Search

Background The large fractional doses, steep dose gradients, and small targets found in intracranial radiosurgery require extremely low beam delivery uncertainty. In the case of Gamma Knife radiosurgery (GKRS), this includes minimizing patient positioning system (PPS) positioning uncertainty. Existing QA techniques are recipe based, and feature point in time pass/fail tolerances. However, modern treatment machines, including the Gamma Knife Perfexion/Icon systems, record extensive internal data in treatment logs. These data can be analyzed through statistical process control (SPC) methods which are designed to detect changes in process behavior. The purpose of this study was to characterize the long-term (8+ year) performance of a Perfexion/Icon unit and use SPC methods to determine if performance changes could be detected at levels lower than existing QA and internal manufacturer performance tolerances. Methods In-house software was developed to parse Perfexion/Icon log-files and store relevant information on shot delivery in a relational database. A last-in, first-out (LIFO) queuing algorithm was created to heuristically match messages associated with a given delivered shot. Filtering criteria were developed to filter QA and uncompleted shots. The resulting matched shots were extracted. Achieved versus planned PPS position was determined for each PPS motor as well as for the vector magnitude difference in PPS position. Exponentially weighted moving average (EWMA) control charts were plotted to determine when process behavior changed over time. Results 53833 shots were delivered over an 8+ year span in the study. The mean vector magnitude PPS difference was 32.7 µm, with 97.5% of all shots within 70.1 µm. Several changes in PPS positioning behavior were observed over time, corresponding with control system faults on several occasions requiring PPS recalibration. EWMA control charts clearly demonstrate that these faults could be identified and possibly predicted as many as 3 years before there were faults beyond control system tolerance. Conclusion The PPS of Gamma Knife Perfexion/Icon systems has extremely low positioning uncertainties. EWMA control chart method can be utilized to track PPS performance over time and can potentially detect changes in performance that may indicate a component requiring maintenance. This would allow planned service visits to mitigate problems and prevent unplanned downtime.

In the last decade, the concept of ‘global value chain’ (GVC) has become popular to describe the way firms fragment production into different stages that are located in different economies. However, recent evidence indicates that there are lower levels of fragmentation of production. Some authors also suggest that supply chains are regional rather than global. We offer a comprehensive review of the evidence based on the 2018 update of the OECD trade in value added database. The ‘made in the world’ narrative is correct when describing the rise of GVCs in the 2000s. But globalization reached a peak in 2012, and since then supply chains are becoming more domestic rather than more regional.

Introduction Monte Carlo (MC) simulations are a powerful tool for improving image quality in X-ray based imaging modalities. An accurate X-ray source model is essential to MC modeling for CBCT but can be difficult to implement on a GPU while maintaining efficiency and memory limitations. A statistical analysis of the photon distribution from a MC X-ray tube simulation is conducted in hopes of building a compact source model. Materials & methods MC simulations of an X-ray tube were carried out using BEAMnrc. The resulting photons were sorted into four categories: primary, scatter, off-focal radiation (OFR), and both (scatter and OFR). A statistical analysis of the photon components (energy, position, direction) was completed. A novel method for a compact (memory efficient) representation of the PHSP data was implemented and tested using different statistical based linear transformations (PCA, ZCA, ICA), as well as a geometrical transformation. Results The statistical analysis showed all photon groupings had strong correlations between position and direction, with the largest correlation in the primary data. The novel method was successful in compactly representing the primary (error Discussion & conclusion Statistical linear transforms provide a method of reducing the memory required to accurately simulate an X-ray source in a GPU MC system. If all photon types are required, the proposed method reduces the memory requirements by 3.8 times. When only primary and scatter data is needed, the memory requirement is reduced from gigabytes to kilobytes.

Stereotactic radiosurgery (SRS) involves the focal delivery of large, cytotoxic doses of radiation to small targets within the brain, often located in close proximity to radiosensitive normal tissue structures and requiring very low procedural uncertainties to perform safely. Historically, neurosurgeons considered SRS as a one-time, single session procedure. However therapeutic advances and a better understanding of the clinical response to SRS have caused a renewal of interest in a variety of re-irradiation scenarios; including re-irradiation of the same target after prior SRS, SRS treatments after prior broad-field radiation, hypofractionated treatments, and volume-staged treatments. Re-irradiation may in some cases require even greater effort towards minimizing treatment uncertainties as compared to one-time-only treatments. Gamma Knife radiosurgery (GKRS) has evolved over time in ways that directly supports many re-irradiation scenarios while helping to minimize overall procedural uncertainty.

