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Palaeodemography and palaeopathology in early mediaeval Säben-Sabiona, South Tyrol, Italy
Get PDFThe early mediaeval period was characterised by continuous variations of frontiers, leadership, and consequently also socio-economic instabilities. Located in the central Alps, along one of the most important passageways between Germany and Italy, the episcopal see of Säben-Sabiona played a central role and was particularly affected by these fluctuations. The site is located on a mount in the Eisack-Isarco valley, which, starting from the 7th century A.D. was occupied by Germanic groups, such as Bavarians and Longobards. Three archaeological excavations uncovered a palaeochristian church, dated to the 5th-8th centuries A.D., featuring between 366 and 370 graves. Due to the quantity of burials and wealth of some of these, Säben-Sabiona is regarded as the largest early mediaeval burial site in South Tyrol and the only one evidencing an admixture of autochthonous, i.e., local Romans, and allochthonous groups, i.e., Bavarians and/or Longobards.
Up to date, only detailed historical and archaeological investigations concerning the palaeochristian church were accomplished, yet the anthropological analysis of these remains was still outstanding. As the first anthropological study ever performed on this site, the present thesis focused on establishing the palaeodemographic composition as well as the living and health conditions of the individuals buried within and surrounding the palaeochristian church. Due to the unavailability of skeletal remains from earlier archaeological investigations and the limited archaeological and historical contextualisation of these, the present anthropological analysis focused on the subpopulation addressed in the publication by Bierbrauer and Nothdurfter (2015). A traditional osteological approach to endeavour this aim was predefined, after consulting with my supervisors. A full anthropological analysis, i.e., consisting of the biological and pathological profile of the human skeletal remains, recovered during the last excavation, i.e., 185 graves, was performed. The biological profile included the estimation of the minimum number of individuals, sex, age at death, stature, body weight and robusticity. These data were used to perform further palaeodemographic analyses, such as estimation of the masculinity index, the probability of dying at a certain age, the average life expectancy at different ages and population size. Additionally, an extensive palaeopathological examination was conducted, concentrating on dental alterations yielding information about diet, dental and skeletal conditions linked to the exposure to chronic stress as well as skeletal lesions used to infer information about activity and lifestyle. Due to the nature of the site and in consideration of the archaeological and historical evidence, identifying Säben-Sabiona as a burial ground of the ruling classes, which appears to have been stratified by rank as suggested by the variations of burial context and location, the sample was subdivided into an elite (n=107), i.e., graves within the church, inside a crypt and/or featuring wealthy material culture, and a non-elite group (n=78), i.e., burials outside the church with poor or no funerary goods.
The examined graves featured a minimum number of 226 individuals, which consisted of 94 males, 39 females, 54 subadults and 39 adults of not determinable sex. Based on the previously mentioned classification, 133 individuals were assigned to the elite group and 93 individuals to the non-elite group. In both subsamples, males were overrepresented. The lack of female burials for both subgroups further enforced the notion of a selective burial ground, whereby females appeared to have been interred elsewhere. Both subsamples displayed adaptations to the alpine environment, i.e., high levels of bone robusticity, and palaeopathological profiles consistent with a macronutrient rich diet, fairly frequent exposure to chronic stress and extremely physically demanding lifestyles. Even though osteological disorders were found in similar frequencies in both subgroups, thus, suggesting that social stratification was low, for almost all conditions the non-elite sample was more commonly and/or more severely affected.
