Analyzing the modulation effects of lung tissue in proton therapy

Non-small cell lung cancer (NSCLC) is the number one cause of cancer-related deaths worldwide. Furthermore, it is predicted that the incidence and mortality will further increase due to smoking, increasing pollution of the environment, and an aging population. For patients unable to undergo surgery corresponding radiotherapy concepts are necessary. However, due to the vicinity of critical organs like the heart, esophagus, trachea, larger blood vessels, and the spinal cord a dose escalation is not always easily achievable using photon-based radiotherapy. Proton therapy (PT) has the potential to deposit a conformal dose in the target volume while better sparing surrounding normal tissue and hence could be beneficial for lung cancer patients. However, there are various challenges connected to proton therapy in general and proton therapy of lung cancer patients in particular. One of these challenges arises from the structure of the lung tissue itself: due to the microscopic density heterogeneity the proton dose distribution is degraded resulting in a broader Bragg peak and a wider distal dose fall-off. This modulation effect can significantly influence the dose distribution in patients resulting in a lower dose deposited in the target volume and higher doses deposited in distal normal tissue and organs at risk (OAR). Since the microscopic structure of the lung tissue is not fully resolved in clinical treatment-planning CT-images, a consideration of the Bragg peak degradation is not possible with current state-of-the-art treatment-planning systems (TPS). In this dissertation, a mathematical model is used to describe the effects due to the Bragg peak degradation. The strength of the degradation is quantified using the material characteristic "modulation power". Microscopic heterogeneous voxelized geometries are used to generate degraded dose distributions with the help of Monte Carlo (MC) simulations. Subsequently, these geometries representing human lung tissue are replaced by clinical voxels with an edge length of 2 mm. Hence, the transition from the microscopic lung tissue as it is present in the patient to coarser clinical CT-structures that cannot resolve the fine lung structure is performed. By modulating the density of each clinical voxel the Bragg peak degradation can be reproduced. Hence, a solution is found to reproduce the lung modulation effects on clinical CT-images. Using this technique, a CT-based phantom study was designed to estimate the effects of the Bragg peak degradation for realistic patient anatomies. Different tumor volumes located at different depths in the lung were investigated. It was shown that, if the lung modulation effects are not accounted for during the treatment-planning process, the dose deposited in the target volume is overestimated and the dose deposited in distal normal tissue is underestimated. This effect increases with an increasing depth of the tumor in lung and a decreasing extent of the tumor in beam direction. At last, the effects were investigated for clinical treatment plans for lung cancer patients. The overestimation of the mean dose in the CTV was 5% at maximum and in the order of 2% on average. The effect on OARs distal to the target volume was negligible for all cases investigated. The investigation of treatment plans confirms that the lung modulation effects are clinically tolerable to a certain degree in the current clinical context considering the various more critical dose uncertainties due to motion and range uncertainties in proton therapy. Nevertheless, PTV concepts were presented that could compensate for the lung modulation effects

Monte Carlo calculated ionization chamber correction factors in clinical proton beams – deriving uncertainties from published data

For the update of the IAEA TRS-398 Code of Practice (CoP), global ionization chamber factors (fQ) and beam quality correction factors (kQ) for air-filled ionization chambers in clinical proton beams have been calculated with different Monte Carlo codes. In this study, average Monte Carlo calculated fQ and kQ factors are provided and the uncertainty of these factors is estimated. Average fQ factors in monoenergetic proton beams with energies between 60 MeV and 250 MeV were derived from Monte Carlo calculated fQ factors published in the literature. Altogether, 195 fQ factors for six plane-parallel and three cylindrical ionization chambers calculated with PENH, FLUKA and GEANT4 were incorporated. Additionally, a weighted standard deviation of fQ factors was calculated, where the same weight was assigned to each Monte Carlo code. From average fQ factors, kQ factors were derived and compared to the values from the IAEA TRS-398 CoP published in 2000 as well as to the values of the upcoming version. Average Monte Carlo calculated fQ factors are constant within 0.6% over the energy range investigated. In general, the different Monte Carlo codes agree within 1% for low energies and show larger differences up to 2% for high energies. As a result, the standard deviation of fQ factors increases with energy and is ∼0.3% for low energies and ∼0.8% for high energies. kQ factors derived from average Monte Carlo calculated fQ factors differ from the values presented in the IAEA TRS-398 CoP by up to 2.4%. The overall estimated uncertainty of Monte Carlo calculated kQ factors is ∼0.5%–1% smaller than the uncertainties estimated in IAEA TRS-398 CoP since the individual ionization chamber characteristics (e.g. fluence perturbations) are considered in detail in Monte Carlo calculations. The agreement between Monte Carlo calculated kQ factors and the values of the upcoming version of IAEA TRS-398 CoP is better with deviations smaller than 1%.</p

