Narzissmus in romantischen Beziehungen: Unterstützungsprozesse und die moderierende Rolle des Vertrauens

Narcissism is associated with inter- and intrapersonal dynamics that often lead to long-term difficulties, affecting the everyday lives of individuals with high levels of narcissism, as well as those of their interaction partners. Previous research on narcissism in romantic relationships has shown that these difficulties extend to intimate bonds, with individuals with high levels of narcissism and their partners generally facing greater challenges in maintaining satisfying and enduring relationships. This study examined grandiose and vulnerable narcissism within the framework of dyadic support processes (i.e. enacted and perceived negative dyadic coping), which are essential for maintaining healthy and functional relationships. Additionally, the moderating role of trust within these support processes was investigated. Data were drawn from a subclinical sample of 233 heterosexual couples recruited via an online survey. To account for the interdependent nature of the dyadic data, analyses were conducted using the Actor-Partner Interdependence Model (APIM) and its extension, the Actor-Partner Interdependence Moderation Model (APIMoM). The results indicated that relationships involving individuals with high levels of narcissism were characterized by more enacted and perceived negative dyadic coping (i.e. hostility and criticism), than relationships involving individuals with low levels of narcissism. This negative dyadic coping was amplified when trust levels were low. However, higher levels of trust were associated with improved dyadic coping processes, bringing them in line with those observed in relationships involving individuals with low levels of narcissism. Reduced enacted and perceived negative dyadic coping was linked to greater relationship commitment among individuals with high levels of narcissism, in a manner like that observed among individuals with low levels of narcissism. Overall, the findings suggest that trust may be a key mechanism that enables more responsive interaction patterns to emerge in relationships involving individuals with high levels of narcissism. By fostering trust, couples may be better able to develop and maintain functional romantic relationships despite elevated narcissistic levels

Pathways to sustainable agricultural investments in the Lao PDR: Transformations in natural resource and labour relations through land-based investments and their impacts on human well-being

After an initial boom in the early years of the millennium, global land-based investments, also called Large-Scale Land Acquisitions (LSLAs), have slowed in recent years, but their impact on local environments and human well-being still poses a challenge for fulfilling the 2030 Agenda for Sustainable Development. The debate on the effects of LSLAs lacks systematic assessment at the meso-level of spatial and administrative scale – a level that is critical for informing national policies. This research addresses that issue by first explaining how LSLAs entail differential impacts on local livelihoods, and second, by revealing how positive outcomes to these investments can be achieved in the context of the Global South. My analysis of the recent land concession inventory of the Lao PDR, including the scope, scale and socio-ecological context of LSLAs, reveals how land deals have impacted local livelihoods. They have transformed natural resources and labour relations by pushing former land users into precarious situations and onto pathways leading to different well-being outcomes. The affected villages have experienced different degrees of poverty increase or reduction. This research suggests that looking only at quantitative variables, especially the size of the land acquisitions, is a poor predictor of their socio-economic