This thesis provided novel insights into the demographic structure, diet and health of populations associated with early mediaeval Säben-Sabiona. Unique information about the composition of the Säben-Sabiona cemetery, which elucidates socio-cultural values and practices of populations residing in early mediaeval South Tyrol, was generated. The detailed palaeopathological analysis informs about health and living conditions of the people buried at this important site, in consideration of their social stratification. The combination of a thorough palaeodemographic and palaeopathological investigation in conjunction with an evaluation of funerary customs and materials provides a holistic interpretation, not only of the individual life history, but also the population as a whole. Thus, improves the contextualisation of the palaeochristian church at Säben-Sabiona and aids the understanding of early mediaeval social stratification. As for South Tyrol, standardised anthropological research concerning osteological samples is still in its very early stages, the present thesis provides a first step in supplying data, which can be used to establish normal osteological parameters, thus provides a solid foundation for future research
Repetitive periphere Magnetstimulation im Bereich der Nacken- und Schultermuskulatur als neuromodulatorische Intervention bei jungen Erwachsenen mit hochfrequenter episodischer Migräne
Get PDFMicrowave-shielded ultracold polar molecules
Get PDFSince the realization of Bose--Einstein condensates and degenerate Fermi gases, ultracold atoms with tunable interactions have become an essential platform for studying quantum many-body phenomena. Notable examples include the realization of BCS--BEC crossover and the simulation of the Bose/Fermi Hubbard model. Ultracold polar molecules could enrich the quantum gas toolbox with their long-range dipole-dipole interaction, which offers not only new opportunities in many-body physics, such as realizing the topological superfluid and the extended Hubbard model, but also applications in quantum chemistry, quantum computation, and precision measurements. However, the large number of internal degrees of freedom of molecules present a significant challenge in both cooling them to quantum degeneracy and controlling their interactions. Unlike atomic gases, a dense molecular sample suffers from fast collisional losses, preventing the implementation of evaporative cooling and the observation of scattering resonances. In this thesis, we describe how we solved the long-standing issue of collisional losses by microwave shielding, created a degenerate Fermi gas of NaK molecules, and discovered a new type of scattering resonances via which we created the first ultracold tetratomic molecules in the 100-nK regime.
By synchronizing the rotation of polar molecules with a circularly polarized microwave electric field, we equip the molecular sample with a highly tunable intermolecular potential. This not only stabilizes the gas against inelastic collisions but also enables field-linked scattering resonances for precise control over scattering lengths. At long range, the molecules interact via their induced rotating dipole moments. As they approach each other, their orientations realign to produce a repulsive force, thereby mitigating inelastic collisions at close distances. With an elastic-to-inelastic collision ratio of 500, we have achieved evaporative cooling of the molecular gas down to 21 nK and 0.36 times the Fermi temperature, setting a new record for the coldest polar molecular gas to date.
Thanks to the collisional stability of microwave-shielded molecules, we can directly load them into predominantly a single layer of a magic 3D optical lattice, achieving a peak filling fraction of 24%. These ultracold molecules, owing to their long lifetimes in their ground state and their long-range dipolar coupling, provide a unique platform to study quantum magnetism. With the achieved high filling fraction, we are prepared to study non-equilibrium spin dynamics such as rotational synchronization and spin squeezing.
We demonstrated that the interaction between microwave-shielded polar molecules is highly tunable via the microwave power, detuning, and polarization. When the interaction potential is deep enough to host field-linked bound states at the collisional threshold, a shape resonance is induced, allowing us to tune the scattering rate by three orders of magnitude. The field-linked resonances enables controls over the scattering length in a similar fashion as Feshbach resonance for ultracold atoms, promising the realization of strongly correlated phases, such as dipolar -wave superfluid. It also paves the way to investigate the interplay between short-range and long-range interactions in novel quantum matters, such as exotic supersolid.
Moreover, through a field-linked resonance, we associated for the first time weakly bound tetratomic molecules in the 100-nK regime, with a phase space density of 0.04. The transition from a Fermi gas of diatomic molecules to a Bose gas of tetratomic molecules paves the way for dipolar BCS--BEC crossover.
