Contexte ─ L’incidence, les caractéristiques, et le pronostic (vital et fonctionnel) de la mort subite du sportif n’ont pas été étudiés en population générale. Méthodes ─ Etude observationnelle prospective menée par l’Institut National de la Santé et de la Recherche Médicale en collaboration avec le Service d’Aide Médicale Urgente (SAMU) dans 60 départements français (2005–2010) incluant les sujets de 10 à 75 ans présentant une mort subite (récupérée ou non) au cours d’une activité sportive de loisir ou de compétition. La détection des cas a été assurée par deux sources indépendantes. L’information a été recueillie selon le modèle d’Utstein. Les incidences ont été calculées par million d’habitants et million de participants sportifs, en considérant les 20ème et 80ème percentiles des départements les plus participants. Des analyses complémentaires ont été menées chez les femmes et pour les sports les plus en cause. Compte tenu de disparités régionales importantes en termes de survie, la distribution des facteurs (individuels et communautaires) classiquement associés à la survie (à la sortie de l’hôpital) a été examinée dans 4 groupes de survie (<10%, 10–20, 20–40, et >40%). L’analyse des facteurs associés à la survie a été effectuée par régression logistique.Résultats ─ Au total, 820 cas ont été collectés, et l’incidence totale a été évaluée entre 5 et 17 cas par million d’habitants par an en France. Seulement 6% des cas sont survenus chez le jeune athlète de compétition. Après considération des taux de participation sportive, l’incidence chez l’homme a été estimée entre 11,2 (95% IC 10,4–12,1) et 33,8 (95% IC 30,9–36,8) cas par million de participants et par an, l’incidence chez la femme étant, en comparaison avec l’homme, extrêmement faible, en particulier chez les 40–54 ans avec un risque relatif de 0,03 (95% IC 0,01–0,07). L’incidence augmentait significativement avec l’âge chez l’homme (risque relatif 2,51, 95 % IC 2,10–3,01, quand âge >35 ans), et était plus importante dans certains sports (cyclisme vs. natation, p<0,0001). L’âge moyen des sujets était de 46±15 ans. Des antécédents cardiovasculaires étaient rapportés dans 12% des cas. Le taux de survie moyen à la sortie de l’hôpital était de 15,7% (95% IC 13,2–18,2), avec cependant des disparités départementales majeures (de 0 à 47%), alors que le pronostic neurologique restait favorable chez 80% des survivants. La description en 4 groupes de survie a démontré l’absence de différence significative en termes de caractéristiques des sujets, de circonstances de survenue, de délai de prise en charge, et de mortalité intra-hospitalière. A l’inverse, des différences majeures ont été observées concernant l’initiation du massage cardiaque par le témoin (15% à 81%, p<0,001), le rythme initialement choquable (29% à 79%, p<0,001), le niveau de formation de la population aux premiers secours (p<0,001) et la densité de défibrillateurs extra-hospitaliers dans le département (p<0,001). Le défibrillateur n’a que rarement été utilisé par les témoins avant l’arrivée des premiers secours (<1%). Au final, les facteurs individuels suivants étaient indépendamment associés à la survie à la sortie de l’hôpital : massage cardiaque par témoin (OR 3,73, 95% IC 2,19–6,39, p<0,0001), délai d’intervention (OR 1,32, 95% IC 1,08–1,61, p=0,006), présence d’un rythme choquable initial (OR 3,71, 95% IC 2,07–6,64, p<0,0001). Après ajustement sur les facteurs pronostiques individuels, seul le niveau de formation de la population aux premiers secours restait associé de façon significative à la survie (OR 1,64, 95% IC 1,17–2,31, p=0,004).Conclusions et perspectives ─ La mort subite est un problème de santé publique faisant intervenir les pompiers, le SAMU, les réanimateurs, les cardiologues, les épidémiologistes. Sa prise en charge est nécessairement multidisciplinaire et les progrès viendront d’une action concertée de santé publique. Concernant la mort subite du sportif, nos conclusions sont que (...) / Background – Although such data are available for young competitive athletes, the prevalence, characteristics and outcome of sports-related sudden cardiac death have not previously been assessed in the general population.Methods – A prospective and comprehensive national survey was carried out throughout France by the French Institute of Health and Medical Research from 2005 to 2010, involving subjects aged 10–75 years. Case detection for sports-related sudden cardiac death, during competitive or leisure activities, including resuscitated cardiac arrest, was undertaken via emergency medical services (Service d’Aide Médicale Urgente, SAMU) reporting and web-based screening of media releases. Data were collected according to Utstein’s style. Incidence calculations were reported by million of inhabitants as well as million of sports participants. Specific analyses were also carried out among women and specific sports. After having documented major regional survival disparities, we identified to which extent conventional evidence-based individual factors, known to be associated to survival, were distributed among different groups of survival. Moreover, we assessed if functional outcome was variable among groups of survival. Factors associated with survival were analyzed using regression logistic