impacts. A better understanding of key variables is urgently needed to avoid both misinterpretations of the impact and misguided land-based investment policies. Using a methodological approach that includes an examination of monetary poverty, multiple dimensions of human well-being, primitive accumulation, and precarity, this research suggests that the pathway to improved human well-being in the context of LSLAs is very narrow. The decrease in monetary poverty in most villages has not resulted in positive human well-being outcomes. In terms of employment, which is the most important and immediate benefit that smallholders can enjoy, the findings reveal that in some cases, the peasants have experienced dispossession without proletarianization. In many cases, semi-proletarianization has occurred, but through adverse terms rather than could be part of a sustainable livelihood strategy. To avoid the negative impacts and ensure that land deals contribute to sustainable agricultural growth, this dissertation emphasizes four key points: 1) A comprehensive socio-environmental impact analysis and monitoring that includes natural resources such as non-timber forest products, timber and wild animals must be implemented rather than just focusing on the land itself. Implementation of the relevant accompanying measures must take place throughout the business cycle. Protecting access to the land and other resources is imperative as natural resources still play a significant role in rural resilience. This will ensure that smallholders, particularly women and vulnerable groups like ethnic minorities, can sustain their traditional livelihoods, especially during the transition period. 2) Adverse outcomes tend to occur in cases in which smallholders are dependent on natural resources for a living rather than already being engaged in the non-farm sector. Therefore, the development of LSAs must consider the socio-ecological heterogeneity of peasant livelihoods. 3) The International Code of Conduct (free, prior, and informed consent) per se does not guarantee positive well-being outcomes but it does provide space for consultation and negotiation. Thus, it is an important tool that should be applied by the investors, but should not be considered as the solution for safeguards. 4) Promoting land-based investments as a means of poverty reduction in rural areas by moving from the natural resource- to wage-based livelihoods is effective only with accompanying related measures. The national government should consider appropriate trade-offs among different development goals – for example, large-scale, labour-intensive investments may not significantly contribute to national growth but they may generate a higher number of jobs which may have a great positive impact on human well-being.ພາຍຫຼັງທີ ່ ໄດ້ມີການຂະຫຍາຍຕົວຢ່ າງໄວວາ ແລະ ກວ້າງຂວາງ, ການລົງທຶນໃນຂົງເຂດທີ ່ ດິນ ຫຼື ເອີ້ນ ວ່ າ ການເຊ່ າົ -ສໍາປະທານທ່ ດີ ນິ ຂະໜາດ ໃຫຍ່ (LSLAs) ຢ່ ູໃນໂລກໃນຊຸມປີມ່ ໆໍ ນ ີ້ ໄດມ້ ກີ ານຂະຫຍາຍຕວົ ຊາ້ ລງົ ແຕ່ ຜນົ ກະທບົ ຂອງມນັ ຕ່ ໍກບັ ສ່ ງິ ແວດລອ້ ມ ແລະ ການມຊີ ວີ ດິ ການ ເປັນຢູ ່ ທີ ່ ດີ (Human well-being) ຂອງທ້ອງຖິ ່ ນ ຍັງເປັນສິ ່ ງທ້າທາຍໜຶ ່ ງ ຕໍ ່ ກັບການບັນລຸເປົ້າໝາຍການພດັ ທະນາແບບຍນື ຍງົ ປີ 2030. ການຖົກຖຽງ ກ່ ຽວກັບ ຜົນກະທົບຂອງ LSLAs ແມ່ ນຍັງຂາດຂໍ້ມູນຫຼັກຖານ ທີ ່ ໄດ້ຈາກການວິເຄາະຂໍ້ມູນຢ່ າງເປັນລະບບົ ໃນລະດບັ ຊາດ ຊ່ ງຶ ເຫັນວ່ າ ມີຄວາມສໍາຄັນຫຼາຍ ຕໍ ່ ກັບນະໂຍບາຍແຫ່ ງຊາດ. ການຄົ້ນຄວາ້ ນ ີ້ ໄດປ້ ະກອບສ່ ວນໃນການປິດຊ່ ອງຫວ່ າງດ່ ງັ ກ່ າວ ໂດຍ ທໍາອດິ ໄດວ້ ິ ເຄາະເຖິງ ບັນດາຜົນກະທົບ ຂອງ LSLAs ຕໍ ່ ກັບຊີວິດການເປັນຢູ ່ ຂອງທ້ອງຖິ ່ ນ ວ່ າເກີດຂຶ້ນແນວໃດ ແລະ ຈາກນັ້ນ ໄດວ້ ເິ ຄາະເຖງິ ແນວທາງ ທ່ ສີ າມາດເຮດັ ໃຫກ້ ານລງົ ທນຶ ດ່ ງັ ກ່ າວ ມຜີ ນົ ໄດຮ້ ບັ ດາ້ ນບວກຢ່ ູໃນປະເທດກໍາລງັ ພດັ ທະນາ. ຜົນໄດ້ຮັບຈາກການວິເຄາະຂໍ້ມູນ ການຂຶ້ນ ບັນຊີໂຄງການເຊົ ່ າ ແລະ ສໍາປະທານທີ ່ ດິນ ຂອງລັດຢູ ່ ສປປ ລາວ ທີ ່ ມີຢູ ່ ລ້າສຸດ ຊຶ ່ ງລວມມີຂໍ້ມູນກ່ຽວ ກບັ ປະເພດ ແລະ ຂະໜາດ ຂອງການລງົ ທນຶ ຢ່ ູໃນ ສະພາບແວດລອ້ ມດາ້ ນເສດຖະກດິ -ສງັ ຄມົ ແລະ ນເິ ວດວທິ ະຍາຕ່ າງໆ ໄດສ້ ະແດງເຖງິ ຂະ ບວນການ ທ່ ໂີ ຄງການລງົ ທນຶ ດ່ ງັ ກ່ າວ ໄດສ້ ່ ງົ ຜນົ ກະທບົ ຕ່ ໍກບັ ຊວີ ດິ ການເປັນຢ່ ູຂອງທອ້ ງຖ່ ນິ . ການລງົ ທນຶ ເຫ່ ຼາົ ນ ີ້ ໄດປ້ ່ ຽນແປງສດິ ທກິ ານຖຄື ອງ ທີ ່ ດິນ ແລະ ສາຍພົວພັນດ້ານກໍາລັງແຮງງານ ໂດຍໄດ້ເຮັດໃຫ້ ເຈົ້າ ຂອງທ່ ດີ ນິ ຕອ້ ງຕກົ ຢ່ ູໃນສະພາບຄວາມບ່ ໍແນ່ ນອນ ແລະ ມລີ ະດບັ ຊວີ ດິ ການ ເປັນຢູ ່ ທີ ່ ແຕກຕ່ າງກັນ. ນອກນັ້ນ , ບ້ານທີ ່ ໄດ້ຮັບຜົນກະທົບ ມີລະດັບຄວາມທຸກຍາກເພີ ່ ມຂຶ້ນ ຫຼ ື ຫຸຼດລງົ ໃນລະດບັ ທ່ ບີ ່ ໍຄກື ນັ . ຜນົ ຂອງການ ຄົ້ນ ຄວ້ານີ້ ແນະນໍາວ່ າ ການທີ ່ ນໍາເອົາແຕ່ ຂໍ້ມູນດາ້ ນປະລມິ ານ ໂດຍສະເພາະແມ່ ນ ຂະໜາດຂອງທ່ ດີ ນິ ມາເປັນເກນໃນການປະເມນີ ແມ່ ນບ່ ໍ ເປັນຕົວຊີ້ວັດທີ ່ ດີ ໃນການປະເມີນຜົນກະທົບທາງດ້ານເສດຖະກິດ-ສັງຄົມ ຂອງ LSLAs ຊຶ ່ ງອາດນໍາໄປສູ ່ ການເຂົ້າໃຈທີ ່ ຜິດພາດ ກ່ ຽວກັບ ຜນົ ກະທບົ ຂອງມນັ ແລະ ອາດນາໍ ໄປສ່ ູການກາໍ ນດົ ນະໂຍບາຍທ່ ບີ ່ ໍສອດຄ່ ອງ. ໂດຍການນໍາໃຊບ້ ນັ ດາວທິ ກີ ານຕ່ າງໆ ລວມມ ີ ການປະເມນີ ຄວາມທຸກຍາກໂດຍອງີ ໃສ່ ລາຍຮບັ ເປັນຫຼກັ , ການມຊີ ວີ ດິ ການເປັນຢ່ ູທ່ ດີ ,ີ ການ ຄອບຄອງກໍາລັງການຜະລິດ ເພື ່ ອເຮັດໃຫ້ເຈົ້າ ຂອງທ່ ດີ ນິ ກາຍເປັນແຮງງານຮບັ ຈາ້ ງຢ່ ູທ່ ດີ ນິ ຂອງຕນົ (primitive accumulation and proletarianization) ແລະ ຄວາມບໍ ່ໝັ້ນ ຄົງ ຂອງຊີວິດ (precarity), ບົດຄົ້ນ ຄວ້ານີ້ ຊີ້ໃ ຫເ້ ຫນັ ວ່ າ ການຫຸຼດລງົ ຂອງອດັ ຕາຄວາມທຸກຍາກ ໂດຍອີງໃສ່ລາຍຮັບເປັນຕົ້ນຕໍ ຢູ ່ ຫຼາຍບ້ານທີ ່ ໄດ້ຮັບຜົນກະທົບນັ້ນ ບໍ ່ ໄດ້ໝາຍຄວາມວ່ າ ຊາວບ້ານຈະມີຊີວິດການເປັນຢູ ່ ທີ ່ ດີຂຶ້ນ . ມບີ າງກໍລະ ນີ, ປະຊາຊົນສູນເສຍທີ ່ ດິນໃຫ້ແກ່ ໂຄງການລົງທຶນ ແຕ່ ບໍ ່ ໄດ້ຮັບໂອກາດເຂົ້າ ເປັນແຮງງານຮບັ ຈາ້ ງ ແລະ ໃນຫຼາຍກໍລະນ ີ ຊາວບາ້ ນໄດກ້ າຍເປັນ ເຄ່ ງິ -ແຮງງານຮບັ ຈາ້ ງ ໂດຍຢ່ ູພາຍໃຕເ້ ງ່ອື ນໄຂແບບຄວາມຈາໍ ເປັນ ແທນທ່ ຈີ ະເປັນຍຸດທະສາດ ສໍາລບັ ຊວີ ດິ ການເປັນຢ່ ູແບບຍນື ຍງົ . ເພ່ ອື ຫຼກີ ລຽ້ ງ ຜນົ ກະທບົ ດາ້ ນລບົ ຈາກ LSLAs ແລະ ຮບັ ປະກນັ ວ່ າ ການລງົ ທນຶ ດ່ ງັ ກ່ າວ ປະກອບສ່ ວນເຮດັ ໃຫ ້ ການເຕບີ ໂຕດາ້ ນການຜະ ລິດກະສິກໍາແບບຍືນຍົງນັ້ນ , ຜົນໄດ້ຮັບຈາກການຄົ້ນ ຄວາ້ ນ ີ້ ສະທອ້ ນເຖງິ ສ່ ບີ ນັ ຫາທ່ ສີ ໍາຄນັ ທ່ ຄີ ວນຈະພຈິ າລະນາ ໄດແ້ ກ່ : ໜ່ ງຶ , ຕອ້ ງມ ີ ກນົ ໄກໃນການປະເມນີ ແລະ ຕດິ ຕາມ ຜນົ ກະທບົ ດາ້ ນສງັ ຄມົ ແລະ ສ່ ງິ ແວດລອ້ ມ ແບບຄບົ ຊຸດ ໂດຍຄໍານງຶ ເຖງິ ບນັ ດາຊບັ ພະຍາ ກອນທໍາມະຊາດອື ່ ນໆ ເຊັ ່ ນ: ເຄື ່ ອງປ່ າຂອງດົງ, ໄມ້ທ່ ອນ ແລະ ສັດປ່ າ ແລະ ອື ່ ນໆ ແທນທີຈະເນັ້ນໃສ່ ແຕ່ ທີ ່ ດິນ ແລະ ລວມທັງການຈັດຕັ້ງ ປະຕິບັດ ບັນດາມາດຕະການທີ ່ ຈໍາເປັນ ແລະ ເໝາະສົມ. ພ້ອມກັນນັ້ນ ການປົກປອ້ ງສດິ ທກິ ານນໍາໃຊທ້ ່ ດີ ນິ ແລະ ຊບັ ພະຍາກອນທໍາມະຊາດ ຂອງປະຊາຊນົ ຈ່ ງຶ ເຫນັ ວ່ າມຄີ ວາມສໍາຄນັ ຫຼາຍ ເນ່ ອື ງຈາກວ່ າ ຊບັ ພະຍາກອນທໍາມະຊາດ ຍງັ ມບີ ດົ ບາດສໍາຄນັ ຫຼາຍໃນການຮບັ ມກື ບັ ເຫດສຸກ ເສນີ . ຊ່ ງຶ ມນັ ຈະສາມາດຮບັ ປະກນັ ວ່ າ ຊາວກະສກິ ອນ ໂດຍສະເພາະແມ່ ນ ແມ່ ຍງິ ແລະ ກ່ ຸມສ່ ຽງ ເຊ່ ນັ : ກ່ ຸມຊນົ ເຜ່ າົ ສ່ ວນນອ້ ຍ ສາມາດສບື ຕ່ ໍ ການດໍາລງົ ຊວີ ດິ ທ່ ເີ ຄຍີ ປະຕບິ ດັ ຜ່ ານມາໄດ ້ ໂດຍສະເພາະແມ່ ນ ໃນຊ່ ວງໄລຍະເວລາຂາ້ ມຜ່ ານ. ສອງ, ຜົນກະທົບດ້ານລົບຂອງການລົງທຶນມັກຈະເກີດຂຶ້ນ ໃນກໍລະນທີ ່ ີ ຊາວບາ້ ນຍງັ ອາໄສຊບັ ພະຍາກອນທໍາມະຊາດ ໃນການດໍາລງົ ຊວີ ດິ ເປັນຕົ້ນ ຕໍ ເມື ່ ອທຽບໃສ່ ກໍລະນີ ທີ ່ ຊາວບ້ານໄດ້ຫັນໄປສູ ່ ຂະແໜງການອື ່ ນທີ ່ ບໍ ່ ແມ່ ນການກະສິກໍາແລ້ວ. ສະນັ້ນ , ຈ່ ງຶ ແນະນໍາວ່ າ ຂະບວນການ ຕດັ ສນິ ໃຈ ຫຼ ື ວາງແຜນ ຄວນມກີ ານພຈິ າລະນາເຖງິ ຄວາມແຕກຕ່ າງຂອງປະຊາຊນົ ຢ່ ູໃນແຕ່ ລະເຂດ. ສາມ, ຫກຼັ ການ ກ່ ຽວກບັ ຄວາມສອດຄ່ ອງຂອງສາກນົ (Code of Conduct) ເຊ່ ນັ : ການເຫນັ ດ ີ ເຫນັ ພອ້ ມ ໂດຍມກີ ານຕດັ ສນິ ໃຈຢ່ າງ ອດິ ສະຫຼະ ແລະ ມກີ ານແຈງ້ ລ່ ວງໜາ້ ຢ່ າງດຽວ ແມ່ ນບ່ ໍສາມາດ ຮບັ ປະກນັ ຜນົ ໄດຮ້ ບັ ທາງດາ້ ນບວກໄດ ້ ແຕ່ ມນັ ຕອບສະໜອງ ໂອກາດ ໃນ ການປຶກສາຫາລື ແລະ ການເຈລະຈາໃຫ້ແກ່ ຊຸມຊົນ. ສະນັ້ນ , ຫຼກັ ການເຫ່ ຼາົ ນ ີ້ ແມ່ ນຄວນເປັນເຄ່ ອື ງມທື ່ ສີ ໍາຄນັ ທ່ ນີ ກັ ລງົ ທນຶ ຕອ້ ງນາໍ ໃຊ ້ ແຕ່ ບ່ ໍ ຄວນຖວື ່ າມນັ ເປັນທາງອອກ ສໍາລບັ ການປົກປອ້ ງຜນົ ກະທບົ ດາ້ ນສງັ ຄມົ . ສຸດທາ້ ຍ, ເຫນັ ວ່ າ ການສ່ ງົ ເສມີ ການລງົ ທນຶ ໃສ່ ທ່ ດີ ນິ ເພ່ ອື ເປັນເຄ່ ອື ງມໜື ່ ງຶ ໃນການຫຸຼດຜ່ ອນຄວາມທຸກຍາກຢ່ ູເຂດຊນົ ນະບດົ ໂດຍການຫນັ ຈາກ ການອາໄສຊບັ ພະຍາກອນທໍາມະຊາດ ໄປສ່ ູການເປັນແຮງງານຮບັ ຈາ້ ງ ແມ່ ນມປີ ະສດິ ທຜິ ນົ ຖາ້ ຫາກມ ີ ບນັ ດາມາດຕະການທ່ ຈີ າໍ ເປັນ. ສະນັ້ນ , ຈຶ ່ ງເຫັນວ່ າ ລັດຖະບານ ຈະຕ້ອງໄດ້ພິຈາລະນາເລືອກ (trade-offs) ລະຫວ່ າງ ເປົ້າ ໝາຍ ຂອງການພັດທະນາ - ຕົວຢ່າງ ໂຄງການ ລງົ ທນຶ ຂະໜາດໃຫຍ່ ແລະ ນໍາໃຊແ້ ຮງງານຄນົ ເປັນຫຼກັ ອາດບ່ ໍປະກອບສ່ ວນຫຼາຍປານໃດ ຕ່ ໍກບັ ການເຕບີ ໂຕແຫ່ ງຊາດ ແຕ່ ມນັ ອາດສາ້ ງວຽກ ເຮດັ ງານທໍາໄດຫ້ ຼາຍກວ່ າ

Poisson convergence in stochastic geometry via generalized size-bias coupling

