bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of 2 Doses of Recombinant Human Thyrotropin for Thyroid Function Testing in Healthy and Suspected Hypothyroid Dogs
Authors: Boretti F.S. , Sieber‐Ruckstuhl N.S. , Wenger‐Riggenbach B. , Gerber B. , Lutz H. , Hofmann‐Lehmann R. , Reusch C.E.
Published: June 2009

Background:Various protocols using different doses of recombinant human thyrotropin (rhTSH) in TSH stimulation testing have been described. However, the influence of TSH dosage on thyroxine (T4) concentration has not yet been evaluated in suspected hypothyroid dogs.

Objective:To evaluate the effectiveness of 2 doses of rhTSH.

Animals:Fifteen dogs with clinical signs consistent with hypothyroidism and abnormal stimulation results with 75 μg rhTSH and 18 clinically healthy dogs.

Methods:All dogs were stimulated with 75 and 150 μg rhTSH IV in a 1st and 2nd stimulation test, respectively. Blood samples were taken before and 6 hours after rhTSH administration for determination of total T4 concentration.

Results:Using the higher dose led to a normal test interpretation in 9 of the 15 dogs, in which stimulation had been abnormal using the lower dose. Based on follow‐up information, hypothyroidism was excluded in 7 of these 9 dogs. In all 6 dogs with a blunted response to the higher dose, hypothyroidism could be confirmed. Healthy dogs showed significantly higher post‐TSH T4 concentrations with the higher compared with the lower dose. Post‐TSH T4 concentrations after TSH stimulation were not related to dogs' body weight in either healthy or diseased dogs.

Conclusions and Clinical Relevance:TSH dose significantly influenced test interpretation in suspected hypothyroid dogs. Differentiation between primary hypothyroidism and nonthyroidal disease was improved with 150 μg rhTSH. Because this effect was independent of the dogs' body weight, the higher dose is recommended in dogs that have concurrent disease or are receiving medication.
Evaluation of Predictors of the Development of Azotemia in Cats
Authors: Jepson R.E. , Brodbelt D. , Vallance C. , Syme H.M. , Elliott J.
Published: June 2009

Background:Chronic kidney disease (CKD) is a common condition in geriatric cats. Diagnosis is based on the development of persistent azotemia with inadequate urine concentrating ability. Biomarkers are sought for early identification.

Hypothesis:Clinical variables, urine concentrating ability, proteinuria, andN‐acetyl‐β‐d‐glucosaminidase (NAG) index will be predictive of cats at risk of developing azotemia within 12 months.

Animals:Client‐owned nonazotemic geriatric (≥9 years) cats.

Methods:Prospective longitudinal cohort study monitoring a population of healthy nonazotemic geriatric cats every 6 months until development of azotemia, death, or the study end point (September 30, 2007). Multivariable logistic regression analysis was used to assess baseline clinical, biochemical, and urinalysis variables, urine protein to creatinine ratio (UP/C), urine albumin to creatinine (UA/C) ratio, and urinary NAG index as predictors of development of azotemia.

Results:One hundred and eighteen cats were recruited with a median age of 13 years. Ninety‐five cats (80.5%) had been followed or reached the study end point by 12 months of which 30.5% (29/95) developed azotemia. Age, systolic blood pressure, plasma creatinine concentration, urine specific gravity, UP/C, UA/C, and NAG index were significantly associated with development of azotemia in the univariable analysis (P≤ .05). However, in the multivariable analysis, only plasma creatinine concentration with either UP/C (Model 1) or UA/C (Model 2) remained significant.

Conclusions and Clinical Importance:This study demonstrates a high incidence of azotemia in a population of previously healthy geriatric cats. Proteinuria at presentation was significantly associated with development of azotemia although causal association cannot be inferred. Evaluation of NAG index offered no additional benefit.
Analysis of 8 Sarcomeric Candidate Genes for Feline Hypertrophic Cardiomyopathy Mutations in Cats with Hypertrophic Cardiomyopathy
Authors: Meurs K.M. , Norgard M.M. , Kuan M. , Haggstrom J. , Kittleson M.
Published: June 2009

Background: Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats. Causative mutations have been identified in the Maine Coon (MC) and Ragdoll breed in the cardiac myosin binding protein C gene (MYBPC3). HCM is thought to be inherited in other breeds.

Hypothesis: That a causative mutation for HCM in the British Shorthair (BSH), Norwegian Forest (NWF), Siberian, Sphynx, or MC cats would be identified in the exonic and splice site regions of 1 of 8 genes associated with human familial HCM.

Animals: Three affected BSH, NWF, Siberians, Sphynx, 2 MC (without the known MC mutation), and 2 Domestic Shorthair cats (controls) were studied.

Methods: Prospective, observational study. Exonic and splice site regions of the genes encoding the proteins cardiac troponin I, troponin T, MYBPC3, cardiac essential myosin light chain, cardiac regulatory myosin light chain, α tropomyosin, actin, and β–myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected cats, the published DNA sequences, and control cats. Changes were considered to be causative for HCM if they involved a conserved amino acid and changed the amino acid to a different polarity, acid‐base status, or structure.

Results: A causative mutation for HCM was not identified, although several single nucleotide polymorphisms were detected.

Conclusions and Clinical Importance: Mutations within these cardiac genes do not appear to be the only cause of HCM in these breeds. Evaluation of additional cardiac genes is warranted to identify additional molecular causes of this feline cardiac disease.
Flow
Boiling Heat Transfer, Pressure Drop, and Flow Pattern for CO2
in a 3.5mm Horizontal Smooth
Tube
Authors: Park Chang
Yong , Hrnjak Pega
Published: June 2009

C O 2 flow boiling heat transfer coefficients and pressure drop in a 3.5mm horizontal smooth tube are presented. Also, flow patterns were visualized and studied at adiabatic conditions in a 3mm glass tube located immediately after a heat transfer section. Heat was applied by a secondary fluid through two brass half cylinders to the test section tubes. This research was performed at evaporation temperatures of −15°C and −30°C, mass fluxes of 200kg∕m2s and 400kg∕m2s, and heat flux from 5kW∕m2 to 15kW∕m2 for vapor qualities ranging from 0.1 to 0.8. The CO2 heat transfer coefficients indicated the nucleate boiling dominant heat transfer characteristics such as the strong dependence on heat fluxes at a mass flux of 200kg∕m2s. However, enhanced convective boiling contribution was observed at 400kg∕m2s. Surface conditions for two different tubes were investigated with a profilometer, atomic force microscope, and scanning electron microscope images, and their possible effects on heat transfer are discussed. Pressure drop, measured at adiabatic conditions, increased with the increase of mass flux and quality, and with the decrease of evaporation temperature. The measured heat transfer coefficients and pressure drop were compared with general correlations. Some of these correlations showed relatively good agreements with measured values. Visualized flow patterns were compared with two flow pattern maps and the comparison showed that the flow pattern maps need improvement in the transition regions from intermittent to annular flow.
Homotopy Analysis for Stagnation Slip Flow and Heat Transfer on a Moving Plate
Authors: Javed T. , Abbas Z. , Hayat T. , Asghar S.
Published: June 2009

The development of two-dimensional or axisymmetric stagnation flow of an incompressible viscous fluid over a moving plate with partial slip has been investigated. The effects of partial slip on the flow and heat transfer characteristics are considered. The equations of conservation of mass, momentum, and energy, which govern the flow and heat transfer, are solved analytically using homotopy analysis method. The convergence of the series solution is analyzed explicitly. Comparison of the present homotopy results is made with the existing numerical and asymptotic solution (Wang, 2006, “Stagnation Slip Flow and Heat Transfer on a Moving Plate,” Chem. Eng. Sci., 23, pp. 7668–7672) and an excellent agreement is achieved.
Direct Simulation Monte Carlo Solution of Subsonic Flow Through Micro/Nanoscale Channels
Authors: Roohi Ehsan , Darbandi Masoud , Mirjalili Vahid
Published: June 2009

We use a direct simulation Monte Carlo (DSMC) method to simulate gas heating/cooling and choked subsonic flows in micro/nanoscale channels subject to either constant wall temperature or constant/variable heat flux boundary conditions. We show the effects of applying various boundary conditions on the mass flow rate and the flow parameters. We also show that it is necessary to add a buffer zone at the end of the channel if we wish to simulate more realistic conditions at the channel outlet. We also discuss why applying equilibrium-based Maxwellian distribution on molecules coming from the channel outlet, where the flow is nonequilibrium, will not disturb the DSMC solution. The current velocity, pressure, and mass flow rate results are compared with different analytical solutions of the Navier–Stokes equations. Although there are good agreements between the DSMC results and the analytical solutions in low compressible flow, the analytical solutions yield incorrect velocity and mass flow rate values in short micro/nanochannel flows with high compressibility and/or choked flow conditions.
Objective index of image fidelity for JPEG2000 compressed body CT images
Authors: Kim Kil Joong , Lee Kyoung Ho , Kang Heung‐Sik , Kim So Yeon , Kim Young Hoon , Kim Bohyoung , Seo Jinwook , Mantiuk Rafal
Published: June 2009

Compression ratio (CR) has been the de facto standard index of compression level for medical images. The aim of the study is to evaluate the CR, peak signal‐to‐noise ratio (PSNR), and a perceptual quality metric (high‐dynamic range visual difference predictor HDR‐VDP) as objective indices of image fidelity for Joint Photographic Experts Group (JPEG) 2000 compressed body computed tomography (CT) images, from the viewpoint of visually lossless compression approach. A total of 250 body CT images obtained with five different scan protocols (5‐mm‐thick abdomen, 0.67‐mm‐thick abdomen, 5‐mm‐thick lung, 0.67‐mm‐thick lung, and 5‐mm‐thick low‐dose lung) were compressed to one of five CRs (reversible, 6:1, 8:1, 10:1, and 15:1). The PSNR and HDR‐VDP values were calculated for the 250 pairs of the original and compressed images. By alternately displaying an original and its compressed image on the same monitor, five radiologists independently determined if the pair was distinguishable or indistinguishable. The kappa statistic for the interobserver agreement among the five radiologists’ responses was 0.70. According to the radiologists' responses, the number of distinguishable image pairs tended to significantly differ among the five scan protocols at 6:1–10:1 compressions (Fisher‐Freeman‐Halton exact tests). Spearman's correlation coefficients between each of the CR, PSNR, and HDR‐VDP and the number of radiologists who responded as distinguishable were 0.72, −0.77, and 0.85, respectively. Using the radiologists' pooled responses as the reference standards, the areas under the receiver–operating–characteristic curves for the CR, PSNR, and HDR‐VDP were 0.87, 0.93, and 0.97, respectively, showing significant differences between the CR and PSNR , or HDR‐VDP , and between the PSNR and HDR‐VDP . In conclusion, the CR is less suitable than the PSNR or HDR‐VDP as an objective index of image fidelity for JPEG2000 compressed body CT images. The HDR‐VDP is more promising than the PSNR as such an index.
An adaptive incremental approach to constructing ensemble classifiers: Application in an information‐theoretic computer‐aided decision system for detection of masses in mammograms
Authors: Mazurowski Maciej A. , Zurada Jacek M. , Tourassi Georgia D.
Published: June 2009

