The historical narrative and our understanding about the low dose effects of radiation on the immune system has changed drastically from the beginning of the 20th century to now. A paradigm shift from the DNA target hit model to the one that also considers non-targeted effects (NTE) has attracted a lot of interest recently. Investigations to delineate mechanisms of NTE in the biological tissue have been carried out by various research groups where radiation induced genomic instability (RIGI), bystander effect (RIBE) and abscopal effect (AE) are the effects with most evidence available. This thesis addresses the question of whether low dose ionizing radiation (LDIR) stimulates or suppresses the immune system and how NTEs contribute to this immune modulation by adopting a two-pronged approach where first a narrative review constituting the introduction and literature review was performed followed by a systematic review using PRISMA guidelines to synthesize existing LDIR literature. This was prompted by our recent discovery that UVA photons are emitted by the irradiated cells and that these photons can trigger bystander effects in unirradiated recipients of these photons. Given the well-known association between UV radiation and the immune response, where these biphotons may pose as bystander signals potentiating processes in deep tissues as a consequence of ionising radiation, it is timely to revisit the field with a fresh lens. After reviewing various pathways and immune components that contribute to the beneficial and adverse effects induced by LDIR, it was found that these modulations can occur by way of NTE. However, the exact mechanistic underpinnings are still unclear and the literature examining low to medium dose effects of ionising radiation on the immune system is complex and controversial. Early work was compromised by lack of good dosimetry while later work mainly focuses on the involvement of immune responses in radiotherapy which typically uses high dose radiation. There is a lack of research in the LDIR/NTE field focussing on immune responses although bone marrow stem cells and lineages were critical in the identification and characterisation of NTE. This may be in part, a result of the difficulty of isolating NTE in whole organisms which are essential for good immune response studies. Models involving inter organism transmission of NTE are a promising route to overcome these issues. It is concluded that the simple question of whether LDIR stimulates or suppress the immune system is not as simple as initially hypothesized. An attempt was made to analyze if LDIR shifts the balance to immune suppression or enhancement via systematic review but, due to too many differences in the experimental methods in the current radiation and immune studies, a cookie-cutter answer was not possible. However, this thesis did point out the areas of concern such as lack of standardised tools in the field of radiobiological experimental research and quality of methods used which requires urgent attention. / Thesis / Master of Science (MSc)

In today's schools bullies have the power to be more tenacious, more vicious, and meaner than ever. We are all beginning to understand that victims of bullying are at a greater risk for depression, suicide, and hurting others through violent acts. The purpose of this qualitative study was to investigate common threads of effective Bully-Free School Zone character education programs as perceived by administrators, teachers, and parents in five middle schools in Western North Carolina. Through this strategic inquiry, I attempted to determine if the views of administrators, teachers, and parents were consistent with published research on anti-bullying programs. Specifically, the study focused on views of administrators, teachers, and parents of middle school students in grades five through eight by examining perceptions of the impact of bullying on students' safety. Participants shared their concerns about barriers to discipline programs and how school personnel and parents can contribute to a safer and more productive environment. The study was conducted in five middle schools in Western North Carolina. All participants were interviewed and asked open-ended questions during a three-week period in the spring of 2004. The study supports the hypothesis that well disciplined and productive anti-bullying programs are not products of good luck or chance; they result from efforts made by caring administrators, teachers, parents, and students. All stakeholders should have an interest in changing behaviors that lead to aggressive and violent acts. Exerting extra efforts toward minimizing disruptions and providing safer schools requires a team effort in working toward a common goal that students enter the building each day excited, enthused, and looking forward to their school day.

This master thesis explores how sexual harassment is handled and managed in organisations and to what extent bystander intervention is known and seen as a potential prevention mechanism. Ten interviews have been conducted with HR managers and other leading department heads working in private organisations in Germany. The purpose of this thesis was to gather knowledge on how sexual harassment is perceived and dealt with in those organisations under consideration of the concept of organisational culture and its impact. Bystander intervention has been discussed as a potential prevention strategy. Leadership behaviour and dominating power relations have been uncovered as significant impact factors shaping organisational culture and enabling space for sexually harassing behaviour to happen. Based on the findings this thesis offers implications for transforming organisations towards becoming more gender equal in the future such as creating awareness and enabling spaces to talk about it openly and educating people on forms and harms of sexual harassment as well as possibilities to act as a bystander.

Previous research suggests that most incidents of bullying occur in school settings. However, teachers are not always aware of bullying incidences and often do not intervene. As bullying has negative long-term consequences for the bully, victim, and bystander, it is important to identify effective ways to reduce this problem. Responding to incidents of bullying at school, bibliotherapy is a cost effective way to support students and teach coping strategies. Numerous bully-themed books model a variety of strategies to deter bullying. Because of their busy schedule and limited opportunities to review books, teachers may need assistance in identifying books that promote recommended strategies to deter incidents of bullying. This research investigated teachers' perceptions of bystander strategies in four selected bully-themed children's picture books. Selected books contained bystander responses to bullying. Participants included two kindergarten and two first-grade female teachers. Teachers read the four selected books with their classes. Afterward, the four teachers participated in a focus group to discuss outlined research questions. Additionally, teachers reviewed the Anti-Defamation League's recommended bystander strategies and rated the effectiveness of these strategies in reducing bullying. To assist young children in identifying with and understanding the story's message, focus group discussion emphasized the importance of selecting books with a straightforward storyline. Teachers reported enjoying using bibliotherapy and appreciated the power of a story to encourage student discussion about bullying. They also suggested that selected books should contain story characters that model appropriate strategies to deter bullying. In regard to their young students, teachers rated two strategies as most effective in deterring bullying: (a) encouraging the bystander to go with the victim to tell an adult and (b) telling the bully to stop. Summarizing information from the focus group and based on teachers' responses to a short questionnaire, suggestions are made to assist kindergarten and first-grade teachers in selecting books on the topic of bullying and sharing these books with their classes.

