Šis darbas aprašo, atsižvelgiant į Lietuvos Respublikos teisės aktų reikalavimus ir vartotojų poreikius, sukurtą darbo laiko apskaitos žiniaraščio portalą ir su juo susijusią duomenų bazę, bei peržvelgia esančius analogiškus produktus. / Depending on the laws of the Republic of Lithuania requirements and the needs of users, the time sheets portal is made-up by this work and related database and the analogous products are reviewed.

Intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) have been introduced in radiation therapy to achieve highly conformal dose distributions around the tumour while minimizing dose to surrounding normal tissues. These techniques have increased the need for comprehensive quality assurance tests, to verify that customized patient treatment plans are accurately delivered during treatment. In vivo dose verification, performed during treatment delivery, confirms that the actual dose delivered is the same as the prescribed dose, helping to reduce treatment delivery errors. In vivo measurements may be accomplished using entrance or exit detectors. The objective of this project is to investigate a novel entrance detector designed for in vivo dose verification. This thesis is separated into three main investigations, focusing on a prototype entrance transmission detector (TRD) developed by IBA Dosimetry, Germany. First contaminant electrons generated by the TRD in a 6 MV photon beam were investigated using Monte Carlo (MC) simulation. This study demonstrates that modification of the contaminant electron model in the treatment planning system is required for accurate patient dose calculation in buildup regions when using the device. Second, the ability of the TRD to accurately measure dose from IMRT and VMAT was investigated by characterising the spatial resolution of the device. This was accomplished by measuring the point spread function with further validation provided by MC simulation. Comparisons of measured and calculated doses show that the spatial resolution of the TRD allows for measurement of clinical IMRT fields within acceptable tolerance. Finally, a new general research tool was developed to perform MC simulations for VMAT and IMRT treatments, simultaneously tracking dose deposition in both the patient CT geometry and an arbitrary planar detector system, generalized to handle either entrance or exit orientations. It was demonstrated that the tool accurately simulates dose to the patient CT and planar detector geometries. The tool has been made freely available to the medical physics research community to help advance the development of in vivo planar detectors. In conclusion, this thesis presents several investigations that improve the understanding of a novel entrance detector designed for patient in vivo dosimetry.

Radiation therapy is continuously increasing in complexity due to technological innovation in delivery techniques, necessitating thorough dosimetric verification. Comparing accurately predicted portal dose images to measured images obtained during patient treatment can determine if a particular treatment was delivered correctly. The goal of this thesis was to create a method to predict portal dose images that was versatile and accurate enough to use in a clinical setting. All measured images in this work were obtained with an amorphous silicon electronic portal imaging device (a-Si EPID), but the technique is applicable to any planar imager. A detailed, physics-motivated fluence model was developed to characterize fluence exiting the linear accelerator head. The model was further refined using results from Monte Carlo simulations and schematics of the linear accelerator. The fluence incident on the EPID was converted to a portal dose image through a superposition of Monte Carlo-generated, monoenergetic dose kernels specific to the a-Si EPID. Predictions of clinical IMRT fields with no patient present agreed with measured portal dose images within 3% and 3 mm. The dose kernels were applied ignoring the geometrically divergent nature of incident fluence on the EPID. A computational investigation into this parallel dose kernel assumption determined its validity under clinically relevant situations. Introducing a patient or phantom into the beam required the portal image prediction algorithm to account for patient scatter and attenuation. Primary fluence was calculated by attenuating raylines cast through the patient CT dataset, while scatter fluence was determined through the superposition of pre-calculated scatter fluence kernels. Total dose in the EPID was calculated by convolving the total predicted incident fluence with the EPID-specific dose kernels. The algorithm was tested on water slabs with square fields, agreeing with measurement within 3% and 3 mm. The method was then applied to five prostate and six head-and-neck IMRT treatment courses (~1900 clinical images). Deviations between the predicted and measured images were quantified. The portal dose image prediction model developed in this thesis work has been shown to be accurate, and it was demonstrated to be able to verify patients’ delivered radiation treatments.