With microwave-shielded polar molecules, we have realized a quantum gas featuring highly tunable long-range interactions. The technique is universal to polar molecules with a sufficiently large dipole moment, and thus offers a general strategy for cooling and manipulating polar molecules, and for associating weakly bound ultracold polyatomic molecules. Utilizing the toolbox developed in ultracold atoms, this platform possesses the potential to unlock an entirely new realm of quantum simulation of many-body physics
Einfluss von Bayesian Reasoning auf die Diagnoserichtigkeit und -schnelligkeit bei Medizinstudierenden
Get PDFLong-term weight development in offspring exposed to obesity in pregnancy
Get PDFThe prevalence of childhood overweight has increased drastically, and weight development in preschool years is linked to future obesity. A greater risk of overweight at preschool age is conferred by a higher maternal preconception body mass index (BMI), an urgent public health issue, since overweight or obesity occurs in up to two-thirds of child-bearing women today, frequently developing metabolic complications. In fact, our research group previously found that women with obesity may develop dysglycemia towards the end of pregnancy, despite a negative test for gestational diabetes (GDM). Therefore, we hypothesized that late-pregnancy dysglycemia could also contribute to adverse longitudinal BMI development in their offspring. For prevention, such offspring should be identified at a time prior to the first upper divergence in BMI gain in the trajectory towards overweight manifestation. However, prediction of early deviations in weight gain has not been achieved on an individual level as a prerequisite for implementation in the public health setting, because data on weight trajectories in children who had exposure to gestational overnutrition and the contribution of “obesogenic influences” are lacking.
Using comprehensive and longitudinal data from different gestational and postnatal phases of the large Programming of Enhanced Adiposity Risk in CHildhood - Early Screening (PEACHES) cohort study of women with obesity and their children (n = 1,707), we performed linear mixed-effects models and mediation analysis to evaluate the long-term (from age 2 to 4 years) effect and contribution of obesity-related dysglycemia at the end of gestation (women’s HbA1c [glycated hemoglobin] at delivery ≥5.7%) on preschool BMI (at 4 years of age), respectively. We also identified specific patterns of BMI growth from birth until 5 years of age following exposure to obesity in pregnancy, assessed various BMI outcomes, and evaluated their underlying contributors in offspring using k-means cluster analysis and a series of multivariable regression models. Subsequently, a serial approach of individual risk score assessment, prediction, and re-assessments was developed using penalized logistic regressions. Data from an independent mother-child cohort (PErinatal Prevention of Obesity [PEPO], n = 11,730) were available for data validation.
In the analysis of children exposed to gestational obesity, a diagnosis of GDM did not influence offspring BMI at age 4 years. However, within the group of mothers with obesity who tested negative for GDM towards the end of the second trimester, dysglycemia in late pregnancy was associated with high BMI gains between ages 2 and 4 years in offspring (mean annual increment Δ 0.18, 95% confidence interval [CI] 0.06–0.30). Overall, it accounted for almost one-quarter of the contribution of gestational obesity on offspring BMI z-score at age 4 years. In these mothers, the presence of late-pregnancy dysglycemia was related to a risk of prediabetes or type 2 diabetes (T2D) a few years later that was four times higher than in mothers with normal HbA1c at delivery (relative risk [RR] 4.01, 95% CI 1.97–8.17). Excessive third-trimester weight gain was related to a mean increase in the risk of dysglycemia in late pregnancy by 72% (RR 1.72, 95% CI 1.12–2.65) in mothers with obesity who had a negative GDM test. Next, we focused on a “pre-symptomatic” offspring BMI outcome and identified a “high-risk” subgroup of children (21%) likely to undergo early upper divergence from a healthy BMI growth track after exposure to gestational overnutrition. Belonging to this upper BMI cluster was associated with a high risk of preschool overweight/obesity (odds ratio [OR] 16.13; 95% CI 9.98–26.05). Underlying pre- and perinatal influences such as high maternal weight gain (OR 2.08, 95% CI 1.25–3.45) and smoking in pregnancy (OR 1.94, 95% CI 1.27–2.95) were essential to predict a subsequent “higher-than-normal BMI growth” pattern in the 3-month-old, 1-year-old, and 2-year-old offspring. Sequential prediction models showed adequate predictive performances (area under the receiver operating characteristic [AUROC] 0.69–0.79, specificity 64.7–78.1%, sensitivity 70.7–76.0%), and findings were confirmed in the cohort PEPO.