Purpose Leksell Gamma Knife® is a stereotactic radiosurgery system that allows fine-grained control of the delivered dose distribution. We describe a new inverse planning approach that both resolves shortcomings of earlier approaches and unlocks new capabilities. Methods We fix the isocenter positions and perform sector-duration optimization using linear programming, and study the effect of beam-on time penalization on the trade-off between beam-on time and plan quality. We also describe two techniques that reduce the problem size and thus further reduce the solution time: dualization and representative subsampling. Results The beam-on time penalization reduces the beam-on time by a factor 2-3 compared with the naive alternative. Dualization and representative subsampling each leads to optimization time-savings by a factor 5-20. Overall, we find in a comparison with 75 clinical plans that we can always find plans with similar coverage and better selectivity and beam-on time. In 44 of these, we can even find a plan that also has better gradient index. On a standard GammaPlan workstation, the optimization times ranged from 2.3 to 26 s with a median time of 5.7 s. Conclusion We present a combination of techniques that enables sector-duration optimization in a clinically feasible time frame.

Simple Summary This study proposes a novel strategy in brain cancer management. Stereotactic radiosurgery delivered by the Gamma Knife was combined with hyperthermia. For the radiobiological modelling of this synergistic treatment modality, we used the linear-quadratic model with temperature-dependent parameters to assess the potential enhancement of the therapeutic outcome. The results indicate that focused intracranial heating can be used to boost the dose to the target. Alternatively, one can conclude that for the same therapeutic effect, hyperthermia can help to minimize the dose undesirably delivered to healthy tissues. This study is also the first to advocate a combination of stereotactic radiosurgery with focused heating and motivates the future development of hyperthermia systems for brain cancer treatment. Abstract Combining radiotherapy (RT) with hyperthermia (HT) has been proven effective in the treatment of a wide range of tumours, but the combination of externally delivered, focused heat and stereotactic radiosurgery has never been investigated. We explore the potential of such treatment enhancement via radiobiological modelling, specifically via the linear-quadratic (LQ) model adapted to thermoradiotherapy through modulating the radiosensitivity of temperature-dependent parameters. We extend this well-established model by incorporating oxygenation effects. To illustrate the methodology, we present a clinically relevant application in pediatric oncology, which is novel in two ways. First, it deals with medulloblastoma, the most common malignant brain tumour in children, a type of brain tumour not previously reported in the literature of thermoradiotherapy studies. Second, it makes use of the Gamma Knife for the radiotherapy part, thereby being the first of its kind in this context. Quantitative metrics like the biologically effective dose (BED) and the tumour control probability (TCP) are used to assess the efficacy of the combined plan.

BACKGROUND On a new dedicated radiosurgery unit enabling frameless treatments, a cone-beam computed tomography (CBCT) can be used for stereotactic definition. Since magnetic resonance imaging (MRI) is used to delineate target, reproducible MRI-to-CBCT coregistration is vital for accurate target localization. OBJECTIVE To evaluate reproducibility of image coregistration in patient images. METHODS Three types of coregistration (source-to-target) were analyzed: (1) MRI-to-CT; (2) MRI-to-CBCT; and (3) CT-to-CBCT. For each patient (n = 15), each coregistration type was independently performed 5 to 30 times (total: 465 coregistrations). Each coregistration yielded a transformation matrix, which was subsequently applied to transform every point in the source image to stereotactic coordinates. Two metrics were measured: (1) target registration error (TRE): mean distance between the registered position of each target point and the average registration position of that point; (2) compound registration error (CRE): mean spatial difference between stereotactic coordinates using (A) MRI-to-CT-to-CBCT and (B) MRI-to-CBCT. RESULTS The median (range) of TRE was 0.11 mm (0.06-0.22 mm), 0.17 mm (0.10-0.36 mm), and 0.12 mm (0.08-0.21 mm) for MRI-to-CT, MRI-to-CBCT, and CT-to-CBCT, respectively. The TRE for MRI-to-CBCT was statistically higher than the other 2 methods (P

