Search

BACKGROUND: Thymomas are characterized by a low tumor mutation burden and a paucity of actionable mutations. Clinical behavior can vary from relatively indolent to very aggressive and impact survival. Platinum-based chemotherapy is the primary treatment modality for inoperable disease and is palliative in intent. Patients with advanced thymoma frequently experience disease recurrence after frontline therapy. Treatment options for relapsed thymoma are relatively limited. A case of recurrent thymoma harboring a breast cancer gene 2 (BRCA2) mutation was presented for multidisciplinary discussion at the International Thymic Malignancy Interest Group (ITMIG) Tumor Board meeting. CASE DESCRIPTION: A 63-year-old female presented with Tumor Node Metastasis (TNM) stage I, World Health Organization (WHO) subtype B1 thymoma at diagnosis and underwent surgical resection. First recurrence occurred in the left costophrenic recess and was treated with preoperative external beam radiotherapy (EBRT), surgical excision, and post-operative chemotherapy. Histology was consistent with WHO subtype B2 thymoma and genomic analysis of the resected tumor detected a BRCA2 mutation. Second recurrence occurred in the mediastinum and bilateral pleurae. Mediastinal disease was treated with EBRT, and the pleural deposits were observed initially. However, upon further progression, the case was discussed at the ITMIG tumor board meeting to determine optimal second line therapy for this patient. CONCLUSIONS: A potential role of poly (ADP-ribose) polymerase (PARP) inhibitors versus cytotoxic chemotherapy for treatment of BRCA2-mutated recurrent thymoma merits discussion. However, due to the absence of data to support the functional and therapeutic significance of BRCA2 mutations in patients with thymoma, the potential for severe toxicity associated with PARP inhibitors, and availability of other safe and effective alternatives, other treatment options should be considered. PARP inhibitors can be consi

Purpose Our purpose was to assess the suitability of airway-implanted internal fiducial markers and an external surrogate of respiratory motion for motion management during radiation therapy of lung tumors. Methods and Materials We analyzed 4-dimensional computed tomography scans acquired during radiation therapy simulation for 28 patients with lung tumors who had anchored fiducial markers bronchoscopically implanted inside small airways in or near the tumor in a prospective trial. We used a linear mixed model to build population-based correlative models of tumor and surrogate motion. The first 24 of the 28 patients were used to build correlative models, and 4 of the 28 consecutive patients were excluded and used as an internal validation cohort. Of the 24 patients from the model building cohort, all were used for the models based on the internal fiducial. The external surrogate was completely visualized in 11 patients from the model building cohort, so only those were used for the models based on the external surrogate. Furthermore, we determined the predicted residual error sum of squares for our correlative models, which may serve as benchmarks for future research. Results The motion of the internal fiducials was significantly associated with the tumor motion in the anterior-posterior (P < .0001) and superior-inferior (SI) directions (P < .0001). We also observed a strong correlation of the external surrogate anterior-posterior motion to the tumor dominant SI motion (P < .0001). In the validation cohort, the internal fiducial SI motion was the only reliable predictor of lung tumor motion. Conclusions The internal fiducials appear to be more reliable predictors of lung tumor motion than the external surrogate. The suitability of such airway-implanted internal fiducial markers for advanced motion management techniques should be further investigated. Although the external surrogate seems to be less reliable, its wide availability and noninvasive application support

PurposeStereotactic body radiation therapy (SBRT) has become the standard of care for inoperable early-stage non-small cell lung cancer and is often used for recurrent lung cancer and pulmonary metastases. Radiation-induced lung toxicity (RILT), including radiation pneumonitis and pulmonary fibrosis, is a major concern for which it is important to understand dosimetric and clinical predictors.Methods and materialsThis study was undertaken through the American Association of Physicists in Medicine's Working Group on Biological Effects of Stereotactic Body Radiotherapy. Data from studies of lung SBRT published through the summer of 2016 that provided detailed information about RILT were analyzed.ResultsNinety-seven studies were ultimately considered. Definitions of the risk organ and complication endpoints as well as dose-volume information presented varied among studies. The risk of RILT, including radiation pneumonitis and pulmonary fibrosis, was reported to be associated with the size and location of the tumor. Patients with interstitial lung disease appear to be especially susceptible to severe RILT. A variety of dosimetric parameters were reported to be associated with RILT. There was no apparent threshold "tolerance dose-volume" level. However, most studies noted safe treatment with a rate of symptomatic RILT of <10% to 15% after lung SBRT with a mean lung dose (MLD) of the combined lungs ≤8 Gy in 3 to 5 fractions and the percent of total lung volume receiving more than 20 Gy (V20) <10% to 15%.ConclusionsTo allow more rigorous analysis of this complication, future studies should standardize reporting by including standardized endpoint and volume definitions and providing dose-volume information for all patients, with and without RILT.