This dissertation aims to investigate several aspects of the Poisson convergence: Poisson approximation, multivariate Poisson approximation, Poisson process approximation and weak convergence to a Poisson process. The size-bias coupling is a powerful tool that, when combined with the Chen-Stein method, leads to many general results on Poisson approximation. We define an approximate size-bias coupling for integer-valued random variables by introducing error terms, and we combine it with the Chen-Stein method to compare the distributions of integer-valued random variables and Poisson random variables. In particular, we provide explicit bounds on the pointwise difference between the cumulative distribution functions. By these findings, we show approximation results in the Kolmogorov distance for minimal circumscribed radii and maximal inradii of stationary Poisson-Voronoi tessellations. Moreover, we compare the distributions of Poisson random variables and U-statistics with underlying Poisson processes or binomial point processes, which, in particular, allows us to approximate the rescaled minimum Euclidean distance between pairs of points of a Poisson process with midpoint in an observation window by an exponentially distributed random variable using the Kolmogorov distance. A multivariate version of the size-bias coupling is employed to investigate the Gaussian approximation for random vectors by L. Goldstein and Y. Rinott. We extend the notion of approximate size-bias coupling for random variables to random vectors, and we combine it with the Chen-Stein method to investigate the multivariate Poisson approximation in the Wasserstein distance and the Poisson process approximation in a new metric defined herein. As an application, we obtain a bound on the Wasserstein distance between the sum of m-dependent Bernoulli random vectors and a Poisson random vector. Moreover, we consider point processes of U-statistic structure, that is, point processes that, once evaluated on a measurable set, become U-statistics. For point processes of U-statistic structure with an underlying Poisson process, we establish a Poisson process approximation result that is the analogue of the one shown by L. Decreusefond, M. Schulte, and C. Thäle with the Kantorovich-Rubinstein distance replaced by our new metric. General criteria for the weak convergence of locally finite point processes to a Poisson process are derived from the relation between probabilities of two consecutive values of a Poisson random variable. P. Calka and N. Chenavier studied the limiting behavior of characteristic radii of homogeneous Poisson-Voronoi tessellations. By our general results, we extend and improve their findings by showing Poisson process convergence for point processes constructed using inradii and circumscribed radii of inhomogeneous Poisson-Voronoi tessellations

Use of biomarkers in ischemic strokes : the particular case of cancer-related strokes

Background: Around 5–10% of all patients with acute ischemic stroke (AIS) have underlying active cancer at the time of their stroke and constitute the group of “cancer-related strokes”. Cancer patients are known to have a higher risk of first and recurrent AIS, more severe stroke, and increased mortality after AIS. Although cancer-related strokes are thought to be caused by paraneoplastic coagulopathy, the complex relationship between cancer and AIS remains difficult to understand due to the multitude of cancer types and differing stages of cancer progression at the time of AIS. Consequently, it is essential to improve our knowledge of cancer-related strokes and the management of the affected patients. The general aim of this PhD thesis was to elucidate the description of the incidence, characteristics and outcomes of cancer-related strokes. Methods: The analyses that make up this PhD thesis are grouped into