Purpose We present a new method for knowledge-based isocenter selection for treatment planning in radiosurgery. Our objective is to develop a prediction model that can learn from past manually designed treatment plans. We leverage recent advances in deep learning to predict isocenter locations in treatment plans in order to provide a decision support tool. Methods The proposed method adapts a geometric approach using orthogonal moment expansions as a feature vector for describing the shape of the tumor. Our approach accounts primarily for tumor shape and OAR proximity, the two factors that are known to greatly affect the isocenter placement. We solve the prediction problem by training a residual neural network with skip connections on the formed shape descriptors. Our network was trained on 533 patient cases and was validated on a set of out-of-sample cases. Results Our method generates heatmap predictions for isocenter locations that are in most cases comparable to the experienced human planners, which shows that the method can be used in treatment planning to guide the users for determining the isocenters. Conclusions Our numerical experiments indicate a positive predictive value on an independent validation set when compared against a test dataset that was not seen by the model during training.

OBJECTIVEPatients with arteriovenous malformations (AVMs) treated with Gamma Knife radiosurgery (GKRS) subsequent to embolization suffer from elevated local failure rates and differences in adverse radiation effects. Onyx is a common embolic material for AVMs. Onyx is formulated with tantalum, a high atomic number (Z = 73) element that has been investigated as a source of dosimetric uncertainty contributing to the less favorable clinical results. However, prior studies have not modeled the complicated anatomical and beam geometries characteristic of GKRS. This study investigated the magnitude of dose perturbation that can occur due to Onyx embolization using clinically realistic anatomical and Gamma Knife beam models.METHODSLeksell GammaPlan (LGP) was used to segment the AVM nidus and areas of Onyx from postcontrast stereotactic MRI for 7 patients treated with GKRS postembolization. The resulting contours, skull surface, and clinically selected dose distributions were exported from LGP in DICOM-RT (Digital Imaging and Communications in Medicine–radiotherapy) format. Isocenter locations and dwell times were recorded from the LGP database. Contours were converted into 3D mesh representations using commercial and in-house mesh-editing software. The resulting data were imported into a Monte Carlo (MC) dose calculation engine (Pegasos, Elekta Instruments AB) with a beam geometry for the Gamma Knife Perfexion. The MC-predicted dose distributions were calculated with Onyx assigned manufacturer-reported physical constants (MC-Onyx), and then compared with corresponding distributions in which Onyx was reassigned constants for water (MC-water). Differences in dose metrics were determined, including minimum, maximum, and mean dose to the AVM nidus; selectivity index; and target coverage. Combined differences in dose magnitude and distance to agreement were calculated as 3D Gamma analysis passing rates using tolerance criteria of 0.5%/0.5 mm, 1.0%/1.0 mm, and 3.0%/3.0 mm.RESULTSOverall, the mean percentage differences in dose metrics for MC-Onyx relative to MC-water were as follows; all data are reported as mean (SD): minimum dose to AVM = −0.7% (1.4%), mean dose to AVM = 0.1% (0.2%), maximum dose to AVM = 2.9% (5.0%), selectivity = 0.1% (0.2%), and coverage = −0.0% (0.2%). The mean percentage of voxels passing at each Gamma tolerance were as follows: 99.7% (0.1%) for 3.0%/3.0 mm, 98.2% (0.7%) for 1.0%/1.0 mm, and 52.1% (4.4%) for 0.5%/0.5 mm.CONCLUSIONSOnyx embolization appears to have a detectable effect on the delivered dose distribution. However, the small changes in dose metrics and high Gamma passing rates at 1.0%/1.0 mm tolerance suggest that these changes are unlikely to be clinically significant. Additional sources of delivery and biological uncertainty should be investigated to determine the root cause of the observed less favorable postembolization GKRS outcomes.