Accurate and robust segmentation of lung cancers from CT, even those located close to mediastinum, is needed to more accurately plan and deliver radiotherapy and to measure treatment response. Therefore, we developed a new cross-modality educed distillation (CMEDL) approach, using unpaired CT and MRI scans, whereby an informative teacher MRI network guides a student CT network to extract features that signal the difference between foreground and background. Our contribution eliminates two requirements of distillation methods: (i) paired image sets by using an image to image (I2I) translation and (ii) pre-training of the teacher network with a large training set by using concurrent training of all networks. Our framework uses an end-to-end trained unpaired I2I translation, teacher, and student segmentation networks. Architectural flexibility of our framework is demonstrated using 3 segmentation and 2 I2I networks. Networks were trained with 377 CT and 82 T2w MRI from different sets of patients, with independent validation (N=209 tumors) and testing (N=609 tumors) datasets. Network design, methods to combine MRI with CT information, distillation learning under informative (MRI to CT), weak (CT to MRI) and equal teacher (MRI to MRI), and ablation tests were performed. Accuracy was measured using Dice similarity (DSC), surface Dice (sDSC), and Hausdorff distance at the 95$^{th}$ percentile (HD95). The CMEDL approach was significantly (p $<$ 0.001) more accurate (DSC of 0.77 vs. 0.73) than non-CMEDL methods with an informative teacher for CT lung tumor, with a weak teacher (DSC of 0.84 vs. 0.81) for MRI lung tumor, and with equal teacher (DSC of 0.90 vs. 0.88) for MRI multi-organ segmentation. CMEDL also reduced inter-rater lung tumor segmentation variabilities.., Comment: This manuscript is has been accepted by IEEE Transactions on Medical Imaging

Despite the widespread availability of in-treatment room cone beam computed tomography (CBCT) imaging, due to the lack of reliable segmentation methods, CBCT is only used for gross set up corrections in lung radiotherapies. Accurate and reliable auto-segmentation tools could potentiate volumetric response assessment and geometry-guided adaptive radiation therapies. Therefore, we developed a new deep learning CBCT lung tumor segmentation method. Methods: The key idea of our approach called cross modality educed distillation (CMEDL) is to use magnetic resonance imaging (MRI) to guide a CBCT segmentation network training to extract more informative features during training. We accomplish this by training an end-to-end network comprised of unpaired domain adaptation (UDA) and cross-domain segmentation distillation networks (SDN) using unpaired CBCT and MRI datasets. Feature distillation regularizes the student network to extract CBCT features that match the statistical distribution of MRI features extracted by the teacher network and obtain better differentiation of tumor from background.} We also compared against an alternative framework that used UDA with MR segmentation network, whereby segmentation was done on the synthesized pseudo MRI representation. All networks were trained with 216 weekly CBCTs and 82 T2-weighted turbo spin echo MRI acquired from different patient cohorts. Validation was done on 20 weekly CBCTs from patients not used in training. Independent testing was done on 38 weekly CBCTs from patients not used in training or validation. Segmentation accuracy was measured using surface Dice similarity coefficient (SDSC) and Hausdroff distance at 95th percentile (HD95) metrics., Comment: The paper has been accepted to Medical Physics

This article addresses the process of locating global violence as a project of politicisation through the example of early Japanese-sponsored critiques of American racism. Forged in the First World War, anti-racist critiques carved out a new space for global political debate, consciously defying and counteracting conventional geographies of liberal international influence from the West to ‘the rest’. Offering an alternative to Atlantic critiques of Japanese social defects, critics mobilised by the Japanese Kokuryūkai took aim at racism as an essential defect of American society and worldviews. The article probes to what degree the exposure of violence triggered coalitions of critique between Japanese diagnosticians and African-American victims while simultaneously spurring the radical perception of Asian social life as ethically and spiritually superior to liberalism. As such, the publicity of anti-racism invites fresh avenues of transnational, less US-centric history to identify long-term repercussions of racism at the intersection of local social abuse and global politicisation.

BackgroundThe COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic.MethodsFor this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC.ResultsIn a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatme

BackgroundThe COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic.MethodsFor this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC.ResultsIn a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatme

This thesis seeks to answer the question: How has India and Pakistan’s nuclear strategy development changed the security environment in South Asia? By applying a constructivist approach to this problem, this thesis challenges the dominant neorealist discourse on nuclear deterrence. By researching the nuclear command-and-control structure of India and Pakistan, instead of nuclear doctrine, this thesis has produced the following conclusions. Pakistan’s nuclear posture continues to inhibit India’s ability to compel Pakistan, raising the risk of nuclear escalation. India and Pakistan are horizontally developing their nuclear forces, raising the cost of nuclear escalation. India and Pakistan’s nuclear command-and control measures are respectively trending more towards positive control, or are already positive control-oriented, increasing the risk of unwanted nuclear use. India and Pakistan are vertically developing their nuclear forces as well, expanding their capabilities to include tactical nuclear weapons and sea-based missiles, thus lowering the threshold for nuclear use. This thesis finds that the development of India and Pakistan’s nuclear posture has opened up new avenues for a crisis to escalate to the nuclear level, and increased the number of nuclear missiles that would be involved.