In addition to the lonely battles fought by Bomber Command crews in the night skies over Germany from February 1942 to May 1945 there was an equally intense if much less bloody struggle in the halls of power between the Air Staff and the AOC Bomber Command, concerning the best employment of the strategic bomber forces. The argument of this study is that the Royal Air Force s contribution to the strategic air offensive was badly mismanaged: that Air Chief Marshal Sir Arthur Harris, Air Officer Commanding-in-Chief Bomber Command, from 22 February 1942 to the end of the war, by ignoring, or often over-riding the Air Staff, affected not only the course but also the duration of the Second World War. Most histories of the bomber war provide the result of the disagreements between the Chief of the Air Staff, Marshal of the Royal Air Force Sir Charles Portal and Harris, but rarely are the problems discussed in detail. This thesis examines the arguments that were raised by the various authorities, together with the refutations presented not only by the major participants, but also by the advisers to those authorities. The significant feature of the disagreements was that while Harris acted unilaterally, the Air Staff reached consensus decisions. Unfortunately, the decisions reached by the Air Staff on major issues were all too frequently either ignored or subverted by the AOC Bomber Command. One significant feature of the refutations presented to Harris was their dependence on the operational experience gained earlier in the bomber war by junior members of the Air Staff. For too long the direction of the war had been left in the hands of senior officers whose previous service had become irrelevant to war requirements in the 1940s. By 1942, comparatively junior officers were thus tendering advice to senior officers who, in the case of AOC Bomber Command, resented the authority which, Harris argued, had apparently been accorded these juniors. Harris was unable to accept that they were advisers and were never in a position to issue orders: orders could only come from Portal. Finally, this thesis provides an analysis of the strengths and weaknesses of the major participants and argues that, had the war been conducted as the Air Staff required, victory would have been achieved earlier than May 1945.

Öffentliche Bibliotheken stehen bei der Erfüllung ihres gesellschaftlichen Informationsund Bildungsauftrages in einer hochtechnisierten Wissensgesellschaft vor ganz neuen Herausforderungen. Die Bibliotheksentwicklungskonzeption (BEK) der Leipziger Städtischen Bibliotheken (LSB) ist Grundlage für Qualität und Quantität der Bibliotheksarbeit und reagiert in ihren regelmäßigen Fortschreibungen auf aktuelle Entwicklungen. Festgeschrieben sind darin auch der Ausbau der Online-Angebote und die Förderung des lebenslangen Lernens.

Am 9. Mai eröffnete Staatssekretär Dr. Knut Nevermann beim Sächsischen Bibliothekarstag in Schloss Forderglauchau das Bibliotheksportal Sachsen.

Intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) have been introduced in radiation therapy to achieve highly conformal dose distributions around the tumour while minimizing dose to surrounding normal tissues. These techniques have increased the need for comprehensive quality assurance tests, to verify that customized patient treatment plans are accurately delivered during treatment. In vivo dose verification, performed during treatment delivery, confirms that the actual dose delivered is the same as the prescribed dose, helping to reduce treatment delivery errors. In vivo measurements may be accomplished using entrance or exit detectors. The objective of this project is to investigate a novel entrance detector designed for in vivo dose verification. This thesis is separated into three main investigations, focusing on a prototype entrance transmission detector (TRD) developed by IBA Dosimetry, Germany. First contaminant electrons generated by the TRD in a 6 MV photon beam were investigated using Monte Carlo (MC) simulation. This study demonstrates that modification of the contaminant electron model in the treatment planning system is required for accurate patient dose calculation in buildup regions when using the device. Second, the ability of the TRD to accurately measure dose from IMRT and VMAT was investigated by characterising the spatial resolution of the device. This was accomplished by measuring the point spread function with further validation provided by MC simulation. Comparisons of measured and calculated doses show that the spatial resolution of the TRD allows for measurement of clinical IMRT fields within acceptable tolerance. Finally, a new general research tool was developed to perform MC simulations for VMAT and IMRT treatments, simultaneously tracking dose deposition in both the patient CT geometry and an arbitrary planar detector system, generalized to handle either entrance or exit orientations. It was demonstrated that the tool accurately simulates dose to the patient CT and planar detector geometries. The tool has been made freely available to the medical physics research community to help advance the development of in vivo planar detectors. In conclusion, this thesis presents several investigations that improve the understanding of a novel entrance detector designed for patient in vivo dosimetry.