Validierung und Reliabilitätsprüfung des Nijmegen Cochlear Implant Questionnaire in deutscher Sprache

Hintergrund: Der Nijmegen Cochlear Implant Questionnaire (NCIQ) ist ein krankheitsspezifischer Fragebogen zur Erhebung der gesundheitsbezogenen Lebensqualität von Patienten vor und nach Cochleaimplantation. Ziel der Arbeit: Validierung und Reliabilitätsprüfung der deutschen Übersetzung des NCIQ. Material und Methoden: Es wurde eine prospektive Studie an 100 postlingual ertaubten oder hochgradig schwerhörigen Patienten durchgeführt, welche präoperativ sowie 3 und 6 Monate nach einer Cochleaimplantation mittels NCIQ, Abbreviated Profile of Hearing Aid Benefit (APHAB) und Hearing Participation Scale (HPS) untersucht wurden. Als Kontrolle fungierte ein postlingual ertaubtes oder hochgradig schwerhöriges, unbehandeltes Patientenkollektiv (n = 54). Cronbach‑α und Test-Retest-Reliabilität dienten der Reliabilitätsüberprüfung. Es wurde auf Inhalts‑, Übereinstimmungs- und auf diskriminative Validität getestet. Die Konstruktvaliditätsprüfung basiert auf kürzlich veröffentlichen Daten. Als Gütekriterien wurden die Sensitivität und eine ROC("Receiver Operating Characteristic")-Analyse, inklusive AUC("Area Under the ROC Curve")-Betrachtung, eingesetzt. Ergebnisse: Das Test-Retesting ergab nach 3 und 6 Monaten postoperativ stabile NCIQ-Werte. Die Cronbach-α-Werte wiesen auf eine gute interne Konsistenz hin. Der NCIQ diskriminierte valide zwischen behandelten und unbehandelten Patientengruppen. Es ergaben sich statistisch signifikante, wenn auch schwache, Korrelationen zwischen dem NCIQ und dem APHAB (r = -0,22; p = 0,04) und dem HPS (r = 0,30; p = 0,01). Sensitivitäts- und ROC-Analysen zeigten eine gute Messqualität des deutschsprachigen NCIQ. Schlussfolgerung: Die deutsche Übersetzung des NCIQ misst zuverlässig und valide die Lebensqualität vor und nach Cochleaimplantation und kann zur klinischen Erfolgskontrolle nach Cochleaimplantationen verwendet werden.Background: The Nijmegen Cochlear Implant Questionnaire (NCIQ) is a disease-specific questionnaire to determine the health-related quality of life (HRQoL) of patients before and after cochlear implantation. Objective: This study aimed to assess the validity and reliability of the German translation of the NCIQ. Materials and methods: A prospective study was performed in 100 postlingually deaf or severely hearing-impaired patients. HRQoL was assessed using the NCIQ, the Abbreviated Profile of Hearing Aid Benefit (APHAB), and the Hearing Participation Scale (HPS) before as well as 3 and 6 months after cochlear implantation. An untreated group of postlingually deaf or severely hearing-impaired patients (n = 54) served as a control. Cronbach's α and test–retest reliability were measured. The content, discrimination, and agreement validity were tested. The evaluation of construct validity was based on recently published data. Sensitivity and receiver operating curve (ROC) analysis, including consideration of the area under the curve (AUC), were used as quality criteria. Results: The test-retest analysis showed stable NCIQ values 3 and 6 months postoperatively. The Cronbach’s α values indicated good internal consistency. The NCIQ validly discriminated between treated and untreated patient groups. There were statistically significant albeit weak correlations between the NCIQ and the APHAB (r = -0.22; p = 0.04) and the HPS (r = 0.30; p = 0.01). Sensitivity and ROC analyses showed good measurement quality of the German-speaking NCIQ. Conclusion: The German translation of the NCIQ reliably and validly measures HRQoL before and after cochlear implantation and can be used for clinical monitoring after treatment with cochlear implants