Ensemble classifiers have been shown efficient in multiple applications. In this article, the authors explore the effectiveness of ensemble classifiers in a case‐based computer‐aided diagnosis system for detection of masses in mammograms. They evaluate two general ways of constructing subclassifiers by resampling of the available development dataset: Random division and random selection. Furthermore, they discuss the problem of selecting the ensemble size and propose two adaptive incremental techniques that automatically select the size for the problem at hand. All the techniques are evaluated with respect to a previously proposed information‐theoretic CAD system (IT‐CAD). The experimental results show that the examined ensemble techniques provide a statistically significant improvement in performance as compared to the original IT‐CAD system . Some of the techniques allow for a notable reduction in the total number of examples stored in the case base (to 1.3% of the original size), which, in turn, results in lower storage requirements and a shorter response time of the system. Among the methods examined in this article, the two proposed adaptive techniques are by far the most effective for this purpose. Furthermore, the authors provide some discussion and guidance for choosing the ensemble parameters.
Tolerances on MLC leaf position accuracy for IMRT delivery with a dynamic MLC
Authors: Rangel Alejandra , Dunscombe Peter
Published: June 2009

The objective determination of performance standards for radiation therapy equipment requires, ideally, establishing the quantitative relationship between performance deviations and clinical outcome or some acceptable surrogate. In this simulation study the authors analyzed the dosimetric impact of random (leaf by leaf) and systematic (entire leaf bank) errors in the position of the MLC leaves on seven clinical prostate and seven clinical head and neck IMRT plans delivered using a dynamic MLC. In‐house software was developed to incorporate normally distributed errors of up to ±2 mm in individual leaf position or systematic errors (±1 and ±0.5 mm in all leaves of both leaf banks or in one bank only) into the 14 plans, thus simulating treatment delivery using a suboptimally performing MLC. The dosimetric consequences of suboptimal MLC performance were quantified using the equivalent uniform doses (EUDs) of the clinical target volumes and important organs at risk (OARs). The deviation of the EUDs of the selected structures as the performance of the MLC deteriorated was used as the objective surrogate of clinical outcome. Random errors of 2 mm resulted in negligible changes for all structures of interest in both sites. In contrast, systematic errors can lead to potentially significant dosimetric changes that may compromise clinical outcome. If a 2% change in EUD of the target and 2 Gy for the OARs were adopted as acceptable levels of deviation in dose due to MLC effects alone, then systematic errors in leaf position will need to be limited to 0.3 mm. This study provides guidance, based on a dosimetric surrogate of clinical outcome, for the development of one component, leaf position accuracy of performance standards for multileaf collimators.
Methodology for generating a 3D computerized breast phantom from empirical data
Authors: Li Christina M. , Segars W. Paul , Tourassi Georgia D. , Boone John M. , Dobbins James T.
Published: June 2009

The initial process for creating a flexible three‐dimensional computer‐generated breast phantom based on empirical data is described. Dedicated breast computed‐tomography data were processed to suppress noise and scatter artifacts in the reconstructed image set. An automated algorithm was developed to classify the breast into its primary components. A preliminary phantom defined using subdivision surfaces was generated from the segmented data. To demonstrate potential applications of the phantom, simulated mammographic image data were acquired of the phantom using a simplistic compression model and an analytic projection algorithm directly on the surface model. The simulated image was generated using a model for a polyenergetic cone‐beam projection of the compressed phantom. The methods used to create the breast phantom generate resulting images that have a high level of tissue structure detail available and appear similar to actual mammograms. Fractal dimension measurements of simulated images of the phantom are comparatively similar to measurements from images of real human subjects. A realistic and geometrically defined breast phantom that can accurately simulate imaging data may have many applications in breast imaging research.
RSA calibration accuracy of a fluoroscopy‐based system using nonorthogonal images for measuring functional kinematics
Authors: Kedgley Angela E. , Jenkyn Thomas R.
Published: June 2009

When performing radiostereometric analysis (RSA) in a clinical setting it may be desirable to orient the two imaging devices nonorthogonally to obtain the best views of an anatomical structure. In this study, a calibration frame was constructed that allowed the relative angles of fiducial and control planes to be adjusted. Precision and accuracy were quantified across multiple trials and orientations. The 90° frame was always of equivalent or greater accuracy than a calibration frame with the fiducial and control planes aligned parallel to the image intensifiers. This study also showed that RSA may be performed with imaging devices at relative angles other than 90° without compromising accuracy. This allows researchers greater freedom in positioning equipment.
Mapping structural changes in breast tissue disease using x‐ray scattering
Authors: Sidhu Sabeena , Siu Karen K. W. , Falzon Gregory , Hart Stewart A. , Fox Jane G. , Lewis Robert A.
Published: June 2009