In the last decade, the concept of ‘global value chain’ (GVC) has become popular to describe the way firms fragment production into different stages located in different economies. The ‘made in the world’ narrative suggests that production today is global with inputs coming from all parts of the world before being assembled into final products also shipped all over the world. The empirical basis of this story has however been questioned. On the one hand, recent evidence indicates that there is some kind of ‘deglobalisation’ with a trade slowdown and lower levels of fragmentation of production. On the other hand, some authors suggest that supply chains are regional rather than global. In this paper, we offer a comprehensive review of the evidence based on the 2018 update of the OECD Trade in Value-Added (TiVA) database and indicators counting the number of domestic and foreign production stages, border crossings and geographic length of supply chains. The study covers 1995 to 2016. The made in the world narrative is correct when describing the rise of GVCs in the 2000s. But globalisation has reached a peak in 2012 and since then supply chains are becoming more domestic rather than more regional. The ‘erosion’ in globalisation (i.e. the reduction in the average length of supply chains since 2012) is 52 kilometres per year.

Stereotactic radiosurgery is an effective technique to treat brain tumors for which several inverse planning methods may be appropriate. We propose an integer programming model to simultaneous sector duration and isocenter optimization (SDIO) problem for Leksell Gamma Knife{\textregistered} Icon{\texttrademark} (Elekta, Stockholm, Sweden) to tractably incorporate treatment time. We devise a Benders decomposition scheme to solve the SDIO problem to optimality. The performances of our approaches are assessed using anonymized data from eight previously treated cases, and obtained treatment plans are compared against each other and against the clinical plans. The plans generated by our SDIO model all meet or exceed clinical guidelines while demonstrating high conformity.

Stereotactic radiosurgery (SRS) is an effective technique to treat brain metastasis for which several inverse planning methods may be appropriate. We compare three different optimization models for segment duration optimization in SRS using Leksell Gamma Knife® IconTM (Elekta, Stockholm, Sweden). We investigate (1) a linear programming approach, (2) a piecewise quadratic penalty approach, and (3) an unconstrained convex moment-based penalty approach. We examine the performances of these approaches using anonymized data from 14 previously treated cases. In addition, we investigate the important modeling question of selecting weights for the objective functions where we use a simulated annealing algorithm to determine these weights for each model. The inverse plans obtained via optimization models are compared against each other and against the clinical plans. The three inverse planning models can all yield optimal treatment plans in a reasonable amount of time and the treatment plans obtained by these models meet or exceed clinical guidelines while displaying high conformity.

A Contrast and Attenuation‐map Linearity Improvement (CALI) framework is proposed for cone‐beam CT (CBCT) images used for brain stereotactic radiosurgery (SRS). The proposed framework is tailored to improve soft tissue contrast of a new point‐of‐care image‐guided SRS system that employs a challenging half cone beam geometry, but can be readily reproduced on any CBCT platform. CALI includes a pre‐ and post‐processing step. In pre‐processing we apply a shading and beam hardening artifact correction to the projections, and in post‐processing step we correct the dome/capping artifact on reconstructed images caused by the spatial variations in X‐ray energy generated by the bowtie‐filter. The shading reduction together with the beam hardening and dome artifact correction algorithms aim to improve the linearity and accuracy of the CT‐numbers (CT#). The CALI framework was evaluated using CatPhan to quantify linearity, contrast‐to‐noise (CNR), and CT# accuracy, as well as subjectively on patient images acquired on a clinical system. Linearity of the reconstructed attenuation‐map was improved from 0.80 to 0.95. The CT# mean absolute measurement error was reduced from 76.1 to 26.9 HU. The CNR of the acrylic insert in the sensitometry module was improved from 1.8 to 7.8. The resulting clinical brain images showed substantial improvements in soft tissue contrast visibility, revealing structures such as ventricles which were otherwise undetectable in the original clinical images obtained from the system. The proposed reconstruction framework also improved CT# accuracy compared to the original images acquired on the system. For frameless image‐guided SRS, improving soft tissue visibility can facilitate evaluation of MR to CBCT co‐registration. Moreover, more accurate CT# may enable the use of CBCT for daily dose delivery measurements.

Measured by trade in intermediate inputs, economic integration has increased between 2000 and 2014 between members of the European Union and even more with non-members. Integration is negatively related to economic size and positively to the number of years as a member. Germany is the largest hub in the production network and the centre of gravity has moved eastward. Older member states are increasingly exporting service inputs and new member states primary and manufacturing inputs. Wages are increasing faster in countries with low initial wages, indicating wage convergence as a result of production integration.

