@phdthesis{Braun2021, author = {Braun, Alexandra}, title = {Psychosocial and somatic resilience factors of patients with fibromyalgia syndrome (FMS)}, doi = {10.25972/OPUS-24280}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242809}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Background: In recent years, health care has increasingly become the focus of public interest, politics, health insurance companies, and research. This includes the development of therapeutic concepts that can respond individually to patients' resources in order to improve coping with chronic diseases. Research into psychosocial and biological resilience factors is very important and the basic objective of the present work. I studied patients with fibromyalgia syndrome (FMS), who suffer among others from chronic pain, fatigue, sleep and gastrointestinal problems. This patient cohort is characterized by a pronounced heterogeneity in terms of clinical outcome, degree in disability and coping. FMS has a prevalence of 3 - 8 \% in the Western population and has a significant socio-economic impact. Validated psychosocial resilience factors include optimism, humor, coherence, self-efficacy, awareness with one's own resources and the ability to apply them profitably (coping), and a healthy social environment with positive relationships. Studies in patients with cancer revealed religiosity as positive and negative factor on the health outcome, but there is little data on religious aspects of pain resilience. Various genetic polymorphisms and anti-inflammatory cytokines are known as biological resilience factors. Various microRNA (miRNA) were detected to contribute to resilience in the context of stress and psychiatric disorders. Objective: The underlying research question of this work is to understand the factors that make some FMS patients resilient and others not, even though they suffer from the same disease. The long-term aim was to understand mechanisms and influencing factors of resilience to design preventive and resource-oriented therapies for FMS patients. Material and Methods: Three studies examined religious, physiological, biological, and psychosocial factors which may contribute to resilience in FMS patients. Study one combined data of questionnaires, a psychosocial interview, and regression analyses to investigate the relevance of religiosity for coping and resilience. Study two examined variance explaining factors and defined clusters among FMS patients by their differences in coping, pain phenotype and disability. The factor analysis used variables derived from questionnaires and qPCR of cytokines in white blood samples (WBC) of patients and healthy controls. Study three assessed cluster-wise miRNA signatures which may underly differences in behaviour, emotional and physiological disability, and resilience among patient clusters. A cluster-specific speculative model of a miRNA-mediated regulatory cycle was proposed and its potential targets verified by an online tool. Results: The data from the first study revealed a not very religious patient cohort, which was rather ambivalent towards the institution church, but described itself as a believer. The degree of religiosity played a role in the choice of coping strategy but had no effect on psychological parameters or health outcomes. The coping strategy "reinterpretation", which is closely related iv to the religious coping "reappraisal", had the highest influence on FMS related disability. Cognitive active coping strategies such as reappraisal which belongs to religious coping had the highest effect on FMS related disability (resilience) and could be trained by a therapist. Results from the second study showed high variances of all measured cytokines within the patient group and no difference between patient and control group. The high dispersion indicated cluster among patients. Factor analysis extracted four variance-explaining factors named as affective load, coping, pain, and pro-inflammatory cytokines. Psychological factors such as depression were the most decisive factors of everyday stress in life and represented the greatest influence on the variance of the data. Study two identified four clusters with respective differences in the factors and characterized them as poorly adapted (maladaptive), well adapted (adaptive), vulnerable and resilient. Their naming was based on characteristics of both resilience concepts, indicated by patients who were less stress-sensitive and impaired as a personal characteristic and by patients who emerged as more resilient from a learning and adaptive process. The data from the variance analysis suggests that problem- and emotion-focused coping strategies and a more anti-inflammatory cytokine pattern are associated with low impairment and contribute to resilience. Additional favorable factors include low anxiety, acceptance, and persistence. Some cluster-specific intervention proposals were created that combine existing concepts of behavioral and mindfulness therapies with alternative therapies such as vitamin D supplementation and a healthy intestinal flora. The results of the third study revealed lower relative gene expression of miR103a-3p, miR107, and