Neapel, fotbollen och språket. Översättning av kulturella referenser och dialekt

Denna magisteruppsats grundar sig på två kapitel samt förordet i boken Il Napoli di Maradona. Cronistoria di un sogno: il primo scudetto av Gigi Garanzini och Marco Bellinazzo. Uppsatsen inleds med en analys av källtexten som utgår ifrån Hellspong & Ledins analysmodell (1997). Därefter följer en kortare redogörelse för de överväganden jag gjort inför översättningsarbetet, med utgångspunkt i Lita Lundquists lokala och globala översättningstrategier (2005), samt en översättningskommentar, där jag behandlar dialektala inslag och mottagaranpassning

Feasibility and constraints of Bragg peak FLASH proton therapy treatment planning

IntroductionFLASH proton therapy (FLASH-PT) requires ultra-high dose rate (≥ 40 Gy/s) protons to be delivered in a short timescale whilst conforming to a patient-specific target. This study investigates the feasibility and constraints of Bragg peak FLASH-PT treatment planning, and compares the in silico results produced to plans for intensity modulated proton therapy (IMPT).Materials and methodBragg peak FLASH-PT and IMPT treatment plans were generated for bone (n=3), brain (n=3), and lung (n=4) targets using the MIROpt research treatment planning system and the Conformal FLASH library developed by Applications SA from the open-source version of UCLouvain. FLASH-PT beams were simulated using monoenergetic spot-scanned protons traversing through a conformal energy modulator, a range shifter, and an aperture. A dose rate constraint of ≥ 40 Gy/s was included in each FLASH-PT plan optimisation.ResultsSpace limitations in the FLASH-PT adapted beam nozzle imposed a maximum target width constraint, excluding 4 cases from the study. FLASH-PT plans did not satisfy the imposed target dose constraints (D95% ≥ 95% and D2%≤ 105%) but achieved clinically acceptable doses to organs at risk (OARs). IMPT plans adhered to all target and OAR dose constraints. FLASH-PT plans showed a reduction in both target homogeneity (p < 0.001) and dose conformity (non-significant) compared to IMPT.ConclusionWithout accounting for a sparing effect, IMPT plans were superior in target coverage, dose conformity, target homogeneity, and OAR sparing compared to FLASH-PT. Further research is warranted in treatment planning optimisation and beam delivery for clinical implementation of Bragg peak FLASH-PT

Monitoring beam charge during FLASH irradiations

In recent years, FLASH irradiation has attracted significant interest in radiation research. Studies have shown that irradiation at ultra-high dose rates (FLASH) reduces the severity of toxicities in normal tissues compared to irradiation at conventional dose rates (CONV), as currently used in clinical practice. Most pre-clinical work is currently carried out using charged particle beams and the beam charge monitor described here is relevant to such beams. Any biological effect comparisons between FLASH and CONV irradiations rely on measurement of tissue dose. While well-established approaches can be used to monitor, in real time, the dose delivered during CONV irradiations, monitoring FLASH doses is not so straightforward. Recently the use of non-intercepting beam current transformers (BCTs) has been proposed for FLASH work. Such BCTs have been used for decades in numerous accelerator installations to monitor temporal and intensity beam profiles. In order to serve as monitoring dosimeters, the BCT output current must be integrated, using electronic circuitry or using software integration following signal digitisation. While sensitive enough for FLASH irradiation, where few intense pulses deliver the requisite dose, the inherent insensitivity of BCTs and the need for a wide detection bandwidth makes them less suitable for use during CONV “reference” irradiations. The purpose of this article is to remind the FLASH community of a different mode of BCT operation: direct monitoring of charge, rather than current, achieved by loading the BCT capacitively rather than resistively. The resulting resonant operation achieves very high sensitivities, enabling straightforward monitoring of output during both CONV and FLASH regimes. Historically, such inductive charge monitors have been used for single pulse work; however, a straightforward circuit modification allows selective resonance damping when repetitive pulsing is used, as during FLASH and CONV irradiations. Practical means of achieving this are presented, as are construction and signal processing details. Finally, results are presented showing the beneficial behaviour of the BCT versus an (Advanced Markus) ionisation chamber for measurements over a dose rate range, from <0.1 Gys−1 to >3 kGys−1

Conversion of helical tomotherapy plans to step-and-shoot IMRT plans-Pareto front evaluation of plans from a new treatment planning system