Surrounded by fragile and unstable states on all sides, the Central African Republic is located within a complex system of violence in which various conflicts feed and perpetuate each other. Facilitated by porous borders and tribal loyalties, regionalised conflicts have become an almost constant feature of life in the hinterlands of Sudan, South Sudan, the CAR and Chad. In focusing on the Seleka Rebellion of 2012, and locating it within this system of conflict, this thesis seeks to illustrate the cycles of violence such an arrangement helps to create. Building on this, the thesis will argue that the inability for the UN to locate the CAR within a conflict system and accommodate for this in their peacekeeping efforts, rendered the initial MINUSCA intervention of 2014 a misguided approach at bringing stability to the country. This thesis will argue that the UN must begin to address the structural issue which allow for cycles of violence to continue across the region. In order to do this, this thesis argues that, the statist discourse that pervaded the MINUSCA mandate must be replaced with a great appreciation for the lived reality of those in Central Africa, in particular by embracing tribal loyalties.

This thesis looks at the social movement that started a process of securitization concerning sexual violence in India. The gang rape and subsequent death of Jyoti Singh, in December 2012, are taken as the beginning of securitization because of the immense impact they had on Indian society; protests erupted around the country and these led to important legal changes. Who were the actors of securitization? What made the gang rape of Jyoti Singh such a source of protest and why did securitization not commence earlier? Has sexual violence in India been successfully securitized since 2012? What are the prospect for longer term securitization? Through looking at secondary literature, statistical information, interviews with people who experienced the securitization process on the ground and by analysing changes in legislation, this thesis seeks to answer these questions. Although India is a complex country with many different languages, religions and castes – all factors that make it hard for a securitization process to be successful – a securitization process (of sorts) began in 2012. The roles of a new middle-class and of social media were immense in transforming the 2012 protests into a powerful social movement. The concept of contentious politics proved important in the initiation of the securitization process, but to date it has been unable to reach the desired results. Increased criminalisation of politics, incorrect and incomplete implementation of several suggestions – made by legal scholars to the Indian government – and a faulty system of law and order mean that Indian society has not become safe for women yet. There is certainly hope for the future; the Indian government means to implement education reforms and here and there independent securitization measures are being taken by the Indian police.

BackgroundThe COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic.MethodsFor this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC.ResultsIn a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatme

BackgroundThe COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic.MethodsFor this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC.ResultsIn a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatme

This thesis seeks to answer the question: How has India and Pakistan’s nuclear strategy development changed the security environment in South Asia? By applying a constructivist approach to this problem, this thesis challenges the dominant neorealist discourse on nuclear deterrence. By researching the nuclear command-and-control structure of India and Pakistan, instead of nuclear doctrine, this thesis has produced the following conclusions. Pakistan’s nuclear posture continues to inhibit India’s ability to compel Pakistan, raising the risk of nuclear escalation. India and Pakistan are horizontally developing their nuclear forces, raising the cost of nuclear escalation. India and Pakistan’s nuclear command-and control measures are respectively trending more towards positive control, or are already positive control-oriented, increasing the risk of unwanted nuclear use. India and Pakistan are vertically developing their nuclear forces as well, expanding their capabilities to include tactical nuclear weapons and sea-based missiles, thus lowering the threshold for nuclear use. This thesis finds that the development of India and Pakistan’s nuclear posture has opened up new avenues for a crisis to escalate to the nuclear level, and increased the number of nuclear missiles that would be involved.

Surrounded by fragile and unstable states on all sides, the Central African Republic is located within a complex system of violence in which various conflicts feed and perpetuate each other. Facilitated by porous borders and tribal loyalties, regionalised conflicts have become an almost constant feature of life in the hinterlands of Sudan, South Sudan, the CAR and Chad. In focusing on the Seleka Rebellion of 2012, and locating it within this system of conflict, this thesis seeks to illustrate the cycles of violence such an arrangement helps to create. Building on this, the thesis will argue that the inability for the UN to locate the CAR within a conflict system and accommodate for this in their peacekeeping efforts, rendered the initial MINUSCA intervention of 2014 a misguided approach at bringing stability to the country. This thesis will argue that the UN must begin to address the structural issue which allow for cycles of violence to continue across the region. In order to do this, this thesis argues that, the statist discourse that pervaded the MINUSCA mandate must be replaced with a great appreciation for the lived reality of those in Central Africa, in particular by embracing tribal loyalties.

This thesis looks at the social movement that started a process of securitization concerning sexual violence in India. The gang rape and subsequent death of Jyoti Singh, in December 2012, are taken as the beginning of securitization because of the immense impact they had on Indian society; protests erupted around the country and these led to important legal changes. Who were the actors of securitization? What made the gang rape of Jyoti Singh such a source of protest and why did securitization not commence earlier? Has sexual violence in India been successfully securitized since 2012? What are the prospect for longer term securitization? Through looking at secondary literature, statistical information, interviews with people who experienced the securitization process on the ground and by analysing changes in legislation, this thesis seeks to answer these questions. Although India is a complex country with many different languages, religions and castes – all factors that make it hard for a securitization process to be successful – a securitization process (of sorts) began in 2012. The roles of a new middle-class and of social media were immense in transforming the 2012 protests into a powerful social movement. The concept of contentious politics proved important in the initiation of the securitization process, but to date it has been unable to reach the desired results. Increased criminalisation of politics, incorrect and incomplete implementation of several suggestions – made by legal scholars to the Indian government – and a faulty system of law and order mean that Indian society has not become safe for women yet. There is certainly hope for the future; the Indian government means to implement education reforms and here and there independent securitization measures are being taken by the Indian police.