In conclusion, in order to achieve healthy weight development at the beginning of life, efforts should be made to optimize maternal weight gain and glucose metabolism as well as fetal growth also in the 3rd trimester of pregnancy, particularly if the mother with obesity had a prior GDM-negative test result. After birth, children of women with obesity should be closely sequentially assessed for risk quantification and individual detection of an increased risk of “higher-than-normal” BMI growth at the established well-child care visits for intensified prevention measures. A “continuum” of targeted management strategies in the very early stages of life could help reduce intergenerational transmission of obesity
Designing intelligent support for learning from and in everyday contexts
Get PDFMotivation and engagement in learning benefit from a good match of learning settings and materials to individual learner contexts. This includes intrinsic context factors such as prior knowledge and personal interests but also extrinsic factors such as the current environment. Recent developments in adaptive and intelligent technology enable the personalisation of context-aware learning. For example, computer vision algorithms, machine translation, and Augmented Reality make it possible to support the creation of meaningful connections between learners and their context. However, for successful adoption in everyday life, these technologies also need to consider the learner experience.
This thesis investigates the design of personalised context-aware learning experiences through the lens of ubiquitous and self-directed language learning as a multi-faceted learning domain. Specifically, it presents and discusses the design, implementation, and evaluation of technology support for learning in and from learners’ everyday contexts with a strong focus on the learner perspective and user experience. The work is guided by four different roles that technology can take on in context-aware ubiquitous learning: For enhancing learning situations, it can (1) sense and (2) trigger in learners’ everyday contexts. For enhancing learning contents, it can (3) augment activities and (4) generate learning material from learner everyday contexts.
With regards to the sensing role, the thesis investigates how learners typically use mobile learning apps in everyday contexts. Activity and context logging, combined with experience sampling, confirm that mobile learning sessions spread across the day and occur in different settings. However, they are typically short and frequently interrupted. This indicates that learners may benefit from better integrating learning into everyday contexts, e.g. by supporting task resumption.
Subsequently, we explore how this integration could be supported with intelligent triggers linked to opportune moments for learning. We conceptualise and evaluate different trigger types based on interaction patterns and context detection. Our findings show that simple interactions (e.g. plugging in headphones) are promising for capturing both availability and willingness to engage in a learning activity. We discuss how similar interaction triggers could be adapted to match individual habits.
In the area of enhancing learning contents, we first investigate how enjoyable everyday activities could be augmented for learning without disrupting these activities. Specifically, we assess the learner experience with interactive grammar support in e-readers and adapted captions for audio-visual media. Participants in our studies felt that the learning augmentations successfully supported their learning process. The information load of the learning support should match the learners’ current needs to maintain the activity flow. Learners may need encouragement to opt for novel concepts optimised for learning (e.g. time-synchronised captions) rather than sticking to habits (e.g. standard captions).
Next, the thesis explores learner needs and preferences in generating their own personalised learning material from their context. We design and evaluate automated content generation methods that generate learning opportunities from objects in the learner’s environment. The connection to the learner’s context is established with state-of-the-art technology, such as object detection and Augmented Reality. Through several user studies, we show that learning performance and engagement with auto-generated personalised learning material is comparable to predefined and manually generated content. Findings further indicate that the success of personalisation depends on the effort required to generate content and whether the generation results match the learner’s expectations.
Through the different perspectives examined in this thesis, we provide new insights into challenges and opportunities that we synthesise in a framework for context-aware ubiquitous learning technology. The findings also have more general implications for the interaction design of personalised and context-aware intelligent systems. Notably, for the auto-generation of personalised content, it is essential to consider not only correctness from a technological perspective but also how users may perceive the results.Lernmotivation und Engagement profitieren davon, wenn Lernumgebungen und Lernmaterialien auf den individuellen Kontext der Lernenden abgestimmt sind. Dieser umfasst sowohl intrinsische Faktoren wie Vorkenntnisse und persönliche Interessen, aber auch extrinsische Faktoren wie die aktuelle Umgebung. Aktuelle Weiterentwicklungen im Bereich adaptiver und intelligenter Technologien ermöglichen es, Lernen kontextbewusst zu personalisieren. So können mithilfe von Computer-Vision-Algorithmen, maschineller Übersetzung und Augmented Reality sinnvolle Verknüpfungen zwischen Lernenden und ihrem Kontext geschaffen werden. Allerdings müssen diese Technologien für einen erfolgreichen Einsatz im Alltag auch die Lernerfahrung mit einbeziehen.