miR130a-3p in the FMS cohort compared to the healthy controls with a large effect size. The adaptive cluster had the highest gene expression of miR103a-3p and tendentially of miR107, which was correlated with the subscale score "physical abuse" of the trauma questionnaire. Further correlations were found in particular with pain catastrophizing and FMS-related disability. MiR103a-3p and miR107 form a miRNA-family. Based on this, we proposed a miR103a/107 regulated model of an adaptive process to stress, inflammation and pain by targeting genetic factors which are included in different anti-inflammatory and stress-regulating pathways. Conclusion: All three studies provide new insights into resilience in FMS patients. Cognitive coping (reappraisal/reinterpretation) plays a central role and thus offers therapeutic targets (reframing in the context of behavioral therapy). Religosity as a resilience factor was only partially valid for our patient cohort. Basically, the use of resource-oriented therapy in large institutions still requires research and interdisciplinary cooperation to create a consensus between the humanities, natural sciences and humanism.}, subject = {Resilienz}, language = {en} } @phdthesis{Dischinger2015, author = {Dischinger, Ulrich Severin}, title = {Auswirkungen unterschiedlicher Haltungsbedingungen auf Ph{\"a}notyp und Genexpression im Mausmodell}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142955}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {In zahlreichen Untersuchungen konnte gezeigt werden, dass Umweltbedingungen im fr{\"u}hen Lebensalter einerseits die Entwicklung von Resilienz, d.h. Widerstandsf{\"a}higkeit gegen{\"u}ber Stressoren, andererseits aber auch die Entwicklung physischer und psychischer Erkrankungen im weiteren Lebensverlauf beeinflussen k{\"o}nnen. Dabei wird angenommen, dass sich sowohl dezidiert positive als auch in Maßen aversive Umweltbedingungen mit rezidivierender Stressbelastung g{\"u}nstig auf die Resilienz im sp{\"a}teren Leben auswirken k{\"o}nnen. Auf neurobiologischer Ebene scheinen dabei das CRH und seine Rezeptoren (CRHR1 und CRHR2), das NPY-System sowie das NPS-System (insbesondere NPS-Rezeptor) eine besondere Rolle zu spielen. Jedoch sind die exakten Zusammenh{\"a}nge und neurobiologischen Grundlagen weiterhin nur unzureichend aufgekl{\"a}rt. Dies ist insbesondere insofern bedauernswert, da weiterer Erkenntnisgewinn auf diesem Gebiet m{\"o}glicherweise Pr{\"a}ventionsstrategien und Therapieoptionen f{\"u}r den Menschen begr{\"u}nden k{\"o}nnte. Um die Auswirkung der Umweltbedingungen im fr{\"u}hkindlichen Lebensalter auf die Resilienz im sp{\"a}teren Leben weiter aufzukl{\"a}ren, wurden im Rahmen dieser Arbeit insgesamt 310 Cd1-M{\"a}use den Haltungsbedingungen "Environmental Enrichment" (EE, Stimulation durch Spielobjekte) und "Maternal separation" (MS, wiederholte Stressbelastung durch Separation der Nachkommen vom Muttertier) sowie Standardhaltungsbedingungen unterworfen. Insgesamt 31 m{\"a}nnlichen Tieren wurde im Alter von vier Wochen die Gehirne entnommen und aus diesen jeweils die Regionen Frontalcortex, Striatum, Nucleus accumbens, Hippocampus, Amygdala, dorsale Nuclei raphes und Hypothalamus herauspr{\"a}pariert. Aus den gewonnenen Proben wurde RNA extrahiert, hieraus cDNA synthetisiert und abschließend - nach Ausschluss von Kontamination und Integrit{\"a}tspr{\"u}fung - die Expressionsraten der untersuchten Gene mittels RT-qPCR quantifiziert. Um auch verhaltensbiologische Konsequenzen der unterschiedlichen Haltungsbedingungen zu erfassen, wurden außerdem 30 weibliche sowie 30 m{\"a}nnliche Tiere im weiteren Lebensverlauf verschiedenen Verhaltenstests zugef{\"u}hrt. In den Sucrose-Pr{\"a}ferenz-Tests zeigten sich Effekte der Haltungsbedingung auf Sucrose-Konsum und Pr{\"a}ferenz mit signifikant geringeren Werten der Haltungsgruppe EE. Bei der Auswertung der Openfield-Tests fanden sich Gruppen-Geschlechter-Interaktionseffekte mit signifikant geringeren Werten (Gesamtstrecke, Strecke und Aufenthaltsdauer im zentralen Bereich, Eintritte in den zentralen Bereich) der weiblichen EE-Tiere. In den Barnes Maze-Tests ben{\"o}tigten die Tiere der Haltungsgruppe EE an den meisten Testtagen signifikant weniger Zeit, um in die Escape-Box zu "entkommen". Auf neurobiologischer Ebene fanden sich signifikante Unterschiede der CRH-Expressionsraten in Amygdalae und Frontalcortex, der CRHR 1-Expressionsraten in Amygdalae und Hypothalamus sowie der CRHR2-Expressionsraten in Amygdalae und Hippocampus. Demgegen{\"u}ber konnte kein signifikanter Effekt der Haltungsbedingung auf das NPY-System gefunden werden. Jedoch ließen sich signifikante Unterschiede der NPSR1-Expressionsraten in Amygdalae, Frontalcortex, dorsalen Nuclei raphes und Hypothalamus feststellen. Es kann also grunds{\"a}tzlich von Auswirkungen unterschiedlich aversiver Haltungsbedingungen auf die Stress-Resilienz von Versuchstieren ausgegangen werden. Dies ist einerseits f{\"u}r Tierversuche allgemein von grunds{\"a}tzlicher Bedeutung. Andererseits legen die Resultate eine entsprechende fr{\"u}hkindliche "Programmierung" auch im Menschen nahe.