three subchapters corresponding to its three specific aims: The first was to better understand the characteristics of known biomarkers for cancer-related strokes and to identify new and, if possible, specific biomarkers of cancer-related strokes. Such biomarkers are essential for assessing the severity of paraneoplastic coagulation, identifying patients at risk of underlying undetected cancer at the time of AIS (occult cancer) and assessing the prognosis of AIS patients with underlying active cancer. The second aim was the investigation of AIS due to occult cancer. By proposing a clinical score to predict the presence of underlying occult cancer and investigating the outcomes for AIS patients with occult cancer, we sought to support the future implementation of a cancer-screening procedure in high-risk AIS patients. The third aim was to investigate factors influencing the outcomes of cancer-related strokes. In addition to assessing the influence of biomarkers associated with cancer-related strokes on long-term outcomes after AIS, we investigated which type of antithrombotic drug was associated with the best outcomes in patients with cancer-related stroke. To meet the aims of this PhD thesis, we created the Bernese Malignancy-in-Stroke (BMS) Database, which included cancer-specific data from all consecutive AIS patients treated between 2015 and 2020 at the Inselspital, University Hospital of Bern, Switzerland (N=5012). In parallel, we created the Bernese Transient Ischemic Attack (TIA) Database, which included data on all consecutive TIA patients treated at the Inselspital between 2015 and 2020 (N=1436). We used TIA patients without persisting brain damage as a comparison group in some of the studies presented in this thesis. Results: In this PhD thesis, we demonstrated that common cancer-associated biomarkers in AIS patients were also present in TIA patients with cancer. Compared to TIA patients without cancer, those with cancer were more likely to have a history of smoking (adjusted odds ratio [aOR] 2.77, 95% confidence interval [CI] 1.34–5.7), elevated D-dimer (aOR 1.77, 95% CI 1.26–2.49), elevated lactate dehydrogenase (aOR 1.003, 95% CI 1.00–1.005), lower hemoglobin (aOR 1.02, 95% CI 1.00–1.04), and lower leukocyte count (aOR 1.20, 95% CI 1.04–1.38). In AIS patients (independently of the presence of cancer), we demonstrated a time-dependent fluctuation in D-dimer levels. An early increase in D-dimer levels occurred within the first 6 hours after symptom onset (standardized beta coefficient [β] 0.728, 95% CI 0.324–1.121). Following this initial increase, the levels decreased (β −13.022, 95% CI −20.401 to −5.643) and a second increase was seen after 35 hours from symptom onset (β 11.750, 95% CI 4.71–18.791). No time-dependent fluctuation in D-dimer levels was observed in the control group of patients with TIA. In our study on the identification of new biomarkers for cancer-related strokes, we demonstrated an association between active cancer and the susceptibility vessel sign (SVS), a non-invasive, in situ representation of an occlusive thrombus, reflecting its microscopic composition. The absence of the SVS was associated with the presence of cancer in AIS patients (aOR 3.14, 95% CI 1.45–6.80). In another study, we demonstrated an association between the absence of a right-to-left cardiac shunt (encompassing patent foramen ovale and atrial septal defect) and active cancer (aOR 2.29, 95% CI 1.14–4.58). We were unable to demonstrate any association between increased left atrial volume index (≥35 mL/m2 on echocardiography), representing atrial cardiopathy, and the presence of cancer in patients with AIS (aOR 0.91, 95% CI 0.60–1.37). Based on our studies on occult cancers, we proposed the OCCULT-5 Score, which comprises five variables: age ≥ 77 years, embolic stroke of undetermined source, multi-territorial brain infarcts, D-dimer