Diese Arbeit untersucht die Gestaltung personalisierter kontextbewusster Lernerfahrungen aus der Perspektive des ubiquitären und self-directed Learning im Sprachenlernen, einem vielseitigen Lernbereich. Insbesondere wird die Konzeption, Implementierung und Evaluierung von Technologieunterstützung für das Sprachenlernen in und aus dem Alltagskontext der Lernenden vorgestellt und diskutiert, wobei der Schwerpunkt auf der Perspektive der Lernenden und der Nutzererfahrung liegt. Die Arbeit orientiert sich an vier verschiedenen Rollen, die Technologie im kontextbewussten Lernen einnehmen kann. Um Lernsituationen anzureichern, kann Technologie im Alltagskontext von Lernenden (1) erfassen und (2) auslösen. Um Lerninhalte anzureichern, kann Technologie aus dem Alltagskontext (3) Aktivitäten augmentieren und (4) Inhalte generieren.
Im Hinblick auf die erfassende Rolle von Technologie wird in dieser Arbeit untersucht, wie die Lernenden mobile Lern-Apps in alltäglichen Kontexten nutzen. Die Aufzeichnung von Aktivitäten und Kontexten in Kombination mit Experience Sampling bestätigt, dass Lerneinheiten im mobilen Lernen über den Tag verteilt sind und in verschiedenen Umgebungen stattfinden. Allerdings sind sie in der Regel kurz und werden häufig unterbrochen. Dies deutet darauf hin, dass die Lernenden von einer besseren Integration des Lernens in ihren Alltagskontext profitieren könnten, z. B. durch Unterstützung des Wiedereinstiegs nach einer Unterbrechung.
Anschließend untersuchen wir, wie diese Integration durch intelligente Trigger unterstützt werden könnte, die mit passenden Lernzeitpunkten verknüpft sind. Wir konzipieren und evaluieren verschiedene Arten von Triggern auf Basis von Interaktionsmustern und Kontexterkennung. Unsere Ergebnisse zeigen, dass einfache Interaktionen (z. B. das Einstecken von Kopfhörern) vielversprechend dafür sind, sowohl die Verfügbarkeit als auch die Bereitschaft für eine Lernaktivität zu erfassen. Wir diskutieren, wie ähnliche Interaktionstrigger an individuelle Gewohnheiten angepasst werden können.
Im Bereich der Augmentierung von Lerninhalten untersuchen wir zunächst, wie unterhaltsame Alltagsaktivitäten für das Lernen aufbereitet werden können, ohne diese Aktivitäten zu beeinträchtigen. Konkret bewerten wir die Lernerfahrung mit interaktiver Grammatikunterstützung in E-Readern und angepassten Untertiteln für audiovisuelle Medien. Die Teilnehmer:innen unserer Studien fanden, dass die Lernunterstützung ihren Lernprozess erfolgreich förderte. Die Informationslast im Lernsystem sollte auf die aktuellen Bedürfnisse der Lernenden angepasst werden, damit das Flow-Erlebnis nicht beeinträchtigt wird. Die Lernenden brauchen möglicherweise Ermutigung dafür, sich für neuartige, lernoptimierte Konzepte zu entscheiden (z. B. zeitsynchrone Untertitel), anstatt an Gewohnheiten festzuhalten (z. B. Standarduntertitel).
Als Nächstes werden in dieser Arbeit die Bedürfnisse und Präferenzen der Lernenden bei der Erstellung ihres eigenen personalisierten Lernmaterials aus ihrem Kontext untersucht. Insbesondere werden Methoden zur automatischen Generierung von Inhalten entwickelt und evaluiert, die Lernmöglichkeiten aus Objekten in der Umgebung des Lernenden generieren. Die Verbindung zum Kontext des Lernenden wird durch aktuelle Technologien wie Objekterkennung und Augmented Reality hergestellt. Wir zeigen anhand mehrerer Nutzerstudien, dass die Lernleistung und das Engagement bei automatisch personalisiertem Lernmaterial mit vordefinierten und manuell erstellten Inhalten vergleichbar sind. Die Ergebnisse zeigen außerdem, dass der Erfolg der Personalisierung vom Aufwand abhängt, der für die Erstellung der Inhalte erforderlich ist, und davon, ob die generierten Materialien den Erwartungen der Lernenden entsprechen.