A Contrast and Attenuation–map (CT-number) Linearity Improvement (CALI) framework is proposed for cone-beam CT (CBCT) images used for brain stereotactic radiosurgery (SRS). The proposed framework is used together with our high spatial resolution iterative reconstruction algorithm and is tailored for the Leksell Gamma Knife ICON (Elekta, Stockholm, Sweden). The incorporated CBCT system in ICON facilitates frameless SRS planning and treatment delivery. The ICON employs a half-cone geometry to accommodate the existing treatment couch. This geometry increases the amount of artifacts and together with other physical imperfections causes image inhomogeneity and contrast reduction. Our proposed framework includes a preprocessing step, involving a shading and beam-hardening artifact correction, and a post-processing step to correct the dome/capping artifact caused by the spatial variations in x-ray energy generated by bowtie-filter. Our shading correction algorithm relies solely on the acquired projection images (i.e. no prior information required) and utilizes filtered-back-projection (FBP) reconstructed images to generate a segmented bone and soft-tissue map. Ideal projections are estimated from the segmented images and a smoothed version of the difference between the ideal and measured projections is used in correction. The proposed beam-hardening and dome artifact corrections are segmentation free. The CALI was tested on CatPhan, as well as patient images acquired on the ICON system. The resulting clinical brain images show substantial improvements in soft contrast visibility, revealing structures such as ventricles and lesions which were otherwise un-detectable in FBP-reconstructed images. The linearity of the reconstructed attenuation-map was also improved, resulting in more accurate CT#.

A high spatial resolution iterative reconstruction algorithm is proposed for a half cone beam CT (HCBCT) geometry. The proposed algorithm improves spatial resolution by explicitly accounting for image blurriness caused by different factors, such as extended X-ray source and detector response. The blurring kernel is estimated using the MTF slice of the Catphan phantom. The proposed algorithm is specifically optimized for the new Leksell Gamma Knife Icon (Elekta AB, Stockholm, Sweden) which incorporates the HCBCT geometry to accommodate the existing treatment couch while covering down to the base-of-skull in the reconstructed field-of-view. Image reconstruction involves a Fourier-based scaling simultaneous algebraic reconstruction technique (SART) coupled with total variation (TV) minimization and non-local mean denoising, solved using a split Bregman separation technique that splits the reconstruction problem into a gradient based updating step and a TV-based deconvolution algorithm. This formulation preserves edges and reduces the staircase effect caused by regular TV-penalized iterative algorithms. Our experiments indicate that our proposed method outperforms the conventional filtered back projection and TV penalized SART methods in terms of line pair resolution and retains the favorable properties of the standard TV-penalized reconstruction.

Accurate determination of collimator output factors is important for Leksell Gamma Knife radiosurgery. The new Leksell Gamma Knife Perfexion system has a completely redesigned collimator system and the collimator output factors are different from the other Leksell Gamma Knife models. In this study, a simple method was developed to validate the collimator output factors specifically for Leksell Gamma Knife Perfexion. The method uses double-shot exposures on a single film to eliminate repeated setups and the necessity to acquire dose calibration curves required for the traditional film exposure method. Using the method, the collimator output factors with respect to the 16 mm collimator were measured to be 0.929 +/- 0.009 and 0.817 +/- 0.012 for the 8 mm and the 4 mm collimator, respectively. These values are in agreement (within 2%) with the default values of 0.924 and 0.805 in the Leksell Gamma Plan treatment planning system. These values also agree with recently published results of 0.917 (8 mm collimator) and 0.818 (4 mm collimator) obtained from the traditional methods. Given the efficiency of the method, measurement and validation of the collimator output factors can be readily adopted in commissioning and quality assurance of a Leksell Gamma Knife Perfexion system.

