bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue equivalency of phantom materials for neutron dosimetry in proton therapy
Authors: Dowdell Stephen , Clasie Ben , Wroe Andrew , Guatelli Susanna , Metcalfe Peter , Schulte Reinhard , Rosenfeld Anatoly 
Published: November 2009

Purpose:Previous Monte Carlo and experimental studies involving secondary neutrons in proton therapy have employed a number of phantom materials that are designed to represent human tissue. In this study, the authors determined the suitability of common phantom materials for dosimetry of secondary neutrons, specifically for pediatric and intracranial proton therapy treatments.Methods:This was achieved through comparison of the absorbed dose and dose equivalent from neutrons generated within the phantom materials and various ICRP tissues. The phantom materials chosen for comparison were Lucite, liquid water, solid water, and A150 tissue equivalent plastic. These phantom materials were compared to brain, muscle, and adipose tissues.Results:The magnitude of the doses observed were smaller than those reported in previous experimental and Monte Carlo studies, which incorporated neutrons generated in the treatment head. The results show that for both neutron absorbed dose and dose equivalent, no single phantom material gives agreement with tissue within 5% at all the points considered. Solid water gave the smallest mean variation with the tissues out of field where neutrons are the primary contributor to the total dose.Conclusions:Of the phantom materials considered, solid water shows best agreement with tissues out of field.
Geometric feature‐based multimodal image registration of contrast‐enhanced cardiac CT with gated myocardial perfusion SPECT
Authors: Woo Jonghye , Slomka Piotr J. , Dey Damini , Cheng Victor Y. , Hong Byung‐Woo , Ramesh Amit , Berman Daniel S. , Karlsberg Ronald P. , Kuo C.‐C. Jay , Germano Guido 
Published: November 2009

Purpose:Cardiac computed tomography (CT) and single photon emission computed tomography (SPECT) provide clinically complementary information in the diagnosis of coronary artery disease (CAD). Fused anatomical and physiological data acquired sequentially on separate scanners can be coregistered to accurately diagnose CAD in specific coronary vessels.Methods:A fully automated registration method is presented utilizing geometric features from a reliable segmentation of gated myocardial perfusion SPECT (MPS) volumes, where regions of myocardium and blood pools are extracted and used as an anatomical mask to de‐emphasize the inhomogeneities of intensity distribution caused by perfusion defects and physiological variations. A multiresolution approach is employed to represent coarse‐to‐fine details of both volumes. The extracted voxels from each level are aligned using a similarity measure with a piecewise constant image model and minimized using a gradient descent method. The authors then perform limited nonlinear registration of gated MPS to adjust for phase differences by automatic cardiac phase matching between CT and MPS. For phase matching, they incorporate nonlinear registration using thin‐plate‐spline‐based warping. Rigid registration has been compared with manual alignment on 20 stress/rest MPS and coronary CTA data sets acquired from two different sites and five stress CT perfusion data sets. Phase matching was also compared to expert visual assessment.Results:As compared with manual alignment obtained from two expert observers, the mean and standard deviation of absolute registration errors of the proposed method for MPS were, , and for translation and , , and for rotation at site A and , , and for translation and , , and for rotation at site B. The results for CT perfusion were , , and for translation and , , and for rotation. The registration error shows that the proposed method achieves registration accuracy of less than 1 voxel misalignment. The proposed method was robust for different initializations in the range from to 70, to 70, and in the ‐, ‐, and ‐axes, respectively. Validation results of finding best matching phase showed that best matching phases were not different by more than two phases, as visually determined.Conclusions:The authors have developed a fast and fully automated method for registration of contrast cardiac CT with gated MPS which includes nonlinear cardiac phase matching and is capable of registering these modalities with accuracy in 87% of the cases.
An EPID based method for efficient and precise asymmetric jaw alignment quality assurance
Authors: Clews Luke , Greer Peter B. 
Published: November 2009