heiMAP – Virtual Research Environment for collaborative spatio-temporal research in the Humanities

heiMAP is a Virtual Research Environment (VRE) for research in the Humanities that facilitates collaborative work in spatio-temporal contexts. The differentiating characteristic of heiMAP is its holistic approach, representing the entire scientific data lifecycle. This includes the generation of, as well as discourse about, spatio-temporal data, their publication, archiving and sustainable reuse. The VRE consists of an Open Source Content Management System (CMS) that handles data and research projects, and an integrated Web Geographic Information Systems (GIS) application used to contextualize vector and raster data, especially maps. By sticking to international standards (OGC, CIDOC CRM among others), we strive for a maximum of data interoperability and reusability of the data produced within heiMAP. Close cooperation with the Heidelberg University Library and Heidelberg Computing Center allows for the publication, referenced by a Digital Object Identifier (DOI), as well as the long-term archiving of individual research projects and their related outcomes. One major challenge in building an environment for collaborative research is to ensure that users retain control over their data where necessary but are also enabled to share it with others when they wish to. Therefore, heiMAP possesses a sophisticated system for user and rights management as well as fine-grained control of user rights based on the CMS. To allow a broad range of users from different parts of the Humanities (including both University and Citizen Science projects) with varying degrees of expertise in spatial research and GIS, to effectively use heiMAP, the platform focuses on a number of core functions while allowing export of research data into more sophisticated desktop-based GIS programs when necessary

Overview: On the transport and transformation of pollutants in the outflow of major population centres – observational data from the EMeRGe European intensive operational period in summer 2017

Megacities and other major population centres (MPCs) worldwide are major sources of air pollution, both locally as well as downwind. The overall assessment and prediction of the impact of MPC pollution on tropospheric chemistry are challenging. The present work provides an overview of the highlights of a major new contribution to the understanding of this issue based on the data and analysis of the EMeRGe (Effect of Megacities on the transport and transformation of pollutants on the Regional to Global scales) international project. EMeRGe focuses on atmospheric chemistry, dynamics, and transport of local and regional pollution originating in MPCs. Airborne measurements, taking advantage of the long range capabilities of the High Altitude and LOng Range Research Aircraft (HALO, https://www.halo-spp.de, last access: 22 March 2022), are a central part of the project. The synergistic use and consistent interpretation of observational data sets of different spatial and temporal resolution (e.g. from ground-based networks, airborne campaigns, and satellite measurements) supported by modelling within EMeRGe provide unique insight to test the current understanding of MPC pollution outflows. In order to obtain an adequate set of measurements at different spatial scales, two field experiments were positioned in time and space to contrast situations when the photochemical transformation of plumes emerging from MPCs is large. These experiments were conducted in summer 2017 over Europe and in the inter-monsoon period over Asia in spring 2018. The intensive observational periods (IOPs) involved HALO airborne measurements of ozone and its precursors, volatile organic compounds, aerosol particles, and related species as well as coordinated ground-based ancillary observations at different sites. Perfluorocarbon (PFC) tracer releases and model forecasts supported the flight planning, the identification of pollution plumes, and the analysis of chemical transformations during transport. This paper describes the experimental deployment and scientific questions of the IOP in Europe. The MPC targets – London (United Kingdom; UK), the Benelux/Ruhr area (Belgium, the Netherlands, Luxembourg and Germany), Paris (France), Rome and the Po Valley (Italy), and Madrid and Barcelona (Spain) – were investigated during seven HALO research flights with an aircraft base in Germany for a total of 53 flight hours. An in-flight comparison of HALO with the collaborating UK-airborne platform Facility for Airborne Atmospheric Measurements (FAAM) took place to assure accuracy and comparability of the instrumentation on board. Overall, EMeRGe unites measurements of near- and far-field emissions and hence deals with complex air masses of local and distant sources. Regional transport of several European MPC outflows was successfully identified and measured. Chemical processing of the MPC emissions was inferred from airborne observations of primary and secondary pollutants and the ratios between species having different chemical lifetimes. Photochemical processing of aerosol and secondary formation or organic acids was evident during the transport of MPC plumes. Urban plumes mix efficiently with natural sources as mineral dust and with biomass burning emissions from vegetation and forest fires. This confirms the importance of wildland fire emissions in Europe and indicates an important but discontinuous contribution to the European emission budget that might be of relevance in the design of efficient mitigation strategies. The present work provides an overview of the most salient results in the European context, with these being addressed in more detail within additional dedicated EMeRGe studies. The deployment and results obtained in Asia will be the subject of separate publications