model.Results – The overall burden of sports-related sudden cardiac death was estimated between 5 and 17 cases per million inhabitants per year. Only 6% of cases occurred among young competitive athletes, with a specific incidence calculated to 9.8 (95% CI 3.7–16.0) per million per year. After considering participation rates, incidence in men sport participants was estimated from 11.2 (95% CI 10.4–12.1) to 33.8 (95% CI 30.9–36.8) per million of participants per year, dramatically higher than women-related incidence, particularly in the 45–54 year range (relative risk 0.03, 95% CI 0.01 to 0.07). By contrast with women, the incidence of sports-related sudden cardiac death in men significantly increased over age categories (p<0.0001), and incidence rates were substantially higher in men aged >35 years than men aged 35 years or less (RR 2.51, 95% CI 2.10–3.01). The mean survival rate at hospital discharge was 15.7% (95% CI 13.2–18.2), with major regional disparities among districts (from 0 to 47%), with however a highly similar favorable neurological outcome (80%). No difference was observed regarding subjects’ characteristics and circumstances of occurrence (including presence of witnesses, delays of intervention and public use of automatic external defibrillators) across survival groups. By contrast, major differences were noted regarding bystander initiation of cardiopulmonary resuscitation (15% to 81%, p<0.001) and presence of initial shockable rhythm (29% to 79%, p<0.001). Public use of automatic external defibrillator was dramatically low (<1%). Independent factors for survival included bystander cardiopulmonary resuscitation (OR 3.73, 95% CI 2.19–6.39, p<0.0001), initial shockable rhythm (OR 3.71, 95% CI 2.07–6.64, p<0.0001) and short delay between cardiac arrest and resuscitation (OR 1.32, 95% CI 1.08–1.61, p=0.006). After adjustment on individual factors, only population education to Basic Life Support was significantly associated with survival (OR 1.64, 95% CI 1.17–2.31, p=0.004).Conclusions and perspectives – Sudden cardiac death is a public health issue, with the need for a multidisciplinary approach involving Emergency Cares, Cardiology, and Epidemiology. Regarding sports-related sudden death, our conclusions are the following (...)

This master thesis presents an approach on how to design moral behaviour in a scenario with een. een is an iteration of emobn which is based on bn, an action selection system with activation dynamics among modules, goal oriented and capable of prediction and planing. The design is based on current research from prominent psychologist like Haidt and uses Mikhial’s umg framework for causal and intentional validation. Also Roseman’s appraisal model and Haidt’s mft is used for determining moral emotions in a moral context. The design is tested against empirical results from philosophical experiment know as the trol- ley problem, a well known moral dilemma.

The goal of this study was to investigate the impact of physical, verbal and social bullying in high school on the adolescent’s sense of self, thereby improving the knowledge base and insight of counsellors who work with victims of bullying. The objectives of this study were: <ul><li>To build a knowledge base on the problem of bullying using existing literature. The knowledge base was used to form a holistic picture of the problem.</li> <li>To empirically investigate the impact that bullying in the school has on the adolescent’s sense of self.</li> <li>To provide conclusions and recommendations for teachers of school A as well as counsellors who, in the counselling setting, work with bullied children. </li></ul> This quantitative study endeavoured to answer the following research question: “What is the impact of bullying on the adolescent’s sense of self.” The researcher aimed to use the statistical analysis of the empirical study to improve the helping profession’s understanding of the phenomenon. This may lead to more successful intervention strategies on behalf of these adolescents. The study was feasible, as it was within the financial and practical means of the researcher. She had access to the school as she was employed there and obtained permission from the school, Department of Education, parents of participants, the participants themselves and The Ethical Committee of the University of Pretoria. The following themes emerged from the data analysis (when the male and female adolescents’ results were separated) namely: <ul><li>Physical bullying does not affect any parts of the sense of self of the female adolescent but does affect the physical and creative self of the male.</li> <li>Social bullying impacts every part of the female adolescent self but only affects the emotional, behavioural and creative sense of self of the male.</li> <li>Verbal bullying has an impact on every part of the female adolescents sense of self and affects all parts of the male sense of self except the physical and intellectual sense of self.</li></ul> From the research findings, recommendations were made on a micro, macro and exo- level. On a micro-level, this included improved intervention and prevention programmes in schools. On macro-level the researcher is of the opinion that the Department of Education of various districts need to ensure that policies are put in place as well as to support individual schools in their endeavours to stop bullying. On a meso-level, legislation changes and enforcement of the Bill of Human rights in schools are recommended. Copyright / Dissertation (MSD)--University of Pretoria, 2008. / Social Work and Criminology / unrestricted