Die verschiedenen Perspektiven, die in dieser Arbeit untersucht werden, bieten neue Einblicke in Herausforderungen und Möglichkeiten, die wir in einem Framework für kontextbewusste ubiquitäre Lerntechnologie zusammenfassen. Die Ergebnisse haben auch allgemeinere Auswirkungen auf die Gestaltung der Interaktion mit personalisierten und kontextbewussten intelligenten Systemen. Beispielsweise ist es bei der automatischen Generierung personalisierter Inhalte wichtig, nicht nur die Korrektheit aus technologischer Sicht zu berücksichtigen, sondern auch, wie die Nutzer die Ergebnisse wahrnehmen
Anwendung der peripheren elektrischen Stimulation bei Gesunden und Schlaganfallpatienten und die Auswirkungen auf die somatosensorisch evozierten Potenziale
Get PDFNur wenige Studien haben die somatosensorisch evozierte Potenziale (SEP) genutzt, um die kortikale Neuroplastizität und die Rehabilitationsprognose bei Schlaganfallpatienten nach der Anwendung der funktionellen Elektrostimulation (FES) zu untersuchen. Das Hauptziel meiner Studie war es, systematisch zu überprüfen, ob FES eine Rolle bei der Veränderung der Latenzen und Amplituden von SEPs bei gesunden Probanden oder bei den Patienten nach einem Schlaganfall darstellt. Weiterhin suchte ich nach einer Korrelation zwischen sensorischen und motorischen Funktionstests und den Veränderungen der SEP-Latenzen und Amplituden. Folgende Datenbanken wurden durch-sucht: Pubmed/MEDLINE, Scopus/ScienceDirect, Web of Science/Clarivate, Cochrane Library, The Physiotherapy Evidence Database (PEDro), und Clini-calTrials.gov. Die Titel und Abstracts sowie die Volltexte der Studien wurden von zwei unabhängigen Autoren anhand von im Vorfeld festgelegten Kriterien auf ihre Eignung geprüft. Es wurden alle Studien, die sich auf die Behandlung der oberen oder unteren Extremitäten oder des Rumpfes mit FES, inkludiert. Die systematische Suche resultierte in insgesamt 11344 Studien, von denen nur 10 evaluiert wurden. Ich konnte keinen ausreichenden Nachweis finden, dass das SEP als Indikator für eine Prognose der Rehabilitation nach einem Schlaganfall nützlich ist. Ich fand jedoch einen Zusammenhang zwischen verschiedenen sensorischen und motorischen Funktionsbewertungen und Veränderungen der SEP-Komponenten. Die Schlaganfallstudien mit FES, die eine willkürliche Kontraktion für eine bestimmte Bewegung oder Aufgabe initiieren, deuten auf eine positive Beziehung und Korrelation mit den Bewertungen der motorischen Funktion hin. Es könnte darauf hinweisen, dass FES eine positive Auswirkung auf die sensorische Reorganisation hat, was sich in der Veränderung der SEP-Amplitude und -Latenz widerspiegelt. Das Ausmaß der Konnektivität zwischen SEP und kortikaler Plastizität lässt sich bisher nicht feststellen. Um diese Hypothese zu bestätigen, haben wir ein randomisiertes, kontrolliertes zwei-Perioden-Crossover-Design mit gesunden Probanden und Schlaganfallpatienten durchgeführt. Meine zweite Studie analysierte Veränderungen der pathologischen SEP-Latenzen und Amplituden nach einem akuten Schlaganfall nach zweiwöchiger Rehabilitation mit FES. Die Veränderungen der SEPs wurden auch mit der FES-Intervention bei Schlaganfall-Symptomen der Fußheberschwäche (FHS) korreliert, die anhand des 10-Meter-Gehtests und der Stärke der Dorsalflexion im Fußgelenk bewertet wurden. Gruppe A erhielt die FES direkt, während Gruppe B nach zwei Wochen behandelt wurde. Zudem wurden in der unbehandelten Kontrollgruppe gesunder Erwachsener in den gleichen Zeitabständen wie bei den Schlaganfallpatienten wiederholte SEP-Messungen durchgeführt. Die statistische Analyse (ANOVA) zeigte eine signifikante Abnahme der SEP-Latenzen des paretischen Nervus tibialis (NT) in den Schlaganfallgruppen nach der Intervention, gefolgt von einer Abnahme der SEP des nicht-paretischen NT im Vergleich