levels ≥ 820 μg/L, and female sex. A score of ≥ 3 predicted an underlying occult cancer in AIS patients, with a sensitivity of 64% and a specificity of 73%. Outcomes in patients with new cancer diagnosed immediately after the index AIS (during hospitalization) were no better than those with a cancer diagnosis obtained after discharge and within one year after the index AIS. In particular, there was no difference in long-term mortality between patient groups (adjusted hazard ratio [aHR] 1.16, 95% CI 0.53–2.52). Regarding factors influencing outcomes, in AIS patients treated with mechanical thrombectomy, we demonstrated an association between the absence of the SVS and long-term mortality (aHR 2.11, 95% CI 1.35–3.29) and poor functional outcome in the long term (aOR 2.90, 95% CI 1.29–6.55). Interaction analyses did not reveal any substantial influence of the presence of active cancer on these associations (p for interaction=0.79 and 0.71, respectively). Finally, there was no difference in outcomes between the two types of antithrombotic drug used for secondary prevention in AIS patients with active cancer. Anticoagulant and antiplatelet therapy were associated with similar risks of 1-year mortality (aHR 0.76, 95% CI 0.36–1.63) and long-term recurrent AIS (aHR 0.49, 95% CI 0.08–2.83). Discussion: The projects comprising this PhD thesis covered many aspects of the “cancer-related stroke” field. The absence of the SVS, reflecting the predominance of platelets and fibrin in the microscopic composition of the occluding thrombus, was associated with cancer-related strokes (and also independently associated with platelet- and fibrin-rich thrombi). Since the presence of the SVS, by contrast, was mainly associated with erythrocyte-rich thrombi and cardioembolic AIS, the assessment of SVS status (giving us a direct insight into the thrombus composition in situ) is helpful to assess the most likely underlying stroke etiology. An association between active cancer and arterial causes of AIS is presumed due to the negative association with right-to-left cardiac shunts (as a surrogate marker for paradoxical embolism). Furthermore, our studies showed a trend towards non-cardioembolic causes of AIS in patients with active cancer due to the association with absence of the SVS and the lack of association with atrial cardiopathy. As only 1.4% of AIS patients are diagnosed with a new cancer in the year following an AIS (and up to 6.2% following cryptogenic strokes), it is important to identify patients at risk of occult cancer to speed up the time to cancer diagnosis and potentially positively influence patient outcomes. To our knowledge, our OCCULT-5 Score is the only model that provides a clinical score that can be easily used at the bedside to evaluate the probability of underlying occult cancer in AIS patients. Despite the large size of our BMS, only 59 patients with occult cancer were included in the study, which failed to demonstrate a difference in outcomes between patients diagnosed with a new cancer during hospitalization versus after discharge. This underscores the need for multicenter studies that include larger numbers of AIS patients with active cancer, and particularly occult cancers, to address unanswered research questions. Finally, regarding secondary prevention, there are no conclusive guideline-based recommendations for the optimal antithrombotic strategy for patients with cancer-related strokes. Although our study (not published yet) on whether anticoagulants or antiplatelet drugs offered better secondary prevention has the advantage of including only patients with active cancer, it failed to demonstrate an advantage for either medication emphasizing the need for randomized clinical trials on this subject in the future. Outlook: The establishment of a multicenter registry of cancer-related strokes with detailed information on individual cancers will enable investigators to perform studies analyzing the different types of cancer on a case-by-case basis, and potentially to propose individualized treatments. In addition, prospective studies are needed, both to assess the risk of occult cancer in AIS patients and to evaluate new biomarkers for cancer-related strokes