Many virus infections induce a transient state of immune suppression in the infected host. Virus-induced T cell suppression can be caused by T cell activation-induced cell death (AICD), dendritic cell (DC) apoptosis, DC dysfunction, and/or the enhanced expression of immune-suppressive cytokines. It has been previously demonstrated that naïve bystander CD8 T cells derived from hosts experiencing an acute virus-specific T cell response underwent AICD when polyclonally activated by anti-CD3 in vitro (Zarozinski et al., 2000). Susceptibility of naïve bystander T cells to AICD could prevent the development of a new T cell response during an ongoing immune response, and thus render infected hosts immune suppressed. Although immune suppression could result in an enhanced susceptibility to superinfections, virus-infected individuals are more commonly resistant to superinfecting pathogens. Because of these seemingly contradictory conditions, we sought to investigate how acute viral infections impact naïve bystander CD8 T cells in vivo. More specifically, we asked whether bystander CD8 T cells are susceptible to immune suppression or whether they can contribute to the resistance to superinfections. In order to address this, we examined the responses of bystander CD8 T cells activated with cognate antigen during acute viral infections in vivo. We generated several in vivomodels using P14 (LCMV glycoprotein-specific), HY (male antigen-specific), and OT-I (ovalbumin-specific) transgenic CD8 T cells, which we defined as bystander during acute infections with lymphocytic choriomeningitis virus (LCMV), Pichinde virus (PV), vaccinia virus (VV), and murine cytomegalovirus (MCMV). Consistent with the enhanced susceptibility to cell death noted in vitro, we found that bystander CD8 T cells activated with cognate antigen in vivo during acute viral infections underwent markedly reduced proliferation. Virus-induced transient T cell suppression in vivo was not exclusively mediated by Fas-FasL- or TNF-induced AICD or due to an enhanced susceptibility to apoptosis. Instead, immune suppression in vivowas associated with a delayed onset of division, which we found not to be due to a defect in antigen presentation, but rather due to a T cell intrinsic defect. Despite the suppressed proliferation of TCR-stimulated bystander CD8 T cells in vivo, we found an enhancement of the effector functions exerted by bystander CD8 T cells activated during acute viral infections. During acute viral infections or after stimulation with type 1 IFN (IFN-αβ) inducers, some bystander CD8 T cells were sensitized to immediately exert effector functions such as IFN-γ production and degranulation upon stimulation with high affinity cognate antigen. Sensitization of naïve CD8 T cells required self-MHC I and indirect effects of IFN-αβ, while IL-12, IL-18, and IFN-γ were not individually required. IL-15 was not required for the rapid expression of IFN-γ, but was required for up-regulation of granzyme B (GrzB). P14 and OT-I CD8 T cells, which are capable of homeostatic proliferation, could be sensitized by poly(I:C), but HY CD8 T cells, which are poor at homeostatic proliferation, could not, suggesting that the requirement for MHC I may be to present low affinity cryptically cross-reactive self antigens. Sensitized naive CD8 T cells up-regulated the t-box transcription factor Eomesodermin (Eomes), which can regulate these rapid effector functions. In conclusion, we demonstrate in this thesis that acute viral infections impact naïve bystander CD8 T cells such that their response to cognate antigen is altered. Prior to cognate antigen engagement, bystander CD8 T cells up-regulated Eomes, CD122, and GrzB. Following cognate antigen engagement, bystander CD8 T cells rapidly degranulated and expressed the effector cytokine IFN-γ. The ability of bystander CD8 T cells to rapidly exert effector functions may contribute to the resistance of virus-infected individuals to superinfections. Despite these rapid effector functions, the proliferation of TCR-stimulated bystander CD8 T cells was markedly inhibited. This reduced proliferation was found not to be a defect in antigen presentation, but was a T cell intrinsic defect in initiating division. Thus, bystander CD8 T cells were also susceptible to virus-induced immune suppression. It is also likely that virus-specific CD8 T cells that are not activated until later in the response, so-called latecomer CD8 T cells, may also be susceptible to immune enhancement and suppression. Thus, latecomer CD8 T cells would be able to rapidly exert effector functions at the expense of proliferation. Taken together, we propose that during an immune response, due to spatial and temporal gradients of antigen and inflammation, it is likely that a combination of heterogeneous T cells with different signal strengths and sequences of exposure from cytokines and peptide-MHC constitute the total T cell response to pathogens.