Purpose: The resulting plans from a new type of treatment planning system called SharePlan (TM) have been studied. This software allows for the conversion of treatment plans generated in a TomoTherapy system for helical delivery, into plans deliverable on C-arm linear accelerators (linacs), which is of particular interest for clinics with a single TomoTherapy unit. The purpose of this work was to evaluate and compare the plans generated in the SharePlan system with the original TomoTherapy plans and with plans produced in our clinical treatment planning system for intensity-modulated radiation therapy (IMRT) on C-arm linacs. In addition, we have analyzed how the agreement between SharePlan and TomoTherapy plans depends on the number of beams and the total number of segments used in the optimization. Methods: Optimized plans were generated for three prostate and three head-and-neck (H&N) cases in the TomoTherapy system, and in our clinical treatment planning systems (TPS) used for IMRT planning with step-and-shoot delivery. The TomoTherapy plans were converted into step-and-shoot IMRT plans in SharePlan. For each case, a large number of Pareto optimal plans were created to compare plans generated in SharePlan with plans generated in the Tomotherapy system and in the clinical TPS. In addition, plans were generated in SharePlan for the three head-and-neck cases to evaluate how the plan quality varied with the number of beams used. Plans were also generated with different number of beams and segments for other patient cases. This allowed for an evaluation of how to minimize the number of required segments in the converted IMRT plans without compromising the agreement between them and the original TomoTherapy plans. Results: The plans made in SharePlan were as good as or better than plans from our clinical system, but they were not as good as the original TomoTherapy plans. This was true for both the head-and-neck and the prostate cases, although the differences between the plans for the latter were small. The evaluation of the head-and-neck cases also showed that the plans generated in SharePlan were improved when more beams were used. The SharePlan Pareto front came close to the front for the TomoTherapy system when a sufficient number of beams were added. The results for plans generated with varied number of beams and segments demonstrated that the number of segments could be minimized with maintained agreement between SharePlan and TomoTherapy plans when 10-19 beams were used. Conclusions: This study showed (using Pareto front evaluation) that the plans generated in SharePlan are comparable to plans generated in other TPSs. The evaluation also showed that the plans generated in SharePlan could be improved with the use of more beams. To minimize the number of segments needed in a plan with maintained agreement between the converted IMRT plans and the original TomoTherapy plans, 10-19 beams should be used, depending on target complexity. SharePlan has proved to be useful and should thereby be a time-saving complement as a backup system for clinics with a single TomoTherapy system installed alongside conventional C-arm linacs. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3592934

Beam control system and output fine-tuning for safe and precise delivery of FLASH radiotherapy at a clinical linear accelerator

IntroductionWe have previously adapted a clinical linear accelerator (Elekta Precise, Elekta AB) for ultra-high dose rate (UHDR) electron delivery. To enhance reliability in future clinical FLASH radiotherapy trials, the aim of this study was to introduce and evaluate an upgraded beam control system and beam tuning process for safe and precise UHDR delivery.Materials and MethodsThe beam control system is designed to interrupt the beam based on 1) a preset number of monitor units (MUs) measured by a monitor detector, 2) a preset number of pulses measured by a pulse-counting diode, or 3) a preset delivery time. For UHDR delivery, an optocoupler facilitates external control of the accelerator’s thyratron trigger pulses. A beam tuning process was established to maximize the output. We assessed the stability of the delivery, and the independent interruption capabilities of the three systems (monitor detector, pulse counter, and timer). Additionally, we explored a novel approach to enhance dosimetric precision in the delivery by synchronizing the trigger pulse with the charging cycle of the pulse forming network (PFN).ResultsImproved beam tuning of gun current and magnetron frequency resulted in average dose rates at the dose maximum at isocenter distance of >160 Gy/s or >200 Gy/s, with or without an external monitor chamber in the beam path, respectively. The delivery showed a good repeatability (standard deviation (SD) in total film dose of 2.2%) and reproducibility (SD in film dose of 2.6%). The estimated variation in DPP resulted in an SD of 1.7%. The output in the initial pulse depended on the PFN delay time. Over the course of 50 measurements employing PFN synchronization, the absolute percentage error between the delivered number of MUs calculated by the monitor detector and the preset MUs was 0.8 ± 0.6% (mean ± SD).ConclusionWe present an upgraded beam control system and beam tuning process for safe and stable UHDR electron delivery of hundreds of Gy/s at isocenter distance at a clinical linac. The system can interrupt the beam based on monitor units and utilize PFN synchronization for improved dosimetric precision in the dose delivery, representing an important advancement toward reliable clinical FLASH trials

Comparable survival in rats with intracranial glioblastoma irradiated with single-fraction conventional radiotherapy or FLASH radiotherapy