Analysis of bovine intramammary bacteriome, resistome and of the bacterial transmission within dairy herds

Mastitis is the most important and costly disease in dairy cows worldwide. Bovine intramammary infection (IMI) caused by pathogenic bacteria is common and well understood but very little is known about the bacteria and their resistome present in the mammary gland (= intramammary resistome, IR) of healthy and untreated cows whose milk is regularly delivered for human consumption. The aim that our research project wanted to: i) describe the bacteriome of healthy cows means all the bacteria that we can isolate from the milk of healthy cow, ii) describe the resistome means the antibiotic resistance correlated with the bacteriome isolated with the use of phenotypic and genomic methods iii) comparison of the bacteriome and resistome with the environmental isolates. Healthy, untreated cows of nine dairy herds from the Swiss Canton Tessin were analyzed three times within one year to identify the most abundant species of the intramammary bacteriome of healthy animals. Aseptically collected milk samples were cultured and bacteria identified using MALDI-TOF mass spectrometry. To describe the intramammary resistome, 350 strains of the predominant species were selected and subjected to short-read based whole genome sequencing (WGS) combined with phenotypic analyses and antibiotic resistance gene profiling. Both chromosomes and mobile genetic elements were examined for antibiotic resistance genes (ARGs) using in-house and online software tools. ARGs were then associated with phenotypic antibiotic resistance profiling data from minimum inhibitory concentration assays. Furthermore, the phylogeny of the two main species isolated Staphylococcus xylosus (S. xylosus) and Mammaliicoccus sciuri (M. sciuri) was assessed using 70 housekeeping genes and the maximum likelihood approach (PhyML). Additionally statistical analyses were carried out. Of 256 cows (1024 single quarters) analyzed, 96% were bacteriologically positive and 80% of the quarters were positive for at least one bacterial species. 84.5% of the quarters were healthy with somatic cell counts (SCC) < 200’000 cells/ml, whereas 15.5% of the quarters showed a subclinical mastitis (SCC ≥ 200’000 cells/ml). The 1288 isolates were assigned to 104 different bacterial species including 24 predominant species. Staphylococcaceae were most prevalent (14 different species; 73.5% bacteria-positive quarters) with S. xylosus and M. sciuri accounting for 41.5% of the strains. Our study demonstrates that Staphylococcaceae could be consider part of the healthy milk bacteriome. Furthermore, the different farm-specific patterns of the bacteriome are associated with the use of different bedding in the herd. The non-aureus staphylococci and mammalicocci (NASM) have been regarded as minor mastitis pathogens being the most abundantly observed bacteria in mastitis milk samples. Based on our study, however, their function needs to be reconsidered. We could assume that different subtypes of NASM may colonize the mammary gland whereas other subtypes may cause minor mastitis. Phenotypic and genomic antimicrobial resistance (AMR) was bacterium-specific whereby resistance to clindamycin and oxacillin was most frequently observed (40% and 30%). In contrast, AMR to penicillin, although massively used for mastitis treatment during last decades, was rarely observed. The phenotypic findings, not in all the cases, could be linked to chromosomal or plasmid-borne ARGs, demonstrating a lack in