This thesis demonstrates the relevance of bystander effect mechanisms after exposure to two Synchrotron modalities – Microbeam Radiation Therapy and Pencilbeam – that are currently at the preclinical stage but aim to treat brain tumours. We elucidate the relationship between the hyper-radiosensitivity phenomenon and radiation-induced bystander effects by studying the dose response of three glioma cell lines. The relevance of these low-dose effects for both Synchrotron modalities is because the tissue exposed to low valley-doses is predicted to be where hyper-radiosensitivity and bystander effects might be expected to predominate. In vivo experiments were conducted in the European Synchrotron radiation Facility in Grenoble, France and also in the University of Freiburg’s Hospital in Freiburg, Germany. Experiments conducted in vitro were performed at McMaster University. The most relevant results of this thesis revealed that the low-dose hyper-radiosensitivity phenomenon can coexist with radiation-induced bystander effects and evidence points towards bystander signalling mechanisms as the primary cause of cell killing during hyper-radiosensitivity. Bystander and abscopal effects can occur in rats and even in immune-compromised nude mice after exposure to Synchrotron Microbeam Radiation and Pencilbeam. Bystander effects can be communicated from irradiated rats to healthy unirradiated cage mate rats and the presence of a tumour modulates both the bystander and abscopal responses. The γ-H2AX biomarker can successfully be used for the detection of DNA damage in the brain of rodents after Synchrotron Radiation. In conclusion, this thesis considerably expands the understanding of the role of bystander effects in cells lines, tissues, and animals exposed to Synchrotron radiation. It is suggested that further exploration of the role of bystander effects and hyper-radiosensitivity during Synchrotron treatments could identify new targets leading to better tumour control. / Thesis / Doctor of Science (PhD)

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This master thesis explores how sexual harassment is handled and managed in organisations and to what extent bystander intervention is known and seen as a potential prevention mechanism. Ten interviews have been conducted with HR managers and other leading department heads working in private organisations in Germany. The purpose of this thesis was to gather knowledge on how sexual harassment is perceived and dealt with in those organisations under consideration of the concept of organisational culture and its impact. Bystander intervention has been discussed as a potential prevention strategy. Leadership behaviour and dominating power relations have been uncovered as significant impact factors shaping organisational culture and enabling space for sexually harassing behaviour to happen. Based on the findings this thesis offers implications for transforming organisations towards becoming more gender equal in the future such as creating awareness and enabling spaces to talk about it openly and educating people on forms and harms of sexual harassment as well as possibilities to act as a bystander.

<p>Several labs have previously demonstrated that humoral immune responses at one mucosal tissue can disseminate to other mucosal sites, giving rise to the theory of the common mucosal immune system (CMIS). Evidence that demonstrates a similar link between systemic immune responses and mucosal protection is lacking despite indications that both mucosal and systemic memory B cells share common circulatory pathways. The focus of this study is to determine the contribution of blood-borne B cells to mucosal immunity in humans, and how B cells trafficking through blood can be induced to traffic to mucosal tissues.</p> <p>To address these aims, I have performed several analyses of active and inactive peripheral blood memory B cell (MBC) populations in normal, healthy humans. Analysis of recently activated blood B cells confirmed the revealed that the majority of pre-plasma cells (PPC) in blood of healthy, normal humans secrete IgA, and that the majority of IgA- positive PPC secrete primarily polymeric IgA. A large fraction of blood PPC also express CCR10, and this population contains the highest fraction of IgA-expressing and pIgA-secreting PPC in blood. In contrast, most CCR10- PPC secrete IgG, although a small fraction secretes and stains positive for IgA, and analysis of α4β7expression by blood MBC revealed that CCR10 is more inclusive of IgA-switched and pIgA-secreting PPC in blood. The data presented in this study demonstrate that IgA+/CCR10+ PPC represent the mucosal subset of PPC in the blood of healthy humans, and can be investigated as representative of recent or ongoing mucosal immune responses.</p> <p><em>In vitro </em>polyclonal stimulation of blood MBC through CD40 was able to induce CCR10 expression by blood MBC treated with IL-21, IL-2, IL-10 with additions of other germinal center (GC) cytokines such as IL-5 and TGF-β enhancing CCR10 induction. Surprisingly, CCR10 expression by IgG MBC stimulated under these conditions was similar to that of IgA MBC, demonstrating that CCR10 expression is not limited to IgA- switched B cell clones. The results of this study demonstrate that CCR10 expression is inducible by many GC factors, and importantly, is not limited to IgA-switched B cells.</p> <p>Systemic immunization of healthy volunteers with tetanus toxoid/diphtheria vaccine induced a robust systemic IgG response, but also resulted in a post-immunization mobilization of IgA PPC in blood. These PPC were not specific for tetanus or diphtheria, and in several volunteers showed specificity for mucosal pathogens such as poliovirus (PV) and herpes simplex virus (HSV) glycoproteins. In addition, stimulation of anti-HSV IgG memory was also observed. Thus we have demonstrated that a systemic immune response is capable of inducing antibody relevant to mucosal immunity, possibly exposing a mechanism through which systemic and mucosal humoral immune responses are linked.</p> <p>The studies presented here demonstrate the presence of mucosal B cell memory in blood and thus provide new insight into ways to assess and manipulate mucosal immunity.</p> / Doctor of Philosophy (Medical Science)