BackgroundRadiotherapy increases survival in patients with glioblastoma. However, the prescribed dose is limited by unwanted side effects on normal tissue. Previous experimental studies have shown that FLASH radiotherapy (FLASH-RT) can reduce these side effects. Still, it is important to establish an equal anti-tumor efficacy comparing FLASH-RT to conventional radiotherapy (CONV-RT).MethodsFully immunocompetent Fischer 344 rats with the GFP-positive NS1 intracranial glioblastoma model were irradiated with CONV-RT or FLASH-RT in one fraction of 20 Gy, 25 Gy or 30 Gy. Animals were monitored for survival and acute dermal side effects. The brains were harvested upon euthanasia and tumors were examined post mortem.ResultsSurvival was significantly increased in animals irradiated with CONV-RT and FLASH-RT at 20 Gy and 25 Gy compared to control animals. The longest survival was reached in animals irradiated with FLASH-RT and CONV-RT at 25 Gy. Irradiation at 30 Gy did not lead to increased survival, despite smaller tumors. Tumor size correlated inversely with irradiation dose, both in animals treated with CONV-RT and FLASH-RT. Acute dermal side effects were mild, but only a small proportion of the animals were alive for evaluation of those side effects.ConclusionThe dose response was similar for CONV-RT and FLASH-RT in the present model. Tumor size upon the time of euthanasia correlated inversely with the irradiation dose

Haematological toxicity in adult patients receiving craniospinal irradiation - Indication of a dose-bath effect.

The purpose of this study was to investigate the correlation between the haematological toxicity observed in patients treated with craniospinal irradiation, and the dose distribution in normal tissue, specifically the occurrence of large volumes exposed to low dose

Evaluation of single-fraction high dose FLASH radiotherapy in a cohort of canine oral cancer patients

BackgroundFLASH radiotherapy (RT) is a novel method for delivering ionizing radiation, which has been shown in preclinical studies to have a normal tissue sparing effect and to maintain anticancer efficacy as compared to conventional RT. Treatment of head and neck tumors with conventional RT is commonly associated with severe toxicity, hence the normal tissue sparing effect of FLASH RT potentially makes it especially advantageous for treating oral tumors. In this work, the objective was to study the adverse effects of dogs with spontaneous oral tumors treated with FLASH RT.MethodsPrivately-owned dogs with macroscopic malignant tumors of the oral cavity were treated with a single fraction of ≥30Gy electron FLASH RT and subsequently followed for 12 months. A modified conventional linear accelerator was used to deliver the FLASH RT.ResultsEleven dogs were enrolled in this prospective study. High grade adverse effects were common, especially if bone was included in the treatment field. Four out of six dogs, who had bone in their treatment field and lived at least 5 months after RT, developed osteoradionecrosis at 3-12 months post treatment. The treatment was overall effective with 8/11 complete clinical responses and 3/11 partial responses.ConclusionThis study shows that single-fraction high dose FLASH RT was generally effective in this mixed group of malignant oral tumors, but the risk of osteoradionecrosis is a serious clinical concern. It is possible that the risk of osteonecrosis can be mitigated through fractionation and improved dose conformity, which needs to be addressed before moving forward with clinical trials in human cancer patients

A truncated Kv1.1 protein in the brain of the megencephaly mouse: expression and interaction

BACKGROUND: The megencephaly mouse, mceph/mceph, is epileptic and displays a dramatically increased brain volume and neuronal count. The responsible mutation was recently revealed to be an eleven base pair deletion, leading to a frame shift, in the gene encoding the potassium channel Kv1.1. The predicted MCEPH protein is truncated at amino acid 230 out of 495. Truncated proteins are usually not expressed since nonsense mRNAs are most often degraded. However, high Kv1.1 mRNA levels in mceph/mceph brain indicated that it escaped this control mechanism. Therefore, we hypothesized that the truncated Kv1.1 would be expressed and dysregulate other Kv1 subunits in the mceph/mceph mice. RESULTS: We found that the MCEPH protein is expressed in the brain of mceph/mceph mice. MCEPH was found to lack mature (Golgi) glycosylation, but to be core glycosylated and trapped in the endoplasmic reticulum (ER). Interactions between MCEPH and other Kv1 subunits were studied in cell culture, Xenopus oocytes and the brain. MCEPH can form tetramers with Kv1.1 in cell culture and has a dominant negative effect on Kv1.2 and Kv1.3 currents in oocytes. However, it does not retain Kv1.2 in the ER of neurons. CONCLUSION: The megencephaly mice express a truncated Kv1.1 in the brain, and constitute a unique tool to study Kv1.1 trafficking relevant for understanding epilepsy, ataxia and pathologic brain overgrowth