understanding the mechanisms that lead to the observed phenotypic AMRs in the isolated bacteria. For some species/AMR, the observed phenotypic AMR could be explained. This is true for M. sciuri and its resistance to clindamycin (salA gene) as well as S. xylosus, M. sciuri and a few other bacteria in the case of tetracycline. For all of them, a small plasmid was found carrying the tetK or another tetracycline ARG. The presence of tetracycline AMR was herd dependent and was observed in various isolates of the same farm indicating a possible horizontal gene transfer among the different bacteria on the same farm, particularly among S. xylosus and M. sciuri. The phylogenetic studies involved S. xylosus and M. sciuri; these bacteria were the most abundant isolated and were collected from both milk and environmental samples. M. sciuri was found predominantly in environmental samples (particularly straw bedding and teat liners before milking). Differently, the S. xylosus strains were mostly isolated from milk samples. Based on these results we could conclude that S. xylosus is mainly udder adapted whereas the habitat of M. sciuri is more environmentally related. Detailed phylogenetic analyses for M. sciuri revealed two main clades whereby the smaller one included the M. sciuri type strain. Typically, the strains forming this clade were almost exclusively isolated from bedding, milk, and teats, whereas those of the other clade were isolated from milk, teats, and liners, but hardly from bedding. These results suggest that M. sciuri circulates clade dependently more among environment and mammary gland (type strain clade) whereas M. sciuri of the other clade circulates more among mammary gland and milking equipment. These findings are confirmed by genotype analysis, inferring MLST, demonstrating that the distribution of the sequence types (STs) between milk and environment revealed only a few common STs. Interestingly, M. sciuri showed a remarkable variability at the STs level with the consequence that a number of different STs were observed on the same farm. In the case of S. xylosus, three main clades were observed. As in M. sciuri, the phylogenetic distances within each clade were very small showing that the taxa/strains evolved minimally and that they are genetically very similar. For all three clades, the taxa were largely milk associated whereas environmental taxa were hardly observed. These findings indicate that S. xylosus circulates primarily among mammary glands and the taxa found in the environment are more the result of a contamination by milk. As a conclusion, the research project demonstrates that bacteria, particularly NASM, are very common in the mammary gland of healthy cows, a fact that needs to be considered when interpreting bacteriological results obtained from clinical milk samples. Furthermore, AMR in NASM is uncommon, also against penicillin, although it has been massively used for mastitis treatment during last decades. Unfortunately, AMR in these bacteria remains largely unexplained by genomic analyses. Furthermore, AMR against antibiotics used in human medicine is rare. Finally, phylogenetic studies demonstrate that M. sciuri and S. xylosus formed only a few major clades and within each clade the strains were genetically very similar; for M. sciuri the habitat was clade dependent. It is essential to get more knowledge about the bacteriome of the mammary glands of healthy and diseased cows to understand the microbiota, hinder pathogens to gain a foothold and, in the long term, prevent the development and spread of resistances. WGS represents an important tool for detecting ARGs but still needs to be associated with phenotypic analysis and with gene and/or protein expression analyses. Screening for new genes associated with AMR and an increase of the ARG databases will be essential, especially for the One Health concept