We developed a new joint probabilistic segmentation and image distribution matching generative adversarial network (PSIGAN) for unsupervised domain adaptation (UDA) and multi-organ segmentation from magnetic resonance (MRI) images. Our UDA approach models the co-dependency between images and their segmentation as a joint probability distribution using a new structure discriminator. The structure discriminator computes structure of interest focused adversarial loss by combining the generated pseudo MRI with probabilistic segmentations produced by a simultaneously trained segmentation sub-network. The segmentation sub-network is trained using the pseudo MRI produced by the generator sub-network. This leads to a cyclical optimization of both the generator and segmentation sub-networks that are jointly trained as part of an end-to-end network. Extensive experiments and comparisons against multiple state-of-the-art methods were done on four different MRI sequences totalling 257 scans for generating multi-organ and tumor segmentation. The experiments included, (a) 20 T1-weighted (T1w) in-phase mdixon and (b) 20 T2-weighted (T2w) abdominal MRI for segmenting liver, spleen, left and right kidneys, (c) 162 T2-weighted fat suppressed head and neck MRI (T2wFS) for parotid gland segmentation, and (d) 75 T2w MRI for lung tumor segmentation. Our method achieved an overall average DSC of 0.87 on T1w and 0.90 on T2w for the abdominal organs, 0.82 on T2wFS for the parotid glands, and 0.77 on T2w MRI for lung tumors., Comment: This paper has been accepted by IEEE Transactions on Medical Imaging

We implemented and evaluated a multiple resolution residual network (MRRN) for multiple normal organs-at-risk (OAR) segmentation from computed tomography (CT) images for thoracic radiotherapy treatment (RT) planning. Our approach simultaneously combines feature streams computed at multiple image resolutions and feature levels through residual connections. The feature streams at each level are updated as the images are passed through various feature levels. We trained our approach using 206 thoracic CT scans of lung cancer patients with 35 scans held out for validation to segment the left and right lungs, heart, esophagus, and spinal cord. This approach was tested on 60 CT scans from the open-source AAPM Thoracic Auto-Segmentation Challenge dataset. Performance was measured using the Dice Similarity Coefficient (DSC). Our approach outperformed the best-performing method in the grand challenge for hard-to-segment structures like the esophagus and achieved comparable results for all other structures. Median DSC using our method was 0.97 (interquartile range [IQR]: 0.97-0.98) for the left and right lungs, 0.93 (IQR: 0.93-0.95) for the heart, 0.78 (IQR: 0.76-0.80) for the esophagus, and 0.88 (IQR: 0.86-0.89) for the spinal cord., Comment: MIDL 2020 short paper

The Kazakh language is currently undergoing a dramatic transformation after the 2017 announcement of a switch from Cyrillic to Latin characters. Furthermore, President Nursultan Nazarbayev effectively banned the Russian language from his cabinet in March 2018. Yet in Kazakhstan, only around 65% of the population speaks and understands Kazakh, while upwards of 90% use Russian as their primary language of communication, including the European Slavic population (Russians, Ukrainians and Byelorussians) which constitutes over one quarter of the whole. These moves could put the Russian-speaking population of Kazakhstan at a disadvantage. At a time when the Kremlin is become more assertive in its region and protective of ethnic Russians living abroad, this could have foreign political consequences for Astana. With this observation as its starting point, this thesis will explore the domestic and international dimensions of recent Kazakh language policy to come to an understanding as to why the policy was carried out. In doing so, it will also provide an up-to-date study of Kazakhstan’s multi-vector foreign policy. It will be shown that three factors provided the main impetus for the policy: economic modernisation, in which the English language plays an ever greater role; the need for a stronger sense of national identity, in which links to other Turkic-speaking countries have become more important; and a greater distancing from Moscow, which involves removing the last few links to the Soviet Union.

With a rule-based international order less obvious than before, this thesis aims to analyse the likelihood of a stable alliance between the European Union and China. This thesis looks into the development of Special Economic Zones as a driver of Chinese economic growth since its opening-up and reform in 1979. Additionally, it looks at how the relationship between the EU and China has developed during that time. Furthermore, it delves into how the EU was connected with non-Chinese SEZs and draws up similarities and differences with Chinese SEZs. An outline of the recent Belt and Road Initiative will be given, which is relevant as China has placed SEZs within this initiative. Four theoretical concepts will be evaluated to determine the most appropriate theory for encompassing China’s global rise, political and economic clout, its regional outreach and the export of SEZs as part of the BRI. Ultimately, the EU must review and engage with SEZs within the BRI with more scrutiny. The role China plays in the international order will increase due to its expanding position as a regional hegemon which is enabled by the growth potential of the BRI and specifically by using SEZs as an export product, which in turn allows for domestic economic growth to continue, and domestic stability ensures.