zur Kontrollgruppe der gesunden Erwachsenen. Darüber hinaus wurde in den Schlaganfallgruppen eine Zunahme der Kraft des FHS und eine Verringerung der Kadenz beobachtet. Wir fanden eine moderate Korrelation (r=0,50-0,70) zwischen der Latenzzeit des nicht-paretischen NT und der Schrittkadenz in den Schlaganfallgruppen nach der FES-Zeit. Der pathologische Gang wurde verändert und das afferente SEP-Feedback verbesserte sich nach der FES-Intervention.A small number of studies used somatosensory evoked potentials (SEP) to demonstrate changes in cortical sensory function in healthy subjects or to assess cortical plasticity and rehabilitation prognosis in stroke patients following an functional electrical stimulation (FES) intervention. The main objective of first study was to systematically investigate whether FES is involved in altering SEP latency and amplitude in healthy subjects and stroke survivors. We also searched for correlations between sensory and motor assessments and SEP component changes in the included studies. Databases of interest were: Sco-pus (ScienceDirect), Pubmed (MEDLINE), Web of Science, The Physiotherapy Evidence Database (PEDro), Cochrane Library, and ClinicalTrials.gov. A priori eligibility criteria were used to screen titles, abstracts, and reports for eligibility. There were no limitations regarding the treatment of the upper extremity, lower extremity, or trunk with FES. The last systematic search resulted in 11344 entries. However, only ten of these were evaluated. There was insufficient evidence for using SEP to predict rehabilitation prognosis after stroke. However, we did find a correlation linking the assessment of sensory and motor function and the changes in the components of the SEPs. Moreover, a positive relationship and correlation with motor function assessments in stroke studies using FES, which initiates a voluntary contraction used for a specific movement or task, was found. However, the degree of connectivity between the SEP and cortical plasticity remains elusive. To confirm this hypothesis, we conducted a randomised, controlled, two-period crossover study with stroke patients and healthy volunteers. The second study examined changes in pathological SEP latencies and amplitudes following an acute stroke after two weeks of rehabilitation with FES. Changes in SEPs between the stroke groups were also correlated with FES therapy intervention for foot drop stroke symptoms, assessed by the 10-metre walk test and strength of dorsal flexion in the foot ankle. Group A received the FES directly, while group B was treated after two weeks. Moreover, repeated SEP measurements were evaluated in the untreated control group of healthy adults at the same interval as for stroke groups. The statistical measures (ANOVA) showed a significance decrease in paretic tibial nerve SEP latencies in stroke groups after the intervention, tracked by a decrease in non-paretic tibial nerve SEP comparing to the control group of healthy adults. Furthermore, increasing of foot drop strength and reducing the cadence in stroke groups was found. We found a moderate correlation (r=0.50-0.70) between non-paretic tibial nerve latency N50 and step cadence in stroke groups after the FES time. The pathological gait was modified with improved SEP afferent feedback following the FES intervention
The influence of coagulation system on early leukocyte recruitment and acute microcirculatory injury after extended hepatectomy
Get PDFDas hepatektomie-induzierte Leberversagen ist ein potentiell tödliches Krankheitsbild nach erweiterter Leberresektion oder Leberteiltransplantation. Dieses Versagen scheint einerseits durch eine supraphysiologische Belastung der Restleber, andererseits durch die hyperperfusionsbedingten Mikrozirkulationsverletzungen und eine verhinderte Leberregