bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of 3D volumetric image registration based on CT, MR and PET/CT phantom experiments
Authors: Li Guang , Xie Huchen , Ning Holly , Citrin Deborah , Capala Jacek , Maass‐Moreno Roberto , Guion Peter , Arora Barbara , Coleman Norman , Camphausen Kevin , Miller Robert W. 
Published: December 2008

Registration is critical for image‐based treatment planning and image‐guided treatment delivery. Although automatic registration is available, manual, visual‐based image fusion using three orthogonal planar views (3P) is always employed clinically to verify and adjust an automatic registration result. However, the 3P fusion can be time consuming, observer dependent, as well as prone to errors, owing to the incomplete 3‐dimensional (3D) volumetric image representations. It is also limited to single‐pixel precision (the screen resolution). The 3D volumetric image registration (3DVIR) technique was developed to overcome these shortcomings. This technique introduces a 4th dimension in the registration criteria beyond the image volume, offering both visual and quantitative correlation of corresponding anatomic landmarks within the two registration images, facilitating a volumetric image alignment, and minimizing potential registration errors. The 3DVIR combines image classification in real‐time to select and visualize a reliable anatomic landmark, rather than using all voxels for alignment. To determine the detection limit of the visual and quantitative 3DVIR criteria, slightly misaligned images were simulated and presented to eight clinical personnel for interpretation. Both of the criteria produce a detection limit of 0.1 mm and 0.1°. To determine the accuracy of the 3DVIR method, three imaging modalities (CT, MR and PET/CT) were used to acquire multiple phantom images with known spatial shifts. Lateral shifts were applied to these phantoms with displacement intervals of . The accuracy of the 3DVIR technique was determined by comparing the image shifts determined through registration to the physical shifts made experimentally. The registration accuracy, together with precision, was found to be: for CT/CT images, for MR/MR images, and for PET/CT images. This accuracy is consistent with the detection limit, suggesting an absence of detectable systematic error. This 3DVIR technique provides a superior alternative to the 3P fusion method for clinical applications.PACS numbers: 87.57.nj, 87.57.nm, 87.57.‐N, 87.57.‐s
Rotational total skin electron irradiation with a linear accelerator
Authors: Reynard Eric P. , Evans Michael D.C. , Devic Slobodan , Parker William , Freeman Carolyn R. , Roberge David , Podgorsak Ervin B. 
Published: December 2008

The rotational total skin electron irradiation (RTSEI) technique at our institution has undergone several developments over the past few years. Replacement of the formerly used linear accelerator has prompted many modifications to the previous technique. With the current technique, the patient is treated with a single large field while standing on a rotating platform, at a source‐to‐surface distance of 380 cm. The electron field is produced by a Varian 21EX linear accelerator using the commercially available 6 MeV high dose rate total skin electron mode, along with a custom‐built flattening filter. Ionization chambers, radiochromic film, and MOSFET (metal oxide semiconductor field effect transistor) detectors have been used to determine the dosimetric properties of this technique. Measurements investigating the stationary beam properties, the effects of full rotation, and the dose distributions to a humanoid phantom are reported. The current treatment technique and dose regimen are also described.PACS numbers: 87.55.ne, 87.53.Hv, 87.53.Mr
Compensator‐based intensity‐modulated radiation therapy for malignant pleural mesothelioma post extrapleural pneumonectomy
Authors: Javedan Khosrow , Stevens Craig W. , Forster Kenneth M. 
Published: December 2008

The present work investigated the potential of compensator‐based intensity‐modulated radiation therapy (CB‐IMRT) as an alternative to multileaf collimator (MLC)–based intensity‐modulated radiation therapy (IMRT) to treat malignant pleural mesothelioma (MPM) post extrapleural pneumonectomy.Treatment plans for 4 right‐sided and 1 left‐sided MPM post‐surgery cases were generated using a commercial treatment planning system, XIO/CMS (Computerized Medical Systems, St. Louis, MO). We used a 7‐gantry‐angle arrangement with 6 MV beams to generate these plans. The maximum required field size was . We evaluated IMRT plans with brass compensators (•Decimal, Sanford, FL) by examining isodose distributions, dose–volume histograms, metrics to quantify conformal plan quality, and homogeneity. Quality assurance was performed for one of the compensator plans.Conformal dose distributions were achieved with CB‐IMRT for all 5 cases, the average planning target volume (PTV) coverage being 95.1% of the PTV volume receiving the full prescription dose. The average lung (volume of lung receiving 20 Gy) was 1.8%, the mean lung dose was 6.7 Gy, and the average contralateral kidney was 0.6%. The average liver dose was 34.0% for the right‐sided cases and 10% for the left‐sided case. The average monitor units (MUs) per fraction were 980 MUs for the 45‐Gy prescriptions (mean: 50 Gy) and 1083 MUs for the 50‐Gy prescriptions (mean: 54 Gy).Post surgery, CB‐IMRT for MPM is a feasible IMRT technique for treatment with a single isocenter. Compensator plans achieved dose objectives and were safely delivered on a Siemens Oncor machine (Siemens Medical Solutions, Malvern, PA). These plans showed acceptably conformal dose distributions as confirmed by multiple measurement techniques. Not all linear accelerators can deliver large‐field MLC‐based IMRT, but most can deliver a maximum conformal field of . It is possible and reasonable to deliver IMRT with compensators for fields this size with most conventional linear accelerators.PACS numbers: 87.56.ng, 87.56.N, 87.55.D, 87.55.dk
An empirical model of electronic portal imager response implemented within a commercial treatment planning system for verification of intensity‐modulated radiation therapy fields
Authors: Khan Rao F.H. , Ostapiak Orest Z. , Szabo Joe J. 
Published: December 2008

Quality assurance (QA) of an intensity‐modulated radiation therapy (IMRT) plan is more complex than that of a conventional plan. To improve the efficiency of QA, electronic portal imaging devices (EPIDs) can be used. The major objective of the present work was to use a commercial treatment planning system to model EPID response for the purpose of pre‐treatment IMRT dose verification.Images were acquired with an amorphous silicon flat panel portal imager (aS500: Varian Medical Systems, Palo Alto, CA) directly irradiated with a 6‐MV photon beam from a Clinac 21EX linear accelerator (Varian Medical Systems). Portal images were acquired for a variety of rectangular fields, from which profiles and relative output factors were extracted. A dedicated machine model was created using the physics tools of the Pinnacle3 (Philips Medical Systems, Madison, WI) treatment planning system to model the data. Starting with the known photon spectrum and assuming an effective depth of 7 cm, machine model parameters were adjusted to best fit measured profile and output factors. The machine parameters of a second model, which assumed a 0.8 MeV monoenergetic photon spectrum and an effective depth in water of 3 cm, were also optimized. The second EPID machine model was used to calculate planar dose maps of simple geometric IMRT fields as well as a 9‐field IMRT plan developed for clinical trials credentialing purposes.The choice of energy and depth for an EPID machine model influenced the best achievable fit of the optimized machine model to the measured data. When both energy and depth were reduced by a significant amount, a better overall fit was achieved. In either case, the secondary source size and strength could be adjusted to give reasonable agreement with measured data. The gamma evaluation method was used to compare planar dose maps calculated using the second EPID machine model with the EPID images of small IMRT fields. In each case, more than 95% of points fell within 3% of the maximum dose or 3 mm distance to agreement. These results are slightly poorer than those obtained using an ion chamber array, which confirms agreement to within 2% of the maximum dose or 2 mm distance to agreement for all points within these fields.PACS numbers: 87.55Qr, 87.56.Fc
A plesiotherapy technique for the post‐operative treatment of skin cancer using Ir192 microSelectron.
Authors: Abatzoglou Ioannis , Tsoutsou Pelagia , Koukourakis Michael I. 
Published: December 2008

We describe a technique of postoperative irradiation of skin cancer using plesiotherapy with Ir192 high dose rate microSelectron afterloading system (Nucletron, Veenendaal, Netherlands). The clinically defined area is drawn on the skin and the flexible ‘skin applicator’ is then orientated so that the drawn skin area is encompassed within the catheter defined surface. Using a thin pewter wire, the skin drawn area is copied on the air‐adjacent surface of the applicator. Ex vivo CT simulation follows. The data are then transferred to the radiotherapy planning computer and the catheters are virtually reconstructed. The isodose curve chosen to prescribe the dose is 3 mm to 5 mm away from the skin surface. Three fractions of 8Gy are scheduled, 1 week apart, delivering a radiobiological equivalent of 48Gy of standard radiotherapy within 2 weeks. Our preliminary experience shows excellent early skin tolerance. The study is ongoing to assess efficacy and late effects.PACS number: 87.53.Jw
Interleukin-6 is an important in vivo inhibitor of intestinal epithelial cell death in mice
Authors: Jin Xiaoling , Zimmers Teresa A , Zhang Zongxiu , Pierce Robert H , Koniaris Leonidas G 
Published: December 2008