Language endangerment and language documentation in Africa

Non peer reviewe

Overview: On the transport and transformation of pollutants in the outflow of major population centres – observational data from the EMeRGe European intensive operational period in summer 2017

Megacities and other major population centres (MPCs) worldwide are major sources of air pollution, both locally as well as downwind. The overall assessment and prediction of the impact of MPC pollution on tropospheric chemistry are challenging. The present work provides an overview of the highlights of a major new contribution to the understanding of this issue based on the data and analysis of the EMeRGe (Effect of Megacities on the transport and transformation of pollutants on the Regional to Global scales) international project. EMeRGe focuses on atmospheric chemistry, dynamics, and transport of local and regional pollution originating in MPCs. Airborne measurements, taking advantage of the long range capabilities of the High Altitude and LOng Range Research Aircraft (HALO, https://www.halo-spp.de, last access: 22 March 2022), are a central part of the project. The synergistic use and consistent interpretation of observational data sets of different spatial and temporal resolution (e.g. from ground-based networks, airborne campaigns, and satellite measurements) supported by modelling within EMeRGe provide unique insight to test the current understanding of MPC pollution outflows. In order to obtain an adequate set of measurements at different spatial scales, two field experiments were positioned in time and space to contrast situations when the photochemical transformation of plumes emerging from MPCs is large. These experiments were conducted in summer 2017 over Europe and in the inter-monsoon period over Asia in spring 2018. The intensive observational periods (IOPs) involved HALO airborne measurements of ozone and its precursors, volatile organic compounds, aerosol particles, and related species as well as coordinated ground-based ancillary observations at different sites. Perfluorocarbon (PFC) tracer releases and model forecasts supported the flight planning, the identification of pollution plumes, and the analysis of chemical transformations during transport. This paper describes the experimental deployment and scientific questions of the IOP in Europe. The MPC targets – London (United Kingdom; UK), the Benelux/Ruhr area (Belgium, the Netherlands, Luxembourg and Germany), Paris (France), Rome and the Po Valley (Italy), and Madrid and Barcelona (Spain) – were investigated during seven HALO research flights with an aircraft base in Germany for a total of 53 flight hours. An in-flight comparison of HALO with the collaborating UK-airborne platform Facility for Airborne Atmospheric Measurements (FAAM) took place to assure accuracy and comparability of the instrumentation on board. Overall, EMeRGe unites measurements of near- and far-field emissions and hence deals with complex air masses of local and distant sources. Regional transport of several European MPC outflows was successfully identified and measured. Chemical processing of the MPC emissions was inferred from airborne observations of primary and secondary pollutants and the ratios between species having different chemical lifetimes. Photochemical processing of aerosol and secondary formation or organic acids was evident during the transport of MPC plumes. Urban plumes mix efficiently with natural sources as mineral dust and with biomass burning emissions from vegetation and forest fires. This confirms the importance of wildland fire emissions in Europe and indicates an important but discontinuous contribution to the European emission budget that might be of relevance in the design of efficient mitigation strategies. The present work provides an overview of the most salient results in the European context, with these being addressed in more detail within additional dedicated EMeRGe studies. The deployment and results obtained in Asia will be the subject of separate publications