Spread of invasive carcinoma throughout breast tissue is believed to occur at supramolecular levels, beyond the range of standard histopathology identification. Small angle x‐ray scattering (SAXS) is capable of characterizing the structural properties of collagen and tissue found in the breast at the scale of tens to hundreds of nanometers. Fifty‐six patients who were treated with wide‐local excision or mastectomy had tissue biopsy samples analyzed at 2 cm intervals along two perpendicular axes over their excised mass, up to 6 cm away from the primary site of the tumor. Two SAXS parameters, the integrated amorphous scatter and the third order collagen axial spacing, showed significant differences between the center (0 cm) and distant tissues (2, 4, or 6 cm from the primary lesion). There was no evidence of directional trends (superior, inferior, or lateral sides of the nipple) of these two parameters over the breast. Mapping of these two variables over a two‐dimensional grid showed good matching with independent histopathology diagnosis. These results suggest that SAXS may be capable of identifying areas of invasion or directional spread of disease as well as providing more information at the supramolecular level for aiding tissue diagnosis.
The accuracy of the pencil beam convolution and anisotropic analytical algorithms in predicting the dose effects due to attenuation from immobilization devices and large air gaps
Authors: Gray A. , Oliver L. D. , Johnston P. N.
Published: June 2009

When a photon beam passes through the treatment couch or an immobilization device, it may traverse a large air gap (up to 15 cm or more) prior to entering the patient. Previous studies have investigated the ability of various treatment planning systems to calculate the dose immediately beyond small air gaps, typically less than 5 cm thick, such as those within the body. The aim of this study is to investigate the ability of the Eclipse anisotropic analytical algorithm (AAA) and pencil beam convolution (PBC) algorithm to calculate the dose beyond large air gaps. Depth dose data in water for a 6 MV photon beam, field size, and 100 cm SSD were measured beyond a range of air gaps (1–15 cm). The thickness of the water equivalent material positioned before the air gap ranged from 0.2 to 4 cm. Dose was calculated with the Eclipse PBC algorithm and AAA. The scattered and primary dose components were calculated from the measurements. The measured results indicate that as the air gap increases (from 1 to 15 cm) the dose reduces at the water surface and that beyond an air gap a secondary buildup region is required to re‐establish electronic equilibrium. The dose beyond the air gap is also reduced at depths beyond the secondary buildup region. The PBC algorithm did not predict any reduction in dose beyond the air gap. AAA predicted the secondary buildup region but did not predict the reduction in dose at depths beyond it. The reduction in dose beyond the secondary buildup region was shown to be particularly relevant for air gaps of 5 cm or more when there was a 2 cm of water equivalent material positioned before the air gap. For these cases, where electronic equilibrium is established in the material positioned before the air gap, both algorithms were found to overestimate the dose by 2.0%–5.5%. It was concluded that the dose to depths of up to 15 cm beyond a large air gap is reduced due to a decrease in scattered radiation, produced in the material positioned before the air gap, reaching the point of interest. This effect is not well modeled by the Eclipse AAA and PBC algorithm and may result in dose calculation errors greater than 2.5%. Due to the contribution of other uncertainties in the radiation therapy treatment planning and delivery process, dose calculation errors of this magnitude are not consistent with the recommendation of the International Commission on Radiation Units and Measurements that the absorbed dose to the target volume be delivered with an uncertainty of less than ±5%.
Differential dose volume histograms of Gamma Knife in the presence of inhomogeneities using MRI–polymer gel dosimetry and MC simulation
Authors: Allahverdi Pourfallah Tayyeb , Allahverdi Mahmoud , Riahi Alam Nader , Ay Mohammad‐Reza , Zahmatkesh Mohammad‐Hasan
Published: June 2009

Polymer gel dosimeters offer a practical solution to 3D dose verification for conventional radiotherapy as well as intensity‐modulated and stereotactic radiotherapy. In this study, EGSnrc calculated and PAGAT polymer gel dosimeter measured dose volume histograms (DVHs) for single‐shot irradiations of the Gamma Knife (GK) unit were used to investigate the effects of the presence of inhomogeneities on 3D dose distribution. The head phantom was a custom‐built 16 cm diameter Plexiglas sphere. Inside the phantom, there is a cubic cutout for inserting the gel vials and another cutout for inserting the inhomogeneities. Following irradiation with the GK unit, the polymer gel phantoms were scanned with a 1.5 T MRI scanner. Comparing the results of measurement in homogeneous and heterogeneous phantoms revealed that inserting inhomogeneities inside the homogeneous phantom did not cause considerable disturbances on dose distribution in irradiation with 8 mm collimator within low isodose levels , which is essential for the dose sparing of sensitive structures. The results of simulation for homogeneous and inhomogeneous phantoms in irradiation with 18 mm collimator of the GK unit showed 23.24% difference in DVH within 90%–100% relative isodose level and also revealed that a significant part of the target (28.56%) received relative doses higher than the maximum dose, which exceeds the acceptance criterion (5%). Based on these results it is concluded that the presence of inhomogeneities inside the phantom can cause considerable errors in dose calculation within high isodose levels with respect to LGP prediction which assumes that the target is a homogeneous material. Moreover, it is demonstrated that the applied MC code is an accurate and stand‐alone tool for 3D evaluation of dose distribution in irradiation with the GK unit, which can provide important, 3D plan evaluation criteria used in clinical practice.
Temporal and dose dependence of T2 and ADC at 9.4 T in a mouse model following single fraction radiation therapy
Authors: Larocque Matthew P. , Syme Alasdair , Yahya Atiyah , Wachowicz Keith , Allalunis‐Turner Joan , Fallone B. Gino
Published: June 2009