Purpose:The aim of this work was to investigate the use of amorphous silicon electronic portal imaging devices (EPIDs) for regular quality assurance of linear accelerator asymmetric jaw junctioning.Methods:The method uses the beam central axis position on the EPID measured to subpixel accuracy found from two EPID images with 180° opposing collimator angles. Individual zero jaw position (“half‐beam blocked”) images are then acquired and the jaw position precisely determined for each using penumbra interpolation. The accuracy of determining jaw position with the EPID method was measured by translating a block (simulating a jaw) by known distances, using a translation stage, and then measuring each translation distance with the EPID. To establish the utility of EPID based junction dose measurements, radiographic film measurements of junction dose maxima/minima as a function of jaw gap/overlap were made and compared to EPID measurements. Using the method, the long‐term stability of zero jaw positioning was assessed for four linear accelerators over a 1–1.5 yr time period. The stability at nonzero gantry angles was assessed over a shorter time period.Results:The accuracy of determining jaw translations with the method was within 0.14 mm found using the translation stage [standard deviation (SD) of 0.037 mm]. The junction doses measured with the EPID were different from film due to the nonwater equivalent EPID scattering properties and hence different penumbra profile. The doses were approximately linear with gap or overlap, and a correction factor was derived to convert EPID measured junction dose to film measured equivalent. Over a 1 yr period, the zero jaw positions at gantry zero position were highly reproducible with an average SD of 0.07 mm for the 16 collimator jaws examined. However, the average jaw positions ranged from −0.7 to 0.9 mm relative to central axis for the different jaws. The zero jaw position was also reproducible at gantry 90° position with 0.1 mm SD variation with the mean jaw position offset from the gantry zero position consistently by 0.3–0.4 mm for the jaws studied.Conclusions:The EPID based method is efficient and yields more precise data on linear accelerator jaw positioning and reproducibility than previous methods. The results highlight that zero jaw positions are highly reproducible to a level much smaller than the displayed jaw resolution and that there is a need for better methods to calibrate the jaw positioning.
Computer‐assisted extraction of intracranial aneurysms on 3D rotational angiograms for computational fluid dynamics modeling
Authors: Chang Herng‐Hua , Duckwiler Gary R. , Valentino Daniel J. , Chu Woei Chyn 
Published: November 2009

Purpose:Three‐dimensional rotational angiography (3DRA) is an evolving imaging procedure from traditional digital subtraction angiography and is gaining much interest for detecting intracranial aneurysms. Computational fluid dynamics (CFD) modeling plays an important role in understanding the biomechanical properties and in facilitating the prediction of aneurysm rupture. A successful computational study relies on an accurate description of the vascular geometry that is obtained from volumetric images.Methods:The authors propose a new aneurysm segmentation algorithm to facilitate the study of CFD. This software combines a region‐growing segmentation method with the 3D extension of a deformable contour based on a charged fluid model. A charged fluid model essentially consists of a set of charged elements that are governed by the nature of electrostatics. The approach requires no prior knowledge of anatomic structures and automatically segments the vasculature after the end‐user selects a vessel section in a plane image.Results:Experimental results on 15 cases indicate that aneurysm structures were effectively segmented and in good agreement with manual delineation outcomes. In comparison with the existing methods, the algorithm provided a much higher overlap index with respect to the ground truth. Furthermore, the outcomes of the proposed approach achieved a clean representation of vascular structures that is advantageous for hemodynamics analyses.Conclusions:A new aneurysm segmentation framework in an attempt to automatically segment vascular structures in 3DRA image volumes has been developed. The proposed algorithm demonstrated promising performance and unique characteristics to adequately segment aneurysms in 3DRA image volumes for further study in computational fluid dynamics.
Singular value decomposition based computationally efficient algorithm for rapid dynamic near‐infrared diffuse optical tomography
Authors: Gupta Saurabh , Yalavarthy Phaneendra K. , Roy Debasish , Piao Daqing , Vasu Ram M. 
Published: November 2009