Background and aimsInterleukin-6 (IL-6) is a well-recognised mediator of liver disease and regeneration. However, the in vivo effects of IL-6 on enterocytes and the intestinal tract have not been elucidated. We sought to determine the in vivo effects of IL-6 on enterocytes.MethodsMurine models of increased or absent IL-6 were examined.ResultsSystemic, high-dose IL-6 administration to mice over 7–10 days resulted in intestinal hyperplasia with a ∼40% increase in small bowel mass and in intestinal villus height. No increase in crypt cell proliferation was noted. IL-6 administration was associated with induction of pSTAT3 in enterocytes along the lower and middle regions of villi but not in crypts. IL-6 administration was also associated with induction of anti-apoptotic proteins including pAKT, and FLIP along with decreased executor caspase activity and PARP cleavage. Pulse bromodeoxyuridine labelling demonstrated equivalent crypt cell proliferation rates but prolonged enterocyte lifespan and slowed enterocyte migration rates in IL-6 treated mice. Furthermore, IL-6 treated mice showed less intestinal injury and improved barrier function following ischaemia reperfusion of the small bowel. Conversely, Il6 null mice exhibited impaired recovery following massive enterectomy and increased apoptosis after 5-fluorouracil chemotherapy relative to wild-type controls.ConclusionsIL-6 inhibited both constitutive and induced enterocyte cell death in vivo. Loss of IL-6 in mice resulted in increased activation of pro-apoptotic and necrotic pathways in enterocytes after injury. Therapies that augment IL-6 or its signalling pathways may help manage intestinal disorders associated with increased apoptosis, necrosis and gut injury.
Distance education
Authors: Gal-Ezer Judith 
Published: December 2008

Opening Books for Academic Learning is a relative new trend, taking advantage of the potential of the Internet and computers.
In this issue I am honored to host a dear colleague, Dr. Yoav Yair, Head of the Center for Technology in Distance Education, at The Open University of Israel, who will describe a new initiative the university is engaged in, which might encourage other international academic institutions who haven't done so, to follow.
Evaluation of enoxaparin dosing requirements in infants and children
Authors: Belletrutti Mark , Bajzar Laszlo , Black Karina , Kuhle Stefan , Bauman Michelle , Massicotte M. Patricia , Bauman Mary 
Published: December 2008

SummaryIncreasing the starting dose of enoxaparin results in the early achievement of therapeutic anti-factor Xa levels in children receiving enoxaparin which is critical for effective therapy and the reduction of venipunctures. The aim of this study was: i) to determine the enoxaparin dose required to achieve therapeutic anti-factor Xa levels in infants and children, and ii) to establish whether increasing the starting dose of enoxaparin influenced the time required to reach the therapeutic range and the number of venipunctures required for dose-adjustment, and iii) the radiographic outcome of the thrombosis, where applicable. A retrospective chart review of children who received enoxaparin was carried out at the Stollery Children’s Hospital, Edmonton, Alberta, Canada. Patients treated with standard-dose enoxaparin (1.5 mg/kg for children ≤3 months of age, 1.0 mg/kg for children ≥3 months of age), were compared with children who received a higher initial starting dose of enoxaparin (1.7 mg/kg for children ≥3 months of age, 1.2 mg/kg for children ≥3 months of age). Infants <3 months required an enoxaparin dose of 1.83 mg/kg, and those who received an increased initial enoxaparin dose resulted in faster attainment of therapeutic anti-factor Xa levels requiring significantly fewer venipunctures. Similarly, infants ≥3–12 months, 1–5 years, and 6–18 years, require enoxaparin 1.48 mg/kg, 1.23 mg/kg and 1.13 mg/kg, respectively, in order to achieve a therapeutic anti-factor Xa level. In conclusion, increasing the starting dose of enoxaparin may result in more rapid attainment of therapeutic range with fewer venipunctures, dose adjustments, and without an increase in adverse events.
Immature platelets in patients with acute coronary syndromes
Authors: Hvas Anne-Mette , Kristensen Steen Dalby , Grove Erik Lerkevang 
Published: December 2008