Barring a brief period of postcolonial amity in the 1950s, the Sino-Indian relationship has largely been characterised by mutual suspicion and conflict. Diplomatic relations remained thin and economic interactions negligible. However since 2003, Beijing and New Delhi have forged a substantive trading relationship generating considerable optimism about resolving past disputes. Today, despite maintaining one of the largest ‘South-South’ trade relationships in the world, considerable asymmetries in bilateral trade have been exposed, adding a new source of friction to a long list of unresolved historical disputes. This thesis explores how growing Sino-Indian economic interdependence has shaped the past two decades of rapprochement. Using trade expectations theory and a systematic analysis of contemporary Indian political discourse, I demonstrate how the positive expectations of future trade that initially supported Sino-Indian rapprochement have now faded. This has manifested in increased bilateral tension over the past five years, in particular over Beijing’s Belt Road Initiative, a dynamic that appears to conform to Copeland’s trade-security dilemma.

The Kazakh language is currently undergoing a dramatic transformation after the 2017 announcement of a switch from Cyrillic to Latin characters. Furthermore, President Nursultan Nazarbayev effectively banned the Russian language from his cabinet in March 2018. Yet in Kazakhstan, only around 65% of the population speaks and understands Kazakh, while upwards of 90% use Russian as their primary language of communication, including the European Slavic population (Russians, Ukrainians and Byelorussians) which constitutes over one quarter of the whole. These moves could put the Russian-speaking population of Kazakhstan at a disadvantage. At a time when the Kremlin is become more assertive in its region and protective of ethnic Russians living abroad, this could have foreign political consequences for Astana. With this observation as its starting point, this thesis will explore the domestic and international dimensions of recent Kazakh language policy to come to an understanding as to why the policy was carried out. In doing so, it will also provide an up-to-date study of Kazakhstan’s multi-vector foreign policy. It will be shown that three factors provided the main impetus for the policy: economic modernisation, in which the English language plays an ever greater role; the need for a stronger sense of national identity, in which links to other Turkic-speaking countries have become more important; and a greater distancing from Moscow, which involves removing the last few links to the Soviet Union.

Tumor cure with conventional fractionated radiotherapy is 65%, dependent on tumor cell-autonomous gradual buildup of DNA double-strand break (DSB) misrepair. Here we report that single-dose radiotherapy (SDRT), a disruptive technique that ablates more than 90% of human cancers, operates a distinct dual-target mechanism, linking acid sphingomyelinase-mediated (ASMase-mediated) microvascular perfusion defects to DNA unrepair in tumor cells to confer tumor cell lethality. ASMase-mediated microcirculatory vasoconstriction after SDRT conferred an ischemic stress response within parenchymal tumor cells, with ROS triggering the evolutionarily conserved SUMO stress response, specifically depleting chromatin-associated free SUMO3. Whereas SUMO3, but not SUMO2, was indispensable for homology-directed repair (HDR) of DSBs, HDR loss of function after SDRT yielded DSB unrepair, chromosomal aberrations, and tumor clonogen demise. Vasoconstriction blockade with the endothelin-1 inhibitor BQ-123, or ROS scavenging after SDRT using peroxiredoxin-6 overexpression or the SOD mimetic tempol, prevented chromatin SUMO3 depletion, HDR loss of function, and SDRT tumor ablation. We also provide evidence of mouse-to-human translation of this biology in a randomized clinical trial, showing that 24 Gy SDRT, but not 3×9 Gy fractionation, coupled early tumor ischemia/reperfusion to human cancer ablation. The SDRT biology provides opportunities for mechanism-based selective tumor radiosensitization via accessing of SDRT/ASMase signaling, as current studies indicate that this pathway is tractable to pharmacologic intervention.

With a rule-based international order less obvious than before, this thesis aims to analyse the likelihood of a stable alliance between the European Union and China. This thesis looks into the development of Special Economic Zones as a driver of Chinese economic growth since its opening-up and reform in 1979. Additionally, it looks at how the relationship between the EU and China has developed during that time. Furthermore, it delves into how the EU was connected with non-Chinese SEZs and draws up similarities and differences with Chinese SEZs. An outline of the recent Belt and Road Initiative will be given, which is relevant as China has placed SEZs within this initiative. Four theoretical concepts will be evaluated to determine the most appropriate theory for encompassing China’s global rise, political and economic clout, its regional outreach and the export of SEZs as part of the BRI. Ultimately, the EU must review and engage with SEZs within the BRI with more scrutiny. The role China plays in the international order will increase due to its expanding position as a regional hegemon which is enabled by the growth potential of the BRI and specifically by using SEZs as an export product, which in turn allows for domestic economic growth to continue, and domestic stability ensures.

Barring a brief period of postcolonial amity in the 1950s, the Sino-Indian relationship has largely been characterised by mutual suspicion and conflict. Diplomatic relations remained thin and economic interactions negligible. However since 2003, Beijing and New Delhi have forged a substantive trading relationship generating considerable optimism about resolving past disputes. Today, despite maintaining one of the largest ‘South-South’ trade relationships in the world, considerable asymmetries in bilateral trade have been exposed, adding a new source of friction to a long list of unresolved historical disputes. This thesis explores how growing Sino-Indian economic interdependence has shaped the past two decades of rapprochement. Using trade expectations theory and a systematic analysis of contemporary Indian political discourse, I demonstrate how the positive expectations of future trade that initially supported Sino-Indian rapprochement have now faded. This has manifested in increased bilateral tension over the past five years, in particular over Beijing’s Belt Road Initiative, a dynamic that appears to conform to Copeland’s trade-security dilemma.