Purpose:A computationally efficient algorithm (linear iterative type) based on singular value decomposition (SVD) of the Jacobian has been developed that can be used in rapid dynamic near‐infrared (NIR) diffuse optical tomography.Methods:Numerical and experimental studies have been conducted to prove the computational efficacy of this SVD‐based algorithm over conventional optical image reconstruction algorithms.Results:These studies indicate that the performance of linear iterative algorithms in terms of contrast recovery (quantitation of optical images) is better compared to nonlinear iterative (conventional) algorithms, provided the initial guess is close to the actual solution. The nonlinear algorithms can provide better quality images compared to the linear iterative type algorithms. Moreover, the analytical and numerical equivalence of the SVD‐based algorithm to linear iterative algorithms was also established as a part of this work. It is also demonstrated that the SVD‐based image reconstruction typically requires operations per iteration, as contrasted with linear and nonlinear iterative methods that, respectively, require and operations, with “” being the number of unknown parameters in the optical image reconstruction procedure.Conclusions:This SVD‐based computationally efficient algorithm can make the integration of image reconstruction procedure with the data acquisition feasible, in turn making the rapid dynamic NIR tomography viable in the clinic to continuously monitor hemodynamic changes in the tissue pathophysiology.
In Vivo
Assessment of the Antimicrobial Activity of a Calcium-Deficient Apatite Vancomycin Drug Delivery System in a Methicillin-Resistant
Staphylococcus aureus
Rabbit Osteomyelitis Experimental Model
Authors: Amador G. , Gautier H. , Le Mabecque V. , Miegeville A. F. , Potel G. , Bouler J.-M. , Weiss P. , Caillon J. , Jacqueline C. 
Published: November 2009

ABSTRACT

The antimicrobial activities of calcium-deficient apatite loaded with different concentrations (25, 100, and 500 μg/mg) of vancomycin as a filling biomaterial were evaluated in a methicillin-resistant
Staphylococcus aureus
(MRSA) rabbit acute osteomyelitis model. Bacterial counts in bone, bone marrow, and joint fluid samples treated with forms of the apatite were compared to those in tissue samples receiving a constant intravenous vancomycin infusion after 4 days. This study demonstrates that using a calcium-deficient apatite loaded with vancomycin dramatically decreases the bacterial counts in bone and marrow.
Population Pharmacokinetic Analysis of Vancomycin Using Serum Cystatin C as a Marker of Renal Function
Authors: Tanaka Akihiro , Aiba Tetsuya , Otsuka Takashi , Suemaru Katsuya , Nishimiya Tatsuya , Inoue Tomoyoshi , Murase Mitsuharu , Kurosaki Yuji , Araki Hiroaki 
Published: November 2009

ABSTRACT
We determined the population pharmacokinetics of vancomycin (VAN) using the glomerular filtration rate (GFR) estimated from the serum cystatin C concentration. We examined the predictive performance of the trough serum VAN concentration for determination of the initial dose by using a new model for the analysis of the population pharmacokinetic parameters. Data for 86 patients were used to estimate the values of the population pharmacokinetic parameters. Analysis with a nonlinear mixed-effects modeling program was done by using a one-compartment model. Data for 78 patients were used to evaluate the predictive performance of the new model for the analysis of population pharmacokinetic parameters. The estimated GFR values determined by using Hoek's formula correlated linearly with VAN clearance (VAN clearance [ml/min] = 0.825 × GFR). The mean volume of distribution was 0.864 (liters/kg). The interindividual variability of VAN clearance was 19.8%. The accuracy of the prediction determined by use of the new model was statistically better than that determined by use of the Japanese nomogram-based model because the 95% confidence interval (−3.45 to −1.38) of the difference in each value of the mean absolute error (−2.41) did not include 0. Use of the serum cystatin C concentration as a marker of renal function for prediction of serum VAN concentrations may be useful.
Mechanism of Entecavir Resistance of Hepatitis B Virus with Viral Breakthrough as Determined by Long-Term Clinical Assessment and Molecular Docking Simulation
Authors: Mukaide Motokazu , Tanaka Yasuhito , Shin-I Tadasu , Yuen Man-Fung , Kurbanov Fuat , Yokosuka Osamu , Sata Michio , Karino Yoshiyasu , Yamada Gotaro , Sakaguchi Kohsaku , Orito Etsuro , Inoue Manami , Baqai Sumbella , Lai Ching-Lung , Mizokami Masashi 
Published: November 2009

ABSTRACTThe mechanism by which entecavir resistance (ETVr) substitutions of hepatitis B virus (HBV) can induce breakthrough (BT) during ETV therapy is largely unknown. We conducted a cross-sectional study of 49 lamivudine (LVD)-refractory patients and 59 naïve patients with chronic hepatitis B. BT was observed in 26.8% of the LVD-refractory group during weeks 60 to 144 of ETV therapy. A line probe assay revealed ETVr substitutions only in the LVD-refractory group, i.e., in 4.9% of patients at baseline, increasing to 14.6%, 24.4%, and 44.8% at weeks 48, 96, and 144, respectively. Multivariate logistic regression analysis adjusted for age, gender, HBV DNA levels, and LVD resistance (LVDr) (L180M and M204V, but not M204I) indicated that T184 substitutions and S202G (not S202C) were a significant factor for BT (adjusted odds ratio [OR], 141.12, and 95% confidence interval [CI], 6.94 to 2,870.20; OR, 201.25, and 95% CI, 11.22 to 3608.65, respectively). Modeling of HBV reverse transcriptase (RT) by docking simulation indicated that a combination of LVDr and ETVr (T184L or S202G) was characterized by a change in the direction of the D205 residue and steric conflict in the binding pocket of ETV triphosphate (ETV-TP), by significantly longer minimal distances (2.2 Å and 2.1 Å), and by higher potential energy (−117 and −99.8 Kcal/mol) for ETV-TP compared with the wild type (1.3 Å; −178 Kcal/mol) and LVDr substitutions (1.5 Å; −141 Kcal/mol). Our data suggest that the low binding affinity of ETV-TP for the HBV RT, involving conformational change of the binding pocket of HBV RT by L180M, M204V plus T184L, and S202G, could induce BT.
Plasmodium falciparumMerozoite Surface Protein 1 (MSP-1)-MSP-3 Chimeric Protein: Immunogenicity Determined with Human-Compatible Adjuvants and Induction of Protective Immune Response
Authors: Mazumdar Suman , Mukherjee Paushali , Yazdani Syed Shams , Jain S. K. , Mohmmed Asif , Chauhan Virander Singh 
Published: November 2009

ABSTRACTA chimeric gene,MSP-Fu24, was constructed by genetically coupling immunodominant, conserved regions of the two leading malaria vaccine candidates,Plasmodium falciparummerozoite surface protein 1 (C-terminal 19-kDa region [PfMSP-119]) and merozoite surface protein 3 (11-kDa conserved region [PfMSP-311]). The recombinant MSP-Fu24protein was produced inEscherichia colicells and purified to homogeneity by a two-step purification process with a yield of ∼30 mg/liter. Analyses of conformational properties of MSP-Fu24using PfMSP-119-specific monoclonal antibody showed that the conformational epitopes of PfMSP-119that may be critical for the generation of the antiparasitic immune response remained intact in the fusion protein. Recombinant MSP-Fu24was highly immunogenic in mice and in rabbits when formulated with two different human-compatible adjuvants and induced an immune response against both PfMSP-119and PfMSP-311. Purified anti-MSP-Fu24antibodies showed invasion inhibition ofP. falciparum3D7 and FCR parasites, and this effect was found to be dependent on antibodies specific for the PfMSP-119component. The protective potential of MSP-Fu24was demonstrated byin vitroparasite growth inhibition using an antibody-dependent cell inhibition (ADCI) assay with anti-MSP-Fu24antibodies. Overall, the antiparasitic activity was mediated by a combination of growth-inhibitory antibodies generated by both the PfMSP-119and PfMSP-311components of the MSP-Fu24protein. The antiparasitic activities elicited by anti-MSP-Fu24antibodies were comparable to those elicited by antibodies generated with immunization with a physical mixture of two component antigens, PfMSP-119and PfMSP-311. The fusion protein induces a protective immune response with human-compatible adjuvants and may form a part of a multicomponent malaria vaccine.
Infection of Mast Cells with Live Streptococci Causes a Toll-Like Receptor 2- and Cell-Cell Contact-Dependent Cytokine and Chemokine Response
Authors: Rönnberg Elin , Guss Bengt , Pejler Gunnar 
Published: November 2009