This investigation involves quantifying the extent of intracranial peripheral dose arising from simulated targets situated in the skull-base or upper-spine region using the Leksell GammaKnife® Perfexion™ treatment unit. For each of three spherical target volumes—denoted as V S ( 4 cm 3 ) , V M ( 18 cm 3 ) , and V L ( 60 cm 3 ) —three treatment plans were manually generated, one for each of the three collimator sizes—4, 8, and 16 mm. Each of the plans was delivered to a spherical dosimetry phantom with an insert containing EBT Gafchromic film. The total dose at 70 mm from the targets’ edges, % D ( 70 mm ) , was measured as a function of elevation angle and expressed as a percentage of the prescription dose. The film insert was placed centered in the median sagittal plane (Leksell X = 100 ) and % D ( 70 mm ) was measured for the angular range from 0° (superior/along Z axis) to 90° (anterior/along Y axis). For a given collimator i , the irradiation time t i to treat a spherical target of volume V using the 50% isodose line was observed to follow a power-law relationship of the form t i = A i ( V / V i ) n where A i was the maximum dose divided by collimatordose rate and V i was the volume encompassed by the 50% isodose line for a single shot. The mean value of n was 0.61 (range: 0.61–0.62). Along the superior ( Z ) direction ( angle = 0 ° ) and up to angles of around 30°, the % D ( 70 mm ) was always highest for the 4 mm plans, followed by the 8 mm, followed by the 16 mm. In this angular range, the maximum measured % D ( 70 mm ) was 1.7% of the prescription dose. The intracranial peripheral dose along the superior direction (combined scatter and leakage dose) resulting from irradiation of upper-spine or base-of-skull lesions is measured to be less than 2% of the prescription dose, even for very large ( 60 cm 3 ) targets. The results of this study indicate that, for a given target volume, treatment plans consisting of only 4 mm shots yield larger peripheral dose in the superior direction than 8 mm shot only plans, which in turn yield larger peripheral dose than 16 mm shot only plans.

The current dispute settlement system of the World Trade Organization (WTO) creates a particular challenge for WTO Members with limited exports since litigation costs are more or less independent of the commercial stakes involved in a dispute. Small Members with small trade stakes may therefore find it too costly to pursue legitimate claims. Reviewing the aims and practices of small claims procedures at the national and supranational level, we analyse whether a similar institution could be introduced at the WTO. While a strong empirical case can be made for such an innovation, the legal and political challenges should not be underestimated. As an initial step, we make a prima facie case that the current dispute settlement system effectively discriminates against small claims and hence owners of small claims, and thus, in particular, against least developed countries, small island economies and low income developing countries. This empirical task is carried out in Part 2. In Part 3 we explain what small claims procedures are at the national level, what purpose they serve, how they are organized in different jurisdictions involving alternative design features, and what challenges they have faced. Part 4 explores the issues raised by adding a small claims procedure in the WTO context, and indicates specific design features that could address them.

In the past five years, the concept of “global value chain” (GVC) has become popular to describe the way firms fragment production into different stages located in different economies. The “made in the world” narrative suggests that production today is global with inputs coming from all parts of the world before being assembled into final products also shipped all over the world. The empirical basis of this story has however been questioned, suggesting that supply chains are regional rather than global. In this paper we offer a comprehensive review of the evidence based on the World Input-Output Database (WIOD), including new indicators counting the number of domestic and foreign production stages, border crossings and geographic length of the supply chains. The study covers 1995 to 2011. All evidence points in the same direction. The made in the world narrative is correct as far as the direction is concerned, but we still have a long way to go. On average, globalization proceeds at 40 kilometres a year.

Magnetic resonance (MR) images lack information about radiation transport-a fact which is problematic in applications such as radiotherapy planning and attenuation correction in combined PET/MR imaging. To remedy this, a crude but common approach is to approximate all tissue properties as equivalent to those of water. We improve upon this using an algorithm that automatically identifies bone tissue in MR. More specifically, we focus on segmenting the skull prior to stereotactic neurosurgery, where it is common that only MR images are available. In the proposed approach, a machine learning algorithm known as a support vector machine is trained on patients for which both a CT and an MR scan are available. As input, a combination of local and global information is used. The latter is needed to distinguish between bone and air as this is not possible based only on the local image intensity. A whole skull segmentation is achievable in minutes. In a comparison with two other methods, one based on mathematical morphology and the other on deformable registration, the proposed method was found to yield consistently better segmentations.