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No description available.

<p>Microbeam radiation therapy (MRT) is an experimental radiotherapy concept that has been primarily developed for the treatment of malignant brain tumours. MRT uses high flux synchrotron x-rays delivered as an array of parallel microbeams in high doses of irradiation in fractions of seconds. The aims of this study were to 1) investigate the induction of bystander effects after normal and tumour-bearing rat brains were exposed to MRT and homogenous radiation; 2) validate a brain bystander proteome by detecting protein expression throughout immunohistochemistry: and 3) to investigate whether communication of bystander signals can be produced between animals.</p> <p>Healthy and tumour-bearing Wistar rats were exposed to 17.5, 35, 70 or 350 Gy of MRT or homogenous field of synchrotron radiation to the right brain hemisphere. To study the communication of bystander effects between animals, irradiated rats shared the same cage with non-irradiated rats over a period of 48 hours. After euthanasia of the animals, brains and bladders were dissected, and samples for immunohistochemistry and bystander clonogenic assays were set up.</p> <p>Clonogenic survival of the reporter HPVG cells showed that bystander effects occurred in both the non-irradiated hemisphere and bladder of normal and tumour-bearing rats, while the irradiated hemisphere showed the direct effects of radiation. Moreover, communication of bystander signals was confirmed in the non-irradiated rats.</p> <p>In conclusion, the results suggest that the MRT and homogenous radiation of unilateral normal and tumour-bearing rat brains produce bystander signals that affect the whole organism and that those signals also can be transmitted to non-irradiated animals.</p> / Master of Science (MSc)

<p>Ionizing radiation is without a doubt an invaluable tool in diagnostic imaging as well as radiation therapy. With the growing number of medical and occupational exposures, together with challenges against the LNT model, low dose exposures and non-targeted effects have been subject to intensive research. Additionally, with the advances in the field of radiation therapy and longer life expectancy after the treatment, the risks associated with second malignancies following radiation therapy for various cancers has received a tremendous amount of attention. On the other hand, nicotine, as the addictive component of tobacco has been known for its adverse health effects and its relation to various types of cancers, accounting for one in 10 adult deaths worldwide. Both nicotine and low doses of radiation are amongst the stressors that widely affect the public. Surprisingly, the interactions between low-dose effects and nicotine exposure have not received the proper scientific attention. Our group has been involved in investigation of the non-targeted effects of radiation with a variety of endpoints. Different natural compounds and signalling molecules have also been studied in our lab for their possible role or contribution to bystander signalling. This research involves the study of the impact of nicotine on radiation-induced bystander effects and also radioadaptive responses. Different concentrations of nicotine were used to study the kinetics of the drug as well as any detrimental or modifying effects when used together with radiation. It was shown that nicotine has a protective effect on survival of the cells in certain concentrations that follows a biphasic model. Similar bimodal behaviour was observed with bystander effect. No adaptation to a challenge dose of radiation occurred as a result of incubation with varying concentrations of nicotine, nor was such an effect shown with a priming dose of radiation. The results of the present study suggest that nicotine has a complicated effect on the cells which can vary significantly depending on the concentrations used and also the duration of exposure. nAChRs may have an important role in the response of the bystander cells when nicotine is involved as the results showed a shift in the response of the receptors to nicotine. This thesis is aimed to shed light on the impact of nicotine and initiate more detailed investigations on pathways through which these effects are mediated.</p> / Master of Science (MSc)