}, subject = {Stress}, language = {de} } @phdthesis{Martin2008, author = {Martin, R{\"u}diger}, title = {Resilience, Provisioning, and Control for the Network of the Future}, doi = {10.25972/OPUS-2504}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-28497}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {The Internet sees an ongoing transformation process from a single best-effort service network into a multi-service network. In addition to traditional applications like e-mail,WWW-traffic, or file transfer, future generation networks (FGNs) will carry services with real-time constraints and stringent availability and reliability requirements like Voice over IP (VoIP), video conferencing, virtual private networks (VPNs) for finance, other real-time business applications, tele-medicine, or tele-robotics. Hence, quality of service (QoS) guarantees and resilience to failures are crucial characteristics of an FGN architecture. At the same time, network operations must be efficient. This necessitates sophisticated mechanisms for the provisioning and the control of future communication infrastructures. In this work we investigate such echanisms for resilient FGNs. There are many aspects of the provisioning and control of resilient FGNs such as traffic matrix estimation, traffic characterization, traffic forecasting, mechanisms for QoS enforcement also during failure cases, resilient routing, or calability concerns for future routing and addressing mechanisms. In this work we focus on three important aspects for which performance analysis can deliver substantial insights: load balancing for multipath Internet routing, fast resilience concepts, and advanced dimensioning techniques for resilient networks. Routing in modern communication networks is often based on multipath structures, e.g., equal-cost multipath routing (ECMP) in IP networks, to facilitate traffic engineering and resiliency. When multipath routing is applied, load balancing algorithms distribute the traffic over available paths towards the destination according to pre-configured distribution values. State-of-the-art load balancing algorithms operate either on the packet or the flow level. Packet level mechanisms achieve highly accurate traffic distributions, but are known to have negative effects on the performance of transport protocols and should not be applied. Flow level mechanisms avoid performance degradations, but at the expense of reduced accuracy. These inaccuracies may have unpredictable effects on link capacity requirements and complicate resource management. Thus, it is important to exactly understand the accuracy and dynamics of load balancing algorithms in order to be able to exercise better network control. Knowing about their weaknesses, it is also important to look for alternatives and to assess their applicability in different networking scenarios. This is the first aspect of this work. Component failures are inevitable during the operation of communication networks and lead to routing disruptions if no special precautions are taken. In case of a failure, the robust shortest-path routing of the Internet reconverges after some time to a state where all nodes are again reachable - provided physical connectivity still exists. But stringent availability and reliability criteria of new services make a fast reaction to failures obligatory for resilient FGNs. This led to the development of fast reroute (FRR) concepts for MPLS and IP routing. The operations of MPLS-FRR have already been standardized. Still, the standards leave some degrees of freedom for the resilient path layout and it is important to understand the tradeoffs between different options for the path layout to efficiently provision resilient FGNs. In contrast, the standardization for IP-FRR is an ongoing process. The applicability and possible combinations of different concepts still are open issues. IP-FRR also facilitates a comprehensive resilience framework for IP routing covering all steps of the failure recovery cycle. These points constitute another aspect of this work. Finally, communication networks are usually over-provisioned, i.e., they have much more capacity installed than actually required during normal operation. This is a precaution for various challenges such as network element failures. An alternative to this capacity overprovisioning (CO) approach is admission control (AC). AC blocks new flows in case of imminent overload due to unanticipated events to protect the QoS for already admitted flows. On the one hand, CO is generally viewed as a simple mechanism, AC as a more complex mechanism that complicates the network control plane and raises interoperability issues. On the other hand, AC appears more cost-efficient than CO. To obtain advanced provisioning methods for resilient FGNs, it is important to find suitable models for irregular events, such as failures and different sources of overload, and to incorporate them into capacity dimensioning methods. This allows for a fair comparison between CO and AC in various situations and yields a better understanding of the strengths and weaknesses of both concepts. Such an advanced capacity dimensioning method for resilient FGNs represents the third aspect of this work.}, subject = {Backbone-Netz}, language = {en} }