The Kazakh language is currently undergoing a dramatic transformation after the 2017 announcement of a switch from Cyrillic to Latin characters. Furthermore, President Nursultan Nazarbayev effectively banned the Russian language from his cabinet in March 2018. Yet in Kazakhstan, only around 65% of the population speaks and understands Kazakh, while upwards of 90% use Russian as their primary language of communication, including the European Slavic population (Russians, Ukrainians and Byelorussians) which constitutes over one quarter of the whole. These moves could put the Russian-speaking population of Kazakhstan at a disadvantage. At a time when the Kremlin is become more assertive in its region and protective of ethnic Russians living abroad, this could have foreign political consequences for Astana. With this observation as its starting point, this thesis will explore the domestic and international dimensions of recent Kazakh language policy to come to an understanding as to why the policy was carried out. In doing so, it will also provide an up-to-date study of Kazakhstan’s multi-vector foreign policy. It will be shown that three factors provided the main impetus for the policy: economic modernisation, in which the English language plays an ever greater role; the need for a stronger sense of national identity, in which links to other Turkic-speaking countries have become more important; and a greater distancing from Moscow, which involves removing the last few links to the Soviet Union.

Lung tumors, especially those located close to or surrounded by soft tissues like the mediastinum, are difficult to segment due to the low soft tissue contrast on computed tomography images. Magnetic resonance images contain superior soft-tissue contrast information that can be leveraged if both modalities were available for training. Therefore, we developed a cross-modality educed learning approach where MR information that is educed from CT is used to hallucinate MRI and improve CT segmentation. Our approach, called cross-modality educed deep learning segmentation (CMEDL) combines CT and pseudo MR produced from CT by aligning their features to obtain segmentation on CT. Features computed in the last two layers of parallelly trained CT and MR segmentation networks are aligned. We implemented this approach on U-net and dense fully convolutional networks (dense-FCN). Our networks were trained on unrelated cohorts from open-source the Cancer Imaging Archive CT images (N=377), an internal archive T2-weighted MR (N=81), and evaluated using separate validation (N=304) and testing (N=333) CT-delineated tumors. Our approach using both networks were significantly more accurate (U-net $P <0.001$; denseFCN $P <0.001$) than CT-only networks and achieved an accuracy (Dice similarity coefficient) of 0.71$\pm$0.15 (U-net), 0.74$\pm$0.12 (denseFCN) on validation and 0.72$\pm$0.14 (U-net), 0.73$\pm$0.12 (denseFCN) on the testing sets. Our novel approach demonstrated that educing cross-modality information through learned priors enhances CT segmentation performance, Comment: This paper has been accepted by MICCAI 2019

Lack of large expert annotated MR datasets makes training deep learning models difficult. Therefore, a cross-modality (MR-CT) deep learning segmentation approach that augments training data using pseudo MR images produced by transforming expert-segmented CT images was developed. Eighty-One T2-weighted MRI scans from 28 patients with non-small cell lung cancers were analyzed. Cross-modality prior encoding the transformation of CT to pseudo MR images resembling T2w MRI was learned as a generative adversarial deep learning model. This model augmented training data arising from 6 expert-segmented T2w MR patient scans with 377 pseudo MRI from non-small cell lung cancer CT patient scans with obtained from the Cancer Imaging Archive. A two-dimensional Unet implemented with batch normalization was trained to segment the tumors from T2w MRI. This method was benchmarked against (a) standard data augmentation and two state-of-the art cross-modality pseudo MR-based augmentation and (b) two segmentation networks. Segmentation accuracy was computed using Dice similarity coefficient (DSC), Hausdroff distance metrics, and volume ratio. The proposed approach produced the lowest statistical variability in the intensity distribution between pseudo and T2w MR images measured as Kullback-Leibler divergence of 0.069. This method produced the highest segmentation accuracy with a DSC of 0.75 and the lowest Hausdroff distance on the test dataset. This approach produced highly similar estimations of tumor growth as an expert (P = 0.37). A novel deep learning MR segmentation was developed that overcomes the limitation of learning robust models from small datasets by leveraging learned cross-modality priors to augment training. The results show the feasibility of the approach and the corresponding improvement over the state-of-the-art methods., Comment: Submitted to Medical Physics

This thesis explores the relationship between the policymakers of the US-Japan security alliance and feminist anti-base protestors in Okinawa. In particular, it considers how a particularly violent rape, committed by three US personnel in 1995, sparked a wave of anti-base protest that was predominantly led by women’s groups. The interaction between protestors and policymakers in the weeks and months afterwards created a crisis in Okinawa that threatened the entire US-Japan alliance, and led to significant changes being implemented in the US base network in Okinawa. Despite these changes, the situation in Okinawa remained tense. This highlights the issue at the centre of the crisis, that the two sides did not share any common ground in their understandings of the cause of the rape or potential solutions. Subsequent rapes, committed in 2000, 2001, 2002, 2003, 2008, 2012 and 2016, demonstrated to anti-base protestors that alliance policymakers had not addressed the fundamental problems with the US bases in Okinawa, while increasingly radical demands from protestors asked more than policymakers were willing to concede to. This thesis will therefore explore two key moments in this ongoing crisis, as well as two of the primary reasons why a lack of common ground continues to exist, in order to ascertain why a solution has remained elusive, and whether the actions of either side have had a bearing on the behaviour of the other.