SummaryPlatelets newly released from the bone marrow are RNA-containing and more haemostatically active than mature platelets. Immature platelets are reliably quantified by flow cytometry, and the immature platelet fraction (IPF) reflects platelet production and the rate of platelet turnover. It was the objective of this study to evaluate the presence of immature platelets in healthy subjects, patients with stable coronary artery disease (CAD) and patients with acute coronary syndromes. Flow cytometric determination of immature platelets was performed with an automated analyzer (Sysmex XE-2100) using RNA fluorescent dyes. IPF was determined in 420 individuals: 22 healthy subjects, 39 patients with stable CAD, 182 patients with unstable angina/ non-ST-segment elevation myocardial infarction (non-STEMI) and 177 patients with acute STEMI. The geometric mean [95% confidence interval] of IPF was 2.51 [2.04–3.10] in healthy subjects, 2.87 [2.45–3.36] in CAD patients, 2.93 [2.72–3.15] in the non-STEMI/unstable angina group and 3.71 [3.45–3.99] in patients with STEMI (ANOVA: p < 0.0001). This difference remained significant after adjusting for baseline characteristics (p = 0.0003). In active smokers, IPF was 18% higher than in non-smoking individuals (p = 0.007), and IPF was 16% higher in diabetics compared with non-diabetics (p = 0.060). In conclusion, the fraction of immature platelets is increased in acute coronary syndromes, especially in the acute phase of STEMI. Immature platelets with an increased haemostatic potential may contribute to coronary thrombus formation.
Drug-eluting balloon: Very short-term exposure and overlapping
Authors: Speck Ulrich , Kaufels Nicola , Mahnkopf Dirk , Kühler Michael , Böhm Michael , Scheller Bruno , Cremers Bodo 
Published: December 2008

SummaryPaclitaxel balloon coating has shown promising effects in inhibiting restenosis in initial clinical trials. The aim of the present study was to evaluate the influence of two critical features of drug-eluting balloon (DEB) application – inflation time and increased dose due to overlapping balloons. Fifty-six stainless steel stents were implanted in the left anterior descending and circumflex coronary arteries of 28 domestic pigs using a 1.2:1.0 overstretch ratio. Stents were mounted on conventional un-coated and paclitaxel-coated angioplasty balloon catheters. The animals were randomized to five different treatments with a range of short (10 seconds [s] inflation using 1 DEB) to extended (2x60 s inflation using 2 DEB) intima contact time. After 28 days, quantitative angiography and histomorphometry of the stented arteries was performed on a total of 23 pigs. Paclitaxel balloon coating led to a marked reduction of parameters characterizing in-stent stenosis: Late lumen loss was 1.37 ± 0.49 mm for uncoated balloons, 0.23 ± 0.42 mm for one coated balloon 60 s inflation time, 0.37 ± 0.28 mm for 10 s inflation time and 0.30 ± 0.19 mm for the vessel segment treated by two coated balloons with 60 s inflation each. Neointimal areas were 4.26 ± 1.18, 1.68 ± 0.23, 1.83 ± 0.40 and 1.67 ± 0.46 mm², respectively (p=0.001 versus control, p>0.05 between paclitaxel-treated groups). Despite the marked reduction of neointimal proliferation, endothelialization of stent struts was present in all samples. DEB were found to effectively reduce neointimal proliferation regardless of inflation time and dose within the tested range. No adverse reactions were seen as dose was increased to more than three times the clinically tested dose.
Clopidogrel versus prasugrel in rabbits
Authors: Watson Carol , Hua Ji , Schumacher William , Rehfuss Robert , Wong Pancras 
Published: December 2008