The purpose of this study is to use magnetic resonance imaging to monitor the response of human glioma tumor xenografts to single fraction radiation therapy. Mice were divided into four treatment groups ( per group) that received 50, 200, 400, or 800 cGy of 200 kVp x rays. A fifth group received no radiation dose and served as the control. Quantitative maps of the treated tumor tissue were produced of water apparent diffusion coefficient (ADC) and transverse relaxation time (T2). Mice were imaged before and at multiple time points after treatment. There was a statistically significant difference in tumor growth relative to that of the control for all treatment groups. Only the highest dose group showed T2 values that were significantly different at all measured time points after treatment. In this group, there was an 8.3% increase in T2 relative to controls 2 days after treatment, but when measured 14 days after treatment, mean tumor T2 had dropped to 10.1% below the initial value. ADC showed statistically significant differences from the control at all dose points. A radiation dose dependence was observed. In the highest dose group, the fractional increases in ADC were higher than those observed for T2. ADC was sensitive to radiation‐induced changes in lower dose groups that did not have significant T2 change. At all doses, elevation of mean tumor ADC preceded deviations in tumor growth from the control. These observations support the potential application of ADC as a time and dose sensitive marker of tumor response to radiation therapy.
Diffraction and coherence in breast ultrasound tomography: A study with a toroidal array
Authors: Simonetti F. , Huang L. , Duric N. , Littrup P.
Published: June 2009

Ultrasound is commonly used as an adjunct to mammography for diagnostic evaluation of suspicions arising from breast cancer screening. As an alternative to conventional sonography that uses hand‐held transducers, toroidal array probes that encircle the breast immersed in a water bath have been investigated for ultrasound tomography. In this paper, two sets of experiments performed with a prototype ultrasound scanner on a phantom and a human breast in vivo are used to investigate the effects of diffraction and coherence in ultrasound tomography. Reconstructions obtained with transmission diffraction tomography (TDT) are compared with conventional reflection imaging and computerized ultrasound tomography showing a substantial improvement. The in vivo tests demonstrate that TDT can image the complex boundary of a cancer mass and suggest that it can reveal the anatomy of milk ducts and Cooper's ligaments.
Incorporating uncertainties in respiratory motion into 4D treatment plan optimization
Authors: Heath Emily , Unkelbach Jan , Oelfke Uwe
Published: June 2009

The purpose of this work is to investigate robust 4D optimization techniques which account for respiratory motion uncertainties. Two robust optimization techniques were applied to generate 4D optimized lung treatment plans. The probabilistic optimization approach minimizes the dose variance in the target volume while the worst case optimization minimizes a weighted combination of the nominal and worst case dose distributions which occur in the presence of respiratory motion variation. The two 4D optimization approaches were compared with a margin‐based midventilation planning approach in five lung patients. Respiratory motion amplitude and baseline variations were quantified from tidal volume measurements during planning 4D CT acquisition. A similar target coverage was obtained for all three approaches, although the 4D optimization methods tended to be better at sparing the organs at risk. Both robust planning methods are suited for automatic determination of treatment plans which ensure target dose conformality under respiratory motion variations, while minimizing the dose burden of healthy lung tissue.
An approach to multiobjective optimization of rotational therapy
Authors: Pardo‐Montero Juan , Fenwick John D.
Published: June 2009

Multiobjective optimization is used in radiotherapy, especially IMRT, to generate treatment plans which meet different objectives to varying extents. Trade‐off surfaces can be constructed representing the gains and losses of different objectives when switching from one plan to another, and the planner can interactively explore different treatment possibilities without the need for reoptimization. In this work a method for the multiobjective optimization of rotational therapy is introduced. The proposed method is applied slice per slice and uses the geometry of the slice directly to construct several arcs, each conformally irradiating the tumor and blocking a number of different organs at risk present in the treatment. The blocked arc dose distributions so obtained are quite inhomogeneous in the target. An algorithm, based on the iterative reconstruction of images from projections, has been developed to compensate for this inhomogeneity, leading to compensated blocked arcs which deliver more uniform target doses but still block critical structures. Different treatments can be obtained as linear combinations of these arcs, each involving different trade‐offs among the objectives involved. The compensatory algorithm substantially improves the target dose uniformity of blocked arcs at the cost of slightly increasing the dose to the rest of the body, allowing delivery of good uniform dose distributions to the target without significantly irradiating the blocked organ(s). Trade‐off surfaces are presented for slices containing a target and one or two critical structures. The method is directly implementable using axial or helical tomotherapy. Implementation for conventional linear accelerators will be more difficult because the number of arcs needed to deliver such treatments can be large, an issue to be explored in future work.
Field size dependence of the output factor in passively scattered proton therapy: Influence of range, modulation, air gap, and machine settings
Authors: Daartz J. , Engelsman M. , Paganetti Harald , Bussière M. R.
Published: June 2009