Radiation therapy is continuously increasing in complexity due to technological innovation in delivery techniques, necessitating thorough dosimetric verification. Comparing accurately predicted portal dose images to measured images obtained during patient treatment can determine if a particular treatment was delivered correctly. The goal of this thesis was to create a method to predict portal dose images that was versatile and accurate enough to use in a clinical setting. All measured images in this work were obtained with an amorphous silicon electronic portal imaging device (a-Si EPID), but the technique is applicable to any planar imager. A detailed, physics-motivated fluence model was developed to characterize fluence exiting the linear accelerator head. The model was further refined using results from Monte Carlo simulations and schematics of the linear accelerator. The fluence incident on the EPID was converted to a portal dose image through a superposition of Monte Carlo-generated, monoenergetic dose kernels specific to the a-Si EPID. Predictions of clinical IMRT fields with no patient present agreed with measured portal dose images within 3% and 3 mm. The dose kernels were applied ignoring the geometrically divergent nature of incident fluence on the EPID. A computational investigation into this parallel dose kernel assumption determined its validity under clinically relevant situations. Introducing a patient or phantom into the beam required the portal image prediction algorithm to account for patient scatter and attenuation. Primary fluence was calculated by attenuating raylines cast through the patient CT dataset, while scatter fluence was determined through the superposition of pre-calculated scatter fluence kernels. Total dose in the EPID was calculated by convolving the total predicted incident fluence with the EPID-specific dose kernels. The algorithm was tested on water slabs with square fields, agreeing with measurement within 3% and 3 mm. The method was then applied to five prostate and six head-and-neck IMRT treatment courses (~1900 clinical images). Deviations between the predicted and measured images were quantified. The portal dose image prediction model developed in this thesis work has been shown to be accurate, and it was demonstrated to be able to verify patients’ delivered radiation treatments.

A technique for the in vivo dose verification of intensity modulated radiation therapy (IMRT) has been developed. An electronic portal image, calibrated in terms of absolute dose, is acquired for each radiation field following transmission through the patient at the time of treatment. For an IMRT field, the portal image signal is back-projected through a model of the patient in order to calculate the dose at the isocentric plane perpendicular to the beam central axis. The IMRT in vivo dose verification technique was adapted for volumetric modu- lated arc therapy (VMAT) treatments when a single dosimetric image is acquired over an arc. The patient dose along axis of gantry rotation can be directly related to the signal along the vertical axis of EPIs in integrated mode. In this novel VMAT in vivo dosimetry technique, the portal image signal is back-projected through a rotationally averaged model of the patient to calculate a 1D in vivo dose along the axis of gantry rotation. A research ethics board clinical study was approved and transmission portal images were acquired at regular intervals from human subjects. Portal image-derived isocenter point doses were in good agreement with treatment planning system (TPS) calculations for IMRT (mean difference δ=0.0%, standard deviation of the differences σ=4.3%) and VMAT (δ=1.1%, σ=1.7%). The one-dimensional (VMAT) and two-dimensional (IMRT) reconstructed doses were further analyzed by calculating mean dose differences and γ−evaluation pass-rates, which were also shown to be in good agreement with TPS calculations. The portal image-based in vivo dosimetry techniques were shown to be clinically feasible, with reconstruction times on the order of minutes for the first fraction and less than one minute for each fraction thereafter. / Graduate / 0760 / 0574 / 0760