Radiosurgery clinical practice relays on empirical observations and the experience of the practitioners involved in determining and delineating the target and therefore variability in target delineation might be expected for all the radiosurgery approaches, independent of the technique and the equipment used for delivering the treatment. The main aim of this study was to quantify the variability of target delineation for two radiosurgery targets expected to be difficult to delineate. The secondary aim was to investigate the dosimetric implications with respect to the plan conformity. The primary aim of the study has therefore a very general character, not being bound to one specific radiosurgery technique.Twenty radiosurgery centers were asked to delineate one cavernous sinus meningioma and one astrocytoma and to plan the treatments for Leksell Gamma Knife Perfexion. The analysis of the delineated targets was based on the calculated 50 % agreement volume, AV50. The AV50 was compared to each delineated target by the concordance index and discordance index. The differences in location, size, and shape of the delineated targets were also analyzed using the encompassing volume compared to the common volume, i.e., the AV100, of all delineated structures.Target delineation led to major differences between the participating centers and therefore the AV50 was small in comparison to each delineated target volume. For meningioma, the AV50 was 5.90 cm(3), the AV100 was 2.60 cm(3), and the encompassing volume was 13.14 cm(3). For astrocytoma, the AV50 was 2.06 cm(3) while the AV100 was extremely small, only 0.05 cm(3), and the encompassing volume was 43.27 cm(3). These variations translate into corresponding discrepancies in plan conformity.Significant differences in shape, size, and location between the targets included in this study were identified and therefore the clinical implications of these differences should be further investigated.

Variable levies on agricultural products are justified by policymakers as a protection against imported volatility. This position is challenged by economists who argue that variable levies accentuate the world market volatility and can only buy stability for some countries at the expense of others. As shown in this paper, it is possible to design a system of variable levies that protects against imported volatility without exporting the home-grown volatility. Thus, variable levies do not necessarily beggar thy neighbour.

Introduction The gains from trade in static models stem from the increased efficiency of resource allocation and improved consumption possibilities. With the addition of imperfect competition, gains from trade may also follow from pro-competitive effects related to increasing returns to scale, the erosion of market power, and increased product and input variety. Numerical estimates of basic static efficiency effects tend to be relatively small as a percentage of gross domestic product (GDP). For example, static assessments of the Tokyo Round and Uruguay Round typically pointed to income effects of less than 1 per cent of base GDP. This is hardly consistent with cross-country studies of trade and income, which suggest linkages between trade policy and incomes, through investment, much stronger than those identified in static numeric studies. Nor are such modest estimates easily reconciled with the expectations held about trade reforms of this magnitude. One shortcoming of the basic static story is that it fails to account for the positive relationship between trade, investment, and growth, a linkage that is fairly well established empirically (see, e.g., Edwards (1992), and Levine and Renelt (1992)). Also, on a theoretical level, classical growth theory suggests the potential for a medium-run growth or accumulation effect through induced changes in savings and investment patterns. The magnitude and possible direction of such effects depend on whether savings are assumed to be exogenously fixed or endogenously derived from intertemporal optimization. On the basis of this literature, we explore the interaction between trade policy and capital accumulation in a multi-sector, multi-country setting. The trade policy reforms considered are the basic elements of the Uruguay Round.

Background: Gamma knife surgery (GKS) is used at subnecrotic doses for temporal lobe epilepsy (TLE) treatment. Rat models of TLE have been used to probe the mechanisms underlying GKS. Previous GKS studies on rats have used the Leksell GammaPlan® (LGP) treatment planning system to determine the irradiation time to achieve the dose to deliver. Since LGP is not designed for such small structures, it is important to calibrate the system for the rat brain. Methods: We have used a Monte Carlo simulation (MCS) radiation transport scheme, with CT data as anatomical and tissue-specific information, to simulate the dose distribution in a rat brain when using a Leksell Gamma Knife®. Results: We show how dose distributions obtained by MCS quantitatively compare to those predicted by LGP, and discuss whether LGP should be used for studies involving rats. The energy deposited when using the 4-mm collimators was calculated for targets on both sides of the rat brain in the dorsal hippocampus, which allowed us to determine the exact time to irradiate rats with a given dose. Conclusion: The MCS method used in this study can easily be used for future GKS studies on small animals when accurate dose distributions are required.