At the Francis H. Burr Proton Therapy Center field specific output factors (i.e., dose per monitor unit) for patient treatments were modeled for all beamlines (two gantries, fixed stereotactic, and fixed eye beamline). The authors evaluated the accuracy of dose calculation and output model for small fields. Measurements in a water phantom were performed in three of our beamlines quantifying the dependency of the output factor on the field size for a variety of proton ranges. The influence of snout size, air gap, modulation, and second scatterer was investigated. The impact of field size on output depends strongly on the depth of interest. The air gap has a notable influence on small field outputs. A field size specific correction factor to the output is necessary if the latter was modeled or measured without the custom hardware in place. The output was shown to be field size dependent even for large fields, indicating an effect beyond charged particle disequilibrium caused by lateral scatter.
An analytical approach to estimating the first order x‐ray scatter in heterogeneous medium
Authors: Yao Weiguang , Leszczynski Konrad W.
Published: June 2009

X‐ray scatter estimation in heterogeneous medium is a challenge in improving the quality of diagnostic projection images and volumetric image reconstruction. For Compton scatter, the statistical behavior of the first order scatter can be accurately described by using the Klein‐Nishina expression for Compton scattering cross section provided that the exact information of the medium including the geometry and the attenuation, which in fact is unknown, is known. The authors present an approach to approximately separate the unknowns from the Klein‐Nishina formula and express the unknown part by the primary x‐ray intensity at the detector. The approximation is fitted to the exact solution of the Klein‐Nishina formulas by introducing one parameter, whose value is shown to be not sensitive to the linear attenuation coefficient and thickness of the scatterer. The performance of the approach is evaluated by comparing the result with those from the Klein‐Nishina formula and Monte Carlo simulations. The approximation is close to the exact solution and the Monte Carlo simulation result for parallel and cone beam imaging systems with various field sizes, air gaps, and mono‐ and polyenergy of primary photons and for nonhomogeneous scatterer with various geometries of slabs and cylinders. For a wide range of x‐ray energy including those often used in kilo‐ and megavoltage cone beam computed tomographies, the first order scatter fluence at the detector is mainly from Compton scatter. Thus, the approximate relation between the first order scatter and primary fluences at the detector is useful for scatter estimation in physical phantom projections.
Monte Carlo modeling of small photon fields: Quantifying the impact of focal spot size on source occlusion and output factors, and exploring miniphantom design for small‐field measurements
Authors: Scott Alison J. D. , Nahum Alan E. , Fenwick John D.
Published: June 2009

The accuracy with which Monte Carlo models of photon beams generated by linear accelerators (linacs) can describe small‐field dose distributions depends on the modeled width of the electron beam profile incident on the linac target. It is known that the electron focal spot width affects penumbra and cross‐field profiles; here, the authors explore the extent to which source occlusion reduces linac output for smaller fields and larger spot sizes. A BEAMnrc Monte Carlo linac model has been used to investigate the variation in penumbra widths and small‐field output factors with electron spot size. A formalism is developed separating head scatter factors into source occlusion and flattening filter factors. Differences between head scatter factors defined in terms of in‐air energy fluence, collision kerma, and terma are explored using Monte Carlo calculations. Estimates of changes in kerma‐based source occlusion and flattening filter factors with field size and focal spot width are obtained by calculating doses deposited in a narrow 2 mm wide virtual “milliphantom” geometry. The impact of focal spot size on phantom scatter is also explored. Modeled electron spot sizes of 0.4–0.7 mm FWHM generate acceptable matches to measured penumbra widths. However the 0.5 cm field output factor is quite sensitive to electron spot width, the measured output only being matched by calculations for a 0.7 mm spot width. Because the spectra of the unscattered primary and head‐scattered photon energy fluences differ, miniphantom‐based collision kerma measurements do not scale precisely with total in‐air energy fluence but with . For most field sizes, on‐axis collision kerma is independent of the focal spot size; but for a 0.5 cm field size and 1.0 mm spot width, it is reduced by around 7% mostly due to source occlusion. The phantom scatter factor of the 0.5 cm field also shows some spot size dependence, decreasing by 6% (relative) as spot size is increased from 0.1 to 1.0 mm. The dependence of small‐field source occlusion and output factors on the focal spot size makes this a significant factor in Monte Carlo modeling of small fields. Changes in penumbra width with spot size are not sufficiently large to accurately pinpoint spot widths. Consequently, while Monte Carlo models based exclusively on large‐field data can quite accurately predict small‐field profiles and PDDs, in the absence of experimental methods of determining incident electron beam profiles it will remain necessary to measure small‐field output factors, fine‐tuning modeled spot sizes to ensure good matching between the Monte Carlo and the measured output factors.
Advanced Imaging in Biology and Medicine: Technology, Software Environments, Applications
Authors: Khan Rao F. H.
Published: June 2009

Advanced Imaging in Biology and Medicine: Technology, Software Environments, Applications Sensen Christoph W. and Hallgrímsson Benedikt Springer‐Verlag, Berlin, Heidelberg, Germany, 2009. $249.00. ISBN: 9783540689928, 445 pp. (hardcover).
An ER-Mitochondria Tethering Complex Revealed by a Synthetic Biology Screen
Authors: Kornmann Benoît , Currie Erin , Collins Sean R. , Schuldiner Maya , Nunnari Jodi , Weissman Jonathan S. , Walter Peter
Published: June 2009

Making Connections

Endoplasmic reticulum (ER)–mitochondria connections have been implicated in many physiological processes, including calcium homeostasis, signaling, membrane biogenesis, and apoptosis.