Text in Afrikaans / Selfmoord is 'n kontroversiele aangeleentheid wat beide omstanders en agterblywendes met onsekerheid vervul. 'n Belangrike rede hiervoor is dat dit 'n onnatuurlike afsterwe is wat teen baie mense se norme en waardes indruis. ldiografiese navorsing is onderneem om die belewenisse van agterblywende gesinslede te ondersoek aangesien hulle die eintlike slagoffers van 'n selfmoord is wat met 'n komplekse realiteit gelaat word. Die doel van die navorsing was om riglyne daar te stel vir die hantering en ondersteuning van hierdie mense. Vanuit 'n in-diepte literatuurstudie, het dit geblyk dat die grootste probleme waarmee agterblywendes gekonfronteer word, wentel random problematiese emosies, veroordeling deur omstanders en belewings van persoonlike onvermoe om te midde van intense rousmart selfaktualisering optimaal te volvoer. 'n Vraelys wat aspekte (socs dit uit die literatuurstudie geblyk het) inkorporeer, is opgestel en aan agterblywendes gegee om te beantwoord. Van die belangrikste elemente wat na vore gekom het, is dat intense verhoudingskomplikasies na 'n selfmoord figureer, dat agterblywendes 'n behoefte het om rouverwerking teen hul eie tempo te doen, dat agterblywendes verkies dat omstanders nie voortdurend die gebeure sal ontleed en soek na oorsake in die teenwoordigheid van agterblywendes nie en dat elke agterblywende persoon se roubelewing persoonlik en uniek is. 'n Hoofstuk is gewy aan 'n wye verskeidenheid terapeutiese tegnieke wat geimplementeer kan word tydens hulpverlening aan agterblywendes. Die studie beskryf ook 'n gevallestudie en die verloop van sestien individuele terapeutiese sessies. In die terapeutiese insette is daar hoofsaaklik gebruik gemaak van hipnoterapie as 'n vorm van ontspanningsterapie waartydens daar gelokus word op problematiese emosies en persepsies wat voortgesette kwalitatiewe selfaktualisering belemmer. In die studie word Opvoedkundige Sielkundige riglyne vir hulpverlening aan agterblywendes, wat benut kan word deur hulpverleners (soos sielkundiges, onderwysers en ander ondersteuningsisteme). verskaf. Die studie bevestig dat die agterblywendes as die werklike slagoffers na 'n selfmoord agtergelaat word, maar dat sinvolle intervensie hierdie persone in staat kan stel om ten spyte van die gebeure weer optimaal te selfaktualiseer. / Suicide is a controversial topic. It causes both bystanders and survivors to feel insecure. An important reason for this is that it is an unnatural death which directly opposes the norms and values of the majority of people. ldiografic research has been undertaken to closely examine the experiences of suicide survivors as they are the real victims who are left to cope with a complex reality after a suicide. The objective of this study was to provide guidelines to effectively manage and render assistance to survivors. From an in depth review of available literature it appeared that troubled emotions, being denounced by bystanders and the inability to proceed with continued qualitative self-actualization are some of the most important problems survivors have to cope with. A questionnaire, incorporating significant aspects reported in literature, was compiled and given to survivors to complete. From their responses certain facets seemed to be problematic. Among the more problematic aspects were complicated interpersonal relations, the basic need to grieve at their own pace, the preference that bystanders avoid analysing the suicide and possible contributing factors (especially in the presence of survivors) and the recognition that each survivor's grief is personal and unique. A chapter has been devoted to a wide range of therapeutic techniques that can be implemented to facilitate the support given to survivors. The study also describes a case study as well as the progression of sixteen individual therapy sessions. Therapeutic intervention was mainly based on hypnotherapy as a form of relaxation therapy during which the focus is placed on problematic emotions and perceptions which prevent continued qualitative self-actualization. Educational Psychological guidelines along which assistance can be rendered by psychologists, teachers as well as other support services are given. This study not only confirms that the survivors are the actual victims of a suicide, but also that it is possible to assist these people to achieve optimal self-actualization through meaningful intervention. / Psychology of Education / D. Ed. (Sielkundige Opvoedkunde)

The purpose of this study was to examine how ethnicity and gender of victim and perpetrator might influence students’ assessment of the severity of cyber-harassment in three different contexts. One hypothesis was that severity is mediated by indicators of power (blame, control balance and status-difference), which in turn are dependent on dimensions of ethnicity and gender. A semi-factorial survey was conducted among 365 students in five different high schools in Stockholm county. The students assessed three different vignettes, which described 1) harassment on a blog, 2) grieving in a first-person-shooter video game and 3) the uploading of a nude picture on Facebook. The effects of the dimensions on participants’ perception of the harassment and choice of action were analysed using linear- and logistic regression analysis, respectively. The results showed the following in each respective vignette: 1) Male bystanders were more prone to choose a passive action if the victim was female and the perpetrator male. 2) Men attributed less blame to female victims while women made no such difference. 3) The results indicate that women deemed the situation more severe if the victim was female. To conclude, the effects of the dimensions seem to vary depending on the different contexts.