The sudden expansion of ISIS over the past ten years has been a challenging topic for numerous experts on the field of international relations, who have sought to explain this rise of the jihadist ideology. And while there has been enough focus into analyzing the attacks and goals of the Islamic State in order for governments to implement counter strategies, the past four years have shifted the discussion into other aspects of the ISIS case. One topic of debate revolves around the explanation of how Islamic radicalization takes place within the Muslim youth of Europe. This thesis will make the case for linking Islamic radicalization with the effects of existential anxiety and identity insecurity within French prisons. Through constant interactions in society due to cultural globalization and which are enhanced by sentiments of isolation that the prison environment brings in, the thesis will analyze these connections with how the jihadist identity is promoted. By presenting Jihadism as the solution from this ‘identity crisis’, ISIS can radicalize and attain more followers. Lately this has been taking place within the isolated environment of French prisons. But why are French prisons so crucial for Islamic radicalization and why do they differ from the radicalization cases of young Muslims within the French society? These questions will be answered throughout the course of the thesis, finally linking the prisons to the historical perspective attributed to the creation of ISIS in order explain how identity formation can be linked so closely with the rise of extremist ideals. Finally the thesis will try to outline how this Islamic radicalization case on a domestic level of a prison can actually have consequences on an international scale.

UK arms exports to Saudi Arabia for use in the current conflict in Yemen, ongoing since March 2015, provides the focus for exploring the competing interests in the historic UK-Saudi relationship. Specific attention is given to the efforts of non-state actors to raise with the British government the issue of International Humanitarian Law (IHL) violations by Saudi Arabia and thus to compel it to halt licenses. The thesis demonstrates how the efforts of non-state actors have been unsuccessful in forcing the government to halt weapons sales to Saudi Arabia, despite the credible and authoritative evidence provided by them. Structured within Constructivist Theory and its implications for a state’s adherence to IHL, the thesis demonstrates Constructivism’s limitations in explaining a state’s compliance with IHL. Instead, the British Government has embarked upon a deliberate strategy of avoidance and manipulation of its supposed “robust” export regime, allowing it to continue to exploit the other competing interests in the UK-Saudi relationship. These interests are shown to be historically deep and complex, with financial and security factors playing the primary role in shaping its direction since the creation of the modern Saudi state in 1932.

Aside from a short period in the 1950s, China has been developing its space program indigenously up to the 1980s. Largely managed by the PLA, the expensive program required justification on the grounds of prestige and military benefits. With the normalisation of Sino-US relations in 1979, science and technology cooperation as well as commercial engagement with the US on space became an option for China. Under Deng’s leadership in the 1980s, the economic rationale for the space program gained in importance and satellite launch agreements were signed. Meanwhile, the prestige generated by the accomplishments in space continued to be used as demonstration of the CCPs economic success. In 1989, US international outrage at the Tiananmen square incident caused economic sanctions that also hit the Chinese space sector. The real blow to Sino-US engagement in space came in 1999 with the publication of the Cox report on US export policy regarding China. This report greatly exaggerated flaws in the policy and the threat China posed at the time. Afterwards, an era in which China threat theory dictated Congress’ decision-making on China and space took off. By tying human rights and democratisation to the issue of space cooperation, a handful of US Congressmen have been able to stifle Sino-US space engagement. These policies combine to form the US exclusionist policy towards the Chinese space program, which is fragmented, not based on strategy and of limited effectiveness. How damaging this will be to US leadership in space is still to be seen.

Aside from a short period in the 1950s, China has been developing its space program indigenously up to the 1980s. Largely managed by the PLA, the expensive program required justification on the grounds of prestige and military benefits. With the normalisation of Sino-US relations in 1979, science and technology cooperation as well as commercial engagement with the US on space became an option for China. Under Deng’s leadership in the 1980s, the economic rationale for the space program gained in importance and satellite launch agreements were signed. Meanwhile, the prestige generated by the accomplishments in space continued to be used as demonstration of the CCPs economic success. In 1989, US international outrage at the Tiananmen square incident caused economic sanctions that also hit the Chinese space sector. The real blow to Sino-US engagement in space came in 1999 with the publication of the Cox report on US export policy regarding China. This report greatly exaggerated flaws in the policy and the threat China posed at the time. Afterwards, an era in which China threat theory dictated Congress’ decision-making on China and space took off. By tying human rights and democratisation to the issue of space cooperation, a handful of US Congressmen have been able to stifle Sino-US space engagement. These policies combine to form the US exclusionist policy towards the Chinese space program, which is fragmented, not based on strategy and of limited effectiveness. How damaging this will be to US leadership in space is still to be seen.