La hipertensió portal és una síndrome clínica que representa la principal complicació de la cirrosi hepàtica i es caracteritza per un increment patològic de la pressió hidrostàtica del sistema venós portal. Bona part de les complicacions derivades de la cirrosi hepàtica, estan directament relacionades amb la presència d'hipertensió portal clínicament significativa. A causa de la gravetat d'aquestes complicacions, la hipertensió portal representa la primera causa de morbimortalitat en malalts cirròtics.La pressió portal ve determinada per la interrelació entre el flux sanguini portal i la resistència que s'oposa a aquest flux. L'augment de la resistencia vascular intrahepàtica (RVI) constitueix el fenomen fisiopatològic primari de la hipertensió portal.Amb l'objectiu de caracteritzar el component dinàmic de la RVI, s'han estudiat quins són els elements contràctils intrahepàtics i si en la cirrosi existeixen anormalitats en la regulació dels mecanismes de contracció cel·lular. Fins a l'actualitat s'han descrit diversos tipus de cèl·lules hepàtiques amb capacitat contràctil com els miofibroblasts portals i septals i les vènules portals, però majoritàriament s'ha postulat que les principals cèl·lules involucrades en la regulació del to vascular hepàtic són les cèl·lules hepàtiques estrellades.S'han descrit un ampli ventall de molècules amb capacitat vasomotora com a moduladores de la RVI en la cirrosi. Aquestes substàncies poden procedir de la circulació sistèmica (com l'angiotensina II o la vasopressina), poden originar-se a l'endoteli i actuar de forma paracrina (com l'òxid nítric (ON), la prostaciclina (PGI2) o l'endotelina) o tenir un origen neuronal (norepinefrina).El to vascular en condicions normals és el resultat d'un delicat balanç entre diversos mediadors vasoactius. En la circulació hepàtica en la cirrosi existeix un marcat desequilibri en la producció i concentració d'aquests mediadors vasoactius: els nivells de vasoconstrictors es troben elevats (com l'endotelina o el prostanoid derivat de la ciclooxigenasa 1 (COX-1): tromboxà A2) i els nivells de vasodilatadors estan reduïts (principalment l'ON). A més, s'ha demostrat que els fetges cirròtics presenten una hiperresposta als estímuls vasoconstrictors i una hiporesposta als vasodilatadors.S'ha demostrat que en el fetge cirròtic, la biodisponibilitat d'ON es troba disminuïda, la qual cosa es considera un factor fonamental per a promoure l'augment de RVI.Diversos estudis, a través d'estratègies experimentals ben diferents, han aconseguit incrementar la producció hepàtica d'ON reduint així la RVI i la pressió portal de rates amb cirrosi sense modificar la pressió arterial.En els últims anys s'ha posat de manifest el paper de l'estrès oxidatiu i de les ROS en el control del to vascular i en el desenvolupament de disfunció endotelial de diverses malalties vasculars com la hipertensió, l'arteriosclerosi o la diabetes. L'estrès oxidatiu també juga un paper fisiopatològic en la progressió de malalties hepàtiques. Una altra qüestió important de les ROS, concretament de l'anió O2-, és la seva capacitat per a reaccionar amb l'ON, donant lloc a la producció de ONOO-, contribuint així a disminuir la biodisponibilitat d'ON. El paper de l'estrès oxidatiu i la seva capacitat per modular la biodisponibilitat d'ON, així com l'ús terapèutic d'antioxidants en diverses malalties vasculars, ha estat àmpliament avaluat per nombrosos estudis en pacients i en models experimentals. En canvi, en la hipertensió portal en la cirrosi, aquests elements ho han estat avaluats. Els treballs de recerca de la present tesi estan globalment orientats a ampliar el coneixement dels mecanismes moleculars responsables de l'augment del component dinàmic de la RVI en la cirrosi, concretament el paper de l'estrès oxidatiu i la seva implicació en la modulació de la biodisponibilitat d'ON. Articles tesi:1. Increased oxidative stress in cirrhotic rat livers: A potential mechanism contributing to reduce nitric oxide bioavailability.Gracia-Sancho J*, Laviña B*, Rodríguez-Vilarrupla A, García-Calderó H, Fernández M, Bosch J, García-Pagán JC.Hepatology 2008 Apr;47(4):1248-56. 2. Superoxide dismutase gene transfer reduces portal pressure in CCl4 cirrhotic rats with portal hypertensionLaviña B, Gracia-Sancho J, Rodríguez-Vilarrupla A, Chu Y, Hesitad DD, Bosch J, García-Pagán JC. Gut 2009; 58: 118-125. / Increased resistance to portal blood flow is the primary factor in the pathophysiology of portal hypertension, the main complication of cirrhosis. Architectural alterations of the liver parenchyma, but also a dynamic increase in the hepatic vascular tone contribute to the increased resistance to portal blood flow of cirrhotic livers. The increase in hepatic vascular tone is partly due to increased release of cyclooxygenase-1 (COX-1)-derived vasoconstrictive prostanoids and to a reduced bioavailability within the liver of the potent vasodilator nitric oxide (NO). Both mechanisms favouring the contraction of different elements within the cirrhotic liver. Indeed, activated hepatic stellate cells have been shown to contract or relax in response to vasoconstrictive prostanoids or NO respectively.Reduced NO bioavailability has been attributed to decreased endothelial nitric oxide synthase (eNOS) activity secondary to several disturbances in the posttranslational regulation of the enzyme.In several vascular disorders the potential of ROS to bind proteins, break DNA and promote cell damage by reacting with several cellular components has been involved in development of necrosis, inflammation, and apoptosis. In addition, an increase in the reactive oxygen specie superoxide (O2-), by rapidly reacting with NO, promotes a marked reduction in NO bioavailability followed by an increase in vascular tone.An increase in O2- levels due to increased production by xanthine oxidase (XO), NADPH oxidase or COX, among other enzymatic systems, and a reduced O2- scavenging by superoxide dismutase has been suggested to play a pathophysiological role in different liver disorders such as in alcoholic and non-alcoholic liver disease.Gene transfer of SOD has been shown to protect against oxidative stress and to improve endothelium-dependent relaxation in several situations, including myocardial infarction, liver transplantation, hypertension, diabetes , and aging. We hypothesize that in cirrhotic livers increased O2-, by reacting with NO, would contribute to reduce NO bioavailability. As a consequence, removing O2- from the cirrhotic livers could be a new therapeutic strategy to improve intrahepatic NO bioavailability, improve hepatic endothelial dysfunction and reduce portal pressure in rats with cirrhosis and portal hypertension.