Kornmann
et al.

(p.
477
, published online 25 June; see the Perspective by

Wiedemann
et al.

) looked for a proteinaceous link between the ER and mitochondria and, using combinations of synthetic biology and classical yeast genetics, found a protein complex that tethers the two organelles. A large-scale genetic interaction map suggests that these ER-mitochondria connections are important for interorganellar phospholipid exchange.
Catalytic effect of alloxazinium and isoalloxazinium salts on oxidation of sulfides with hydrogen peroxide in micellar media
Authors: Cibulka Radek , Baxová Lenka , Dvořáková Hana , Hampl František , Ménová Petra , Mojr Viktor , Plancq Baptiste , Sayin Serkan
Published: June 2009

Three novel amphiphilic alloxazinium salts were prepared: 3-dodecyl-5-ethyl-7,8,10-trimethylisoalloxazinium perchlorate (1c), 1-dodecyl-5-ethyl-3-methylalloxazinium perchlorate (2b), and 3-dodecyl-5-ethyl-1-methylalloxazinium perchlorate (2c). Their catalytic activity in thioanisole (3) oxidation with hydrogen peroxide was investigated in micelles of sodium dodecylsulfate (SDS), hexadecyltrimethylammonium nitrate (CTANO3) and Brij 35. Reaction rates were strongly dependent on the catalyst structure, on the type of micelles, and on pH value. Alloxazinium salts 2 were more effective catalysts than isoalloxazinium salts 1. Due to the contribution of micellar catalysis, the vcat/v0 ratio of the catalyzed and non-catalyzed reaction rates was almost 80 with salt 2b solubilized in CTANO3 micelles. Nevertheless, the highest acceleration was observed with non-amphiphilic 5-ethyl-1,3-dimethylalloxazinium perchlorate (2a) in CTANO3 micelles (vcat/v0 = 134). In this case, salt 2a presumably acts as a phase-transfer catalyst bringing hydrogen peroxide from the aqueous phase into the micelle interior. Synthetic applicability of the investigated catalytic systems was verified on semi-preparative scale.
Bio- and air-tolerant carbon–carbon bond formations via organometallic ruthenium catalysis
Authors: Adriaenssens Louis , Severa Lukáš , Vávra Jan , Šálová Tereza , Hývl Jakub , Čížková Martina , Pohl Radek , Šaman David , Teplý Filip
Published: June 2009

Selected [2+2+2] cycloadditions, alkene–alkyne coupling and fusion of enyne with diazo compound, all triggered by an artificial organometallic ruthenium catalyst are demonstrated to proceed under ambient aerobic aqueous conditions in presence of bodily fluids or cell lysate. To the best of our knowledge, these are the first examples of bio- and air-tolerant C–C bond formation catalyzed by an artificial organometallic compound.
Clinical audit in the laboratory
Authors: Erasmus R T , Zemlin A E
Published: June 2009

Audits are part of the continuous quality improvement process and one of the key elements of clinical governance. Laboratory-based clinical audits are concerned primarily with the everyday aspects of laboratory services and are a means of providing feedback to the users of the laboratory and its staff. They involve measuring the performance of laboratory services against established standards. These standards have ideally been established using the principles of evidence-based medicine. If necessary, changes are implemented and then a re-audit is performed after a certain time period to ensure that the changes have been implemented and maintained. Areas of audit in the laboratory include the preanalytical, analytical and postanalytical phases. This review article examines the basis of clinical audits in the laboratory and then proceeds to describe in detail how a laboratory-based clinical audit should be performed and monitored, with special reference to the chemical pathology laboratory.
Genomic profile of a secretory breast cancer with anETV6–NTRK3duplication
Authors: Lambros M B K , Tan D S P , Jones R L , Vatcheva R , Savage K , Tamber N , Fenwick K , Mackay A , Ashworth A , Reis-Filho J S
Published: June 2009

Background:

Secretory breast cancer (SBC) is a rare entity characterised by indolent clinical behaviour, distinctive histological features and the presence of a recurrent chromosomal translocation t(12;15)(p13;q25), leading to the formation of theETV6–NTRK3fusion gene.

Aim:

To describe the molecular genetic features of a case of SBC which harbours a duplication of the t(12;15) translocation.

Methods:

Tiling path array comparative genomic hybridisation (aCGH) analysis and fluorescence in situ hybridisation (FISH) using in-house-generated probes forETV6,NTRK3and the fusion genes, centromeric probes for chromosomes 12 and 15, and a commercially available split-apartETV6/NTRK3probe.