ABSTRACTMast cells (MCs) are strongly implicated in immunity toward bacterial infection, but the molecular mechanisms by which MCs contribute to the host response are only partially understood. We addressed this issue by examining the direct effects of a Gram-positive pathogen,Streptococcus equi, on bone marrow-derived MCs (BMMCs). Ultrastructural analysis revealed extensive formation of dilated rough endoplasmic reticulum in response to bacterial infection, indicating strong induction of protein synthesis. However, the BMMCs did not show signs of extensive degranulation, and this was supported by only slow release of histamine in response to infection. Coculture of live bacteria with BMMCs caused a profound secretion of CCL2/MCP-1, CCL7/MCP-3, CXCL2/MIP-2, CCL5/RANTES, interleukin-4 (IL-4), IL-6, IL-12, IL-13, and tumor necrosis factor alpha, as shown by antibody-based cytokine/chemokine arrays and/or enzyme-linked immunosorbent assay. In contrast, heat-inactivated bacteria caused only minimal cytokine/chemokine release. The cytokine/chemokine responses were substantially attenuated in Toll-like receptor 2-deficient BMMCs and were strongly dependent on cell-cell contacts between bacteria and BMMCs. Gene chip microarray analysis confirmed a massively upregulated expression of the genes coding for the secreted cytokines and chemokines and also identified a pronounced upregulation of numerous additional genes, including transcription factors, signaling molecules, and proteases. Together, the present study outlines MC-dependent molecular events associated with Gram-positive infection and thus provides an advancement in our understanding of how MCs may contribute to host defense toward bacterial insults.
Molecular and mechano-biology of collagen gel contraction mediated by human MG-63 cells: involvement of specific intracellular signaling pathways and the cytoskeleton
Authors: Parreno Justin , Hart David A. 
Published: November 2009

Culture of human osteoblast-like MG-63 cells within collagen gels results in the generation of intrinsic stress. Release of such collagen gels from attachment results in gel contraction and enhanced MMP-1, MMP-3, and α2 integrin mRNA levels. To understand the potential role of microtubules and signaling pathways involved in MG-63 cell-mediated contraction and gene expression, cells were cultured in collagen gels. After 24 h collagen gels were released, then immediately treated with nocodazole or specific protein kinase inhibitors. Contraction was assessed, RNA isolated, and real-time PCR analysis performed. Treatment with high concentrations of a microtubule depolymerization agent, nocodazole, enhanced early contraction and led to elevated mRNA levels for MMP-3, whereas low concentrations inhibited contraction at later time points and did not affect mRNA levels. ROCK inhibitor treatment (Y27632) inhibited collagen gel contraction and led to depressed mRNA levels. The ERK1/2 inhibitor U0126 did not affect contraction, but treatment led to depressed MMP-1, MMP-3, and α2 mRNA levels. The p38MAPK inhibitor SB203580 modestly affected contraction, but did not affect mRNA levels. These results suggest the potential role of cytoskeletal integrity and multiple kinase signaling pathways in specific bone-remodeling events.
Ameliorating effects of cloperastine on dysfunction of the urinary bladder caused by cerebral infarction in conscious rats
Authors: Yamamoto Gen , Soeda Fumio , Shirasaki Tetsuya , Takahama Kazuo 
Published: November 2009

We investigated the effects of the centrally acting antitussives dextromethorphan and cloperastine on urinary bladder dysfunction 24 h after cerebral infarction in rats using the cystometry technique. First, cystometrography was performed in conscious male Sprague–Dawley rats. Cerebral infarction was then induced by occlusion of the left middle cerebral artery. Twenty-four hours after cerebral infarction, the effect of each drug on micturition disorder was estimated for 5 parameters: bladder capacity, maximum voiding pressure, micturition latency, flow rate, and urethral resistance. Cerebral infarction markedly reduced bladder capacity, micturition latency, and flow rate and increased urethral resistance. After cerebral infarction, intravenous dosing of saline had no effect on these parameters. Dextromethorphan (20 mg/kg) and cloperastine (2.5 and 5.0 mg/kg) at antitussive effective doses significantly increased bladder capacity and micturition latency. Unlike dextromethorphan, cloperastine ameliorated decreases in flow rate and increases in urethral resistance caused by cerebral infarction. These results suggest that cloperastine may have therapeutic value for the treatment of disorders of the micturition reflex associated with cerebral infarction, and that the drug may become a base compound from which to develop more active drugs for such disorders.