STOP‐KO mice (7–8 per group). Mice were implanted with femoral artery and vein catheters, and cerebral glucose utilization was quantified over 45 min. Compared with that in wild‐type mice, glucose utilization in STOP‐KO mice was significantly increased in the olfactory cortex, ventromedial and anterolateral hypothalamus, ventral tegmental area, and substantia nigra pars compacta. Nonsignificant increases, ranging between 9% and 19%, were recorded in the whole auditory system, CA1 pyramidal cell layer, and dorsal raphe. Glucose utilization was also significantly increased in heterozygous mice compared with that in wild‐type mice in olfactory cortex. These data might reflect hyperdopaminergic activity, olfactory deficits, and sleep disturbances in STOP‐KO mice that have also been reported in schizophrenic patients. © 2007 Wiley‐Liss, Inc.
Discoidin domain receptor 1 mediates collagen‐induced inflammatory activation of microglia in culture
Authors: Seo Min‐Chul , Kim Sangseop , Kim Sang‐Hyun , Zheng Long Tai , Park Eui Kyun , Lee Won‐Ha , Suk Kyoungho
Published: October 2007

Discoidin domain receptor 1 (DDR1) is a nonintegrin collagen receptor tyrosine kinase with an extracellular domain homologous to discoidin 1 of a soil‐living amoeba Dictyostelium discoideum. We have previously demonstrated that DDR1 mediates collagen‐induced nitric oxide production in J774A.1 murine macrophages. Because collagen is one of the main components of extracellular matrix in the central nervous system, we hypothesized that collagen also induces inflammatory activation of brain microglia, and DDR1 may mediate collagen‐induced microglial activation. Using BV‐2 mouse microglial cells and mouse primary microglial cultures, we have demonstrated that (1) collagen induces inflammatory activation of microglia as evidenced by production of nitric oxide, expression of inducible nitric oxide synthase, COX‐2, CD40, and matrix metalloproteinase–9; (2) DDR1 is expressed in microglia and is phosphorylated by collagen treatment; and (3) collagen‐induced microglial activation is abrogated by DDR1 blockade but not by integrin neutralization. We have further shown that p38 MAPK, c‐Jun N‐terminal kinase, and nuclear factor–kappa B are involved in the collagen‐DDR1‐induced microglial activation. Our results suggest that collagen can induce inflammatory activation of brain microglia and that DDR1 mediates this effect of collagen in an integrin‐independent manner. © 2007 Wiley‐Liss, Inc.
Calcium‐enriched goat milk, in comparison with similarly enriched cow milk, favours magnesium bioavailability in rats with nutritional ferropenic anaemia
Authors: Nestares Teresa , Díaz‐Castro Javier , Alférez María JM , López‐Aliaga Inmaculada , Barrionuevo Mercedes , Campos Margarita S
Published: October 2007

BACKGROUND: The effects of dietary consumption of goat or cow milk, normal or enriched with calcium (Ca), on magnesium (Mg) bioavailability was evaluated in rats with nutritional ferropenic anaemia. Control and iron‐deficient rats were fed for 14 days with iron‐normal diets containing either normal (5000 mg kg−1 diet) or high (10 000 mg kg−1 diet) Ca content.

RESULTS: The results shown that the goat milk diet gave the best results for digestive and metabolic utilization of Mg, both among the anaemic and the control group, with respect to the cow milk and standard diets. The most noteworthy result of Ca enrichment on the nutritive utilization of Mg is that it is less prejudicial in this respect when supplemented via goat milk than with cow milk or the standard diet.

CONCLUSION: The results demonstrate the beneficial effects of the goat milk, normal or with double Ca, on the nutritional utilization of Mg; therefore the consumption of this type of milk for people with nutritional ferropenic anaemia can be recommended. Copyright © 2007 Society of Chemical Industry
Hyperpolarized C‐13 spectroscopic imaging of the TRAMP mouse at 3T—Initial experience
Authors: Chen Albert P. , Albers Mark J. , Cunningham Charles H. , Kohler Susan J. , Yen Yi‐Fen , Hurd Ralph E. , Tropp James , Bok Robert , Pauly John M. , Nelson Sarah J. , Kurhanewicz John , Vigneron Daniel B.
Published: October 2007

The transgenic adenocarcinoma of mouse prostate (TRAMP) mouse is a well‐studied murine model of prostate cancer with histopathology and disease progression that mimic the human disease. To investigate differences in cellular bioenergetics between normal prostate epithelial cells and prostate tumor cells, in vivo MR spectroscopic (MRS) studies with non‐proton nuclei, such as 13C, in the TRAMP model would be extremely useful. The recent development of a method for retaining dynamic nuclear polarization (DNP) in solution permits high signal‐to‐noise ratio (SNR) 13C MRI or MRSI data to be obtained following injection of a hyperpolarized 13C agent. In this transgenic mouse study, this method was applied using a double spin‐echo (DSE) pulse sequence with a small‐tip‐angle excitation RF pulse, hyperbolic‐secant refocusing pulses, and a flyback echo‐planar readout trajectory for fast (10–14 s) MRSI of 13C pyruvate (pyr) and its metabolic products at 0.135 cm3 nominal spatial resolution. Elevated 13C lactate (lac) was observed in both primary and metastatic tumors, demonstrating the feasibility of studying cellular bioenergetics in vivo with DNP hyperpolarized 13C MRSI. Magn Reson Med, 2007. © 2007 Wiley‐Liss, Inc.
Obtaining blood oxygenation levels from MR signal behavior in the presence of single venous vessels
Authors: Sedlacik Jan , Rauscher Alexander , Reichenbach Jürgen R.
Published: October 2007

The MR signal decay in gradient echo sequences includes signal loss due to spin dephasing caused by static magnetic field inhomogeneities. This decay can be calculated for different geometries of the susceptibility distribution, such as spheres, cylinders, or cylinder networks. In particular, the model of an infinitely long cylinder is a good approximation for single straight blood vessels. Blood oxygenation and blood volume fraction are important parameters, which influence the signal in a characteristic way. In this work the signal decays for a single cylindrical vessel were investigated and evaluated in simulations, phantom measurements as well as in vivo measurements of small single veins in the human brain by using a 3D multiecho gradient echo sequence. Good agreement between simulations and phantom experiments was obtained for different experimental settings. Based on the simulations, physiologically consistent values of venous blood oxygenation level, Y, were extracted from the in vivo measurements of different veins and volunteers (Y = 0.55 ± 0.02). The methods ability to measure changes in venous blood oxygenation induced by carbogen breathing was demonstrated in one volunteer, where an increase from Y ≈ 0.5 to Y ≈ 0.7 was observed. Magn Reson Med 58:1035–1044, 2007. © 2007 Wiley‐Liss, Inc.