Results:

FISH revealed the presence of a duplication of the translocation t(12;15), which resulted from the gain of one copy of the derivative chromosome der(15)t(12;15), retention of one normal copy of bothETV6andNTRK3genes and deletion of the derivative chromosome der(12)t(12;15). Consistent with FISH findings, aCGH revealed copy number gains ofETV6andNTRK3and deletions encompassing the regions centromeric toETV6and telomeric toNTRK3. Additional regions of copy number changes included gains of 10q21, 10q26.3, 12p13.3–p13.31 15q11–q25.3 and 16pq and losses of 6q24.1–q27, 12p13.2–q12 and 15q25.3–q26.3.

Conclusions:

To the best of our knowledge, this is the first time a carcinoma has been shown to harbour a duplication of theETV6–NTRK3translocation. The presence of an additional copy of the derivative chromosome der(15)t(12;15) coupled with deletion of the other derivative der(12)t(12;15) in the modal population of cancer cells suggests that this was either an early phenomenon or conferred additional growth advantage on neoplastic cells.
Triple negative breast cancer: a study from the point of view of basal CK5/6 and HER-1
Authors: Pintens S , Neven P , Drijkoningen M , Van Belle V , Moerman P , Christiaens M-R , Smeets A , Wildiers H , Bempt I Vanden
Published: June 2009

Aim:

Basal-like breast tumours, as defined by microarrays, carry a poor prognosis and therapeutic options are limited to date. Often, these tumours are defined as oestrogen receptor (ER) negative/progesterone receptor (PR) negative/human epidermal growth factor receptor 2 (HER-2) negative (triple negative) by immunohistochemistry (IHC), but a more complete definition should include expression of basal cytokeratins (CK5/6, CK14 or CK17) and/or human epidermal growth factor receptor 1 (HER-1). The aim of this study was to investigate to what extent CK5/6 and HER-1 characterise the group of triple negative breast cancers.

Methods:

Expression of CK5/6 and HER-1 was studied by IHC in 25 triple negative breast carcinomas and 32 grade-matched, non-triple-negative controls. All 57 cases were further subjected to fluorescence in situ hybridisation to investigateHER-1gene copy number.

Results:

CK5/6 and HER-1 expression was most frequent in triple negative tumours: 22 out of 25 cases (88.0%) expressed at least one of these markers (60.0% CK5/6 positive and 52.0% HER-1 positive). In the control group, CK5/6 and HER-1 expression was found in ER-negative but not in ER-positive tumours (ER negative/PR negative/HER-2 positive tumours: 20.0% CK5/6 positive and 46.7% HER-1 positive).HER-1gene amplification was found in five cases only: four triple negative (16.0%) and one ER-negative control (ER negative/PR negative/HER-2 positive, 6.7%). Of interest, all fiveHER-1amplified cases showed a remarkably homogeneous HER-1 expression pattern.

Conclusion:

Expression of CK5/6 and HER-1 is frequent in ER-negative breast cancers, in triple negative and in non-triple negative tumours. In a minority of cases, HER-1 overexpression may be caused byHER-1gene amplification. Further studies are needed to investigate whether such cases might benefit from anti-HER-1 therapy
Vulvar plasmablastic lymphoma in a HIV-positive child: a novel extraoral localisation
Authors: Chabay P , De Matteo E , Lorenzetti M , Gutierrez M , Narbaitz M , Aversa L , Preciado M V
Published: June 2009

Plasmablastic lymphoma (PBL) has been characterised by the World Health Organization as a new entity. This report describes an unusual case of PBL in a 3-year-old HIV-infected patient showing a cutaneous vulvar lesion with 9 months of evolution and prolapsed vulvovaginal mucosa. Histopathological examination of a biopsy sample showed diffuse submucosal infiltration by large cells with a cohesive growth pattern, and round and vesicular nuclei with fine chromatin centrally or eccentrically placed with one or more prominent nucleoli. Immunohistochemical staining in neoplastic cells was positive for multiple melanoma oncogene (MUM1), CD138, CD45 and epithelial membrane antigen (EMA). The diagnosis was PBL, stage III. Epstein–Barr virus (EBV) expression was positive by EBV encoded RNAs in situ hybridisation. This is believed to be the third case of paediatric HIV-associated PBL reported in the literature, and the first with vulvar localisation, which is a new anatomical location for this entity.
Composite phaeochromocytoma with malignant peripheral nerve sheath tumour and rhabdomyosarcomatous differentiation in a patient without von Recklinghausen disease
Authors: Gupta R , Sharma A , Arora R , Vijayaraghavan M
Published: June 2009

The coexistence of adrenal phaeochromocytoma with non-chromaffin tumours is a rare fascinating occurrence. This category of tumours is subdivided into “composite” and “mixed”. The coexistence of adrenal phaeochromocytoma with a malignant Triton tumour does not appear to have been described in the available literature so far. A unique case of composite phaeochromocytoma in a 26-year-old male patient, where the non-chromaffin component was a malignant Triton tumour composed of peripheral nerve sheath tumour and skeletal muscle differentiation, is reported. This admixture was confirmed with immunohistochemical pattern of expression. This is the first case of such a phenomenon in a composite phaeochromocytoma. The present case further widens the histomorphological range of composite phaeochromocytoma of the adrenal gland, which the histopathologist should be aware of. Since the prognosis of composite phaeochromocytoma with malignant nerve sheath tumour would be determined by the nerve sheath component, recognition of this tumour is imperative.