This thesis explores the relationship between the policymakers of the US-Japan security alliance and feminist anti-base protestors in Okinawa. In particular, it considers how a particularly violent rape, committed by three US personnel in 1995, sparked a wave of anti-base protest that was predominantly led by women’s groups. The interaction between protestors and policymakers in the weeks and months afterwards created a crisis in Okinawa that threatened the entire US-Japan alliance, and led to significant changes being implemented in the US base network in Okinawa. Despite these changes, the situation in Okinawa remained tense. This highlights the issue at the centre of the crisis, that the two sides did not share any common ground in their understandings of the cause of the rape or potential solutions. Subsequent rapes, committed in 2000, 2001, 2002, 2003, 2008, 2012 and 2016, demonstrated to anti-base protestors that alliance policymakers had not addressed the fundamental problems with the US bases in Okinawa, while increasingly radical demands from protestors asked more than policymakers were willing to concede to. This thesis will therefore explore two key moments in this ongoing crisis, as well as two of the primary reasons why a lack of common ground continues to exist, in order to ascertain why a solution has remained elusive, and whether the actions of either side have had a bearing on the behaviour of the other.

The sudden expansion of ISIS over the past ten years has been a challenging topic for numerous experts on the field of international relations, who have sought to explain this rise of the jihadist ideology. And while there has been enough focus into analyzing the attacks and goals of the Islamic State in order for governments to implement counter strategies, the past four years have shifted the discussion into other aspects of the ISIS case. One topic of debate revolves around the explanation of how Islamic radicalization takes place within the Muslim youth of Europe. This thesis will make the case for linking Islamic radicalization with the effects of existential anxiety and identity insecurity within French prisons. Through constant interactions in society due to cultural globalization and which are enhanced by sentiments of isolation that the prison environment brings in, the thesis will analyze these connections with how the jihadist identity is promoted. By presenting Jihadism as the solution from this ‘identity crisis’, ISIS can radicalize and attain more followers. Lately this has been taking place within the isolated environment of French prisons. But why are French prisons so crucial for Islamic radicalization and why do they differ from the radicalization cases of young Muslims within the French society? These questions will be answered throughout the course of the thesis, finally linking the prisons to the historical perspective attributed to the creation of ISIS in order explain how identity formation can be linked so closely with the rise of extremist ideals. Finally the thesis will try to outline how this Islamic radicalization case on a domestic level of a prison can actually have consequences on an international scale.

UK arms exports to Saudi Arabia for use in the current conflict in Yemen, ongoing since March 2015, provides the focus for exploring the competing interests in the historic UK-Saudi relationship. Specific attention is given to the efforts of non-state actors to raise with the British government the issue of International Humanitarian Law (IHL) violations by Saudi Arabia and thus to compel it to halt licenses. The thesis demonstrates how the efforts of non-state actors have been unsuccessful in forcing the government to halt weapons sales to Saudi Arabia, despite the credible and authoritative evidence provided by them. Structured within Constructivist Theory and its implications for a state’s adherence to IHL, the thesis demonstrates Constructivism’s limitations in explaining a state’s compliance with IHL. Instead, the British Government has embarked upon a deliberate strategy of avoidance and manipulation of its supposed “robust” export regime, allowing it to continue to exploit the other competing interests in the UK-Saudi relationship. These interests are shown to be historically deep and complex, with financial and security factors playing the primary role in shaping its direction since the creation of the modern Saudi state in 1932.

The aim of this thesis was to examine the ways in which librarianswork to stimulate the joy of reading in boys. Four children- andschool librarians were chosen for interviews in which they wereasked questions about boys' reading and the approaches they usedto help boys. The librarians were asked if they perceived boys'reading as problematic, what methods they used to stimulate thejoy of reading and if they thought it would be helpful to work withboys and girls in different ways. They were asked what theythought was the biggest challenges in changing the boys’ attitudestowards reading and what they would do if they could choosefreely without any constraints in time or money.Aidan Chambers' "The circle of reading" was used to compare atheory about reading to the ways in wich the librarians worked andtheir thoughts about how to initiate reading. All the librariansshowed awareness about the situation with boys' decreasingreading abilities and they had all developed approaches to helpstimulate boys’ reading in slightly different ways. Theirapproaches included carefully planned media acquisition and booktalks as well as displaying the books according to different themessuch as genres and organising special book shelves for popularbook series., Program: Bibliotekarie

The aim of this thesis was to examine the ways in which librarianswork to stimulate the joy of reading in boys. Four children- andschool librarians were chosen for interviews in which they wereasked questions about boys' reading and the approaches they usedto help boys. The librarians were asked if they perceived boys'reading as problematic, what methods they used to stimulate thejoy of reading and if they thought it would be helpful to work withboys and girls in different ways. They were asked what theythought was the biggest challenges in changing the boys’ attitudestowards reading and what they would do if they could choosefreely without any constraints in time or money.Aidan Chambers' "The circle of reading" was used to compare atheory about reading to the ways in wich the librarians worked andtheir thoughts about how to initiate reading. All the librariansshowed awareness about the situation with boys' decreasingreading abilities and they had all developed approaches to helpstimulate boys’ reading in slightly different ways. Theirapproaches included carefully planned media acquisition and booktalks as well as displaying the books according to different themessuch as genres and organising special book shelves for popularbook series., Program: Bibliotekarie