This investigation involves quantifying the extent of intracranial peripheral dose arising from simulated targets situated in the skull-base or upper-spine region using the Leksell GammaKnife Perfexion treatment unit. For each of three spherical target volumes--denoted as Vs (4 cm3), VM (18 cm3), and VL (60 cm3)--three treatment plans were manually generated, one for each of the three collimator sizes--4, 8, and 16 mm. Each of the plans was delivered to a spherical dosimetry phantom with an insert containing EBT Gafchromic film. The total dose at 70 mm from the targets' edges, %D(70 mm), was measured as a function of elevation angle and expressed as a percentage of the prescription dose. The film insert was placed centered in the median sagittal plane (Leksell X = 100) and %D(70 mm) was measured for the angular range from 0 degree (superior/along Z axis) to 90 degrees (anterior/along Y axis). For a given collimator i, the irradiation time ti to treat a spherical target of volume V using the 50% isodose line was observed to follow a power-law relationship of the form ti = Ai(V/ Vi)n where Ai was the maximum dose divided by collimator dose rate and Vi was the volume encompassed by the 50% isodose line for a single shot. The mean value of n was 0.61 (range: 0.61-0.62). Along the superior (Z) direction (angle=0 degree) and up to angles of around 30 degrees, the %D(70 mm) was always highest for the 4 mm plans, followed by the 8 mm, followed by the 16 mm. In this angular range, the maximum measured %D(70 mm) was 1.7% of the prescription dose. The intracranial peripheral dose along the superior direction (combined scatter and leakage dose) resulting from irradiation of upper-spine or base-of-skull lesions is measured to be less than 2% of the prescription dose, even for very large (60 cm3) targets. The results of this study indicate that, for a given target volume, treatment plans consisting of only 4 mm shots yield larger peripheral dose in the superior direction than 8 mm shot only plans, which in turn yield larger peripheral dose than 16 mm shot only plans.

The current dispute settlement system of the WTO creates a particular challenge for WTO Members with limited exports because litigation costs are more or less independent of the commercial stakes involved in a dispute. Small Members with small trade stakes may therefore find it too costly to pursue legitimate claims. Reviewing the aims and practices of small-claims procedures at the national and supranational level, this chapter analyzes whether a similar institution could be introduced at the WTO. It makes a prima facie case that the current dispute settlement system effectively discriminates against small claims and hence owners of small claims, and thus, in particular, against least-developed countries, small-island economies, and low-income developing countries. It explains what small-claims procedures are at the national level, what purpose they serve, how they are organized in different jurisdictions involving alternative design features, and what challenges they have faced. The chapter also explores the issues raised by adding a small-claims procedure in the WTO context and indicates specific design features that could address them.

Purpose: To explore the possibility of separately quantifying the leakage and scatter components of the peripheral radiationdose resulting from Leksell GammaKnifeR Perfexion™ radiotherapy. Methods and Materials: In this study, peripheral dose was defined as the dose arising at points outside the paths of the primary beams. Consider a spherical skull phantom centered at Leksell coordinates (100,100,100). Peripheral dose may arise from: (1) Inphantom scatteredradiation originating from primary beams; (2) Radiation first scattered within the collimator structure (3) Photons undergoing multiple scattering and exiting through adjacent collimator openings and (4) Leakage radiation that passes directly through the collimator body. Contributions (1) and (2) were separately quantified via Monte‐Carlo simulations. Types (3) and (4) were measured using EBTII Gafchromic film inserts and placing the sources in“beam‐off” position (i.e. between collimator openings). Additionally, the total peripheral dose arising from a 16‐mm shot was measured using film. The combination of simulated type_1 and type_2 doses and measured type_3 and type_4 were compared to the measured total dose at 40 mm superior and inferior to the isocentre. Results: At the isocentre of the 16‐mm shot, the dose‐rate determined by Monte Carlo simulations agreed with measured dose‐rates to 0.8%, thereby establishing consistency between measurement and simulation. The simulated sum of Type_1 and Type_2 contributions at 40 mm inferior and superior to the isocentre was 0.40% and 0.35% of the isocentre dose‐rate, respectively. Of those totals, 87% was Type_1 a 13% came from Type 2. The measured total peripheral dose‐rate was 0.40% and 0.38% at 40 mm inferiorly and superiorly, respectively. The measured Type_3 and Type_4 dose‐rates were less than 0.01% of the isocentre dose‐rate in either direction. Conclusion: The results of this study indicate that peripheral dose arising from a single 16‐mm shot arises primarily from Type_1, with