SummaryThe new P2Y12 antagonist prasugrel produces greater inhibition of ADP-induced platelet aggregation (IPA) and reduction of thrombotic events in patients versus approved doses of clopidogrel, but increases major bleeding. We examined whether IPA level or P2Y12 receptor occupancy (RO) could be optimized to better balance the efficacy and bleeding effects of these thienopyridines and reduce the response variability in rabbits. Rabbits were given three daily oral doses of clopidogrel (0.3–30 mg/ kg/d), prasugrel (0.03–10 mg/kg/d) or vehicle (n=6–40/group). Electrically-induced carotid artery thrombosis (AT, % thrombus weight reduction), cuticle bleeding time (BT, fold-increase over control), IPA to 20 μM ADP (% inhibition of peak light transmission) and RO (% inhibition of [33P]-2MeS-ADP binding to P2Y1-blocked platelets) were determined 2–3 hours after the last dose. ED50 (doses for half-maximal effect, mg/kg/d) of AT, BT, IPA and RO were 1.6, 6.7, 1.9 and 1.4 for clopidogrel vs. 1.2, 1.9, 0.5 and 0.2 for prasugrel. IPA of 30–40% for both compounds produced the optimal balances of efficacy (AT: 50–60%) and BT of about 2-fold with significant RO of 70–80%. IPA of 50–60% achieved higher efficacy (AT: 60–80%), but with increased BT of five- to six-fold and >90% RO. Box-plot suggests no significant difference in the IPA and RO response variability between both compounds. Clopidogrel was 1.3–7 times less potent than prasugrel in rabbits, depending upon which biomarker was studied. The ratio of efficacy:bleeding was most favorable at a moderate IPA of 30% to 40%. Both compounds had similar IPA and RO response variability.
Efficacy and safety of dabigatran etexilate for the prevention of venous thromboembolism following total hip or knee arthroplasty
Authors: Roskell Neil , Plumb Jonathan , Caprini Joseph , Eriksson Bengt , Wolowacz Sorrel 
Published: December 2008

SummaryDabigatran etexilate has been investigated in three phase III trials for the prevention of venous thromboembolism (VTE). Health technology assessment agencies increasingly require meta-analyses of all relevant evidence for an intervention, if appropriate. The objective of this study was to perform a meta-analysis of efficacy and safety data for the recommended dose of dabigatran etexilate, 220 mg once daily (od), for VTE prophylaxis after total knee arthroplasty (TKA) and total hip arthroplasty (THA), and discuss the appropriateness of combining the data. Risk ratios (RR) for VTE and bleed end-points were estimated using fixed and random effects meta-analysis. Analyses were performed combining RE-MODEL and RE-NOVATE, which compared dabigatran etexilate with enoxaparin 40 mg od after TKA and THA, respectively, and also including RE-MOBILIZE, which compared dabigatran etexilate with enoxaparin 30 mg twice daily after TKA. Tests for statistical heterogeneity were performed using the Chi-squared statistic. No significant differences were detected between dabigatran etexilate and enoxaparin in any of the end-points analysed, either in the two trial analysis (all p>0.15), or when all three trials were combined ( all p>0.30). RRs (random effects) for the composite end-point total VTE and all-cause mortality were 0.95 [95% confidence intervals 0.82 – 1.10] and 1.05 [0.87 – 1.26] in the two and three trial analyses, respectively. Meta-analysis of RE-MODEL and RE-NOVATE supported the conclusions of the individual trials that dabigatran etexilate is non-inferior to enoxaparin 40 mg od, with a similar safety profile. Meta-analysis of all three trials found no significant differences between treatments in any of the end-points analysed. Heterogeneity between the trials cannot be ruled out.
The technique of measuring thrombin generation with fluorescent substrates: 4. The H-transform, a mathematical procedure to obtain thrombin concentrations without external calibration
Authors: Hemker Pieter , Dieri Raed Al , Hemker Coen 
Published: December 2008

SummaryIn fluorogenic thrombin generation (TG) experiments, thrombin concentrations cannot be easily calculated from the rate of the fluorescent signal increase, because the calibration coefficient increases during the experiment, due to substrate consumption and quenching of the fluorescent signal by the product. Continuous, external calibration via an in a parallel sample therefore was hitherto required for an accurate calculation of the TG curve. A technique is presented that allows mathematical transformation of experimental fluorescence intensities into “ideal” data, i.e. in the data that would have been obtained if substrate consumption and quenching by the product would not play a role. The method applies to fluorescence intensities up to 90% of the maximal fluorescent signal corresponding to total substrate conversion and thereby covers the entire region of interest encountered in practice. The first derivative of the transformed signal can then be converted into thrombin concentrations via a conventional, fixed calibration factor. This calibration factor can be obtained from a separate experiment but also by measuring the amidolytic activity of the α2macroglobulin-thrombin complex present in the reaction mixture (“serum”) after thrombin generation is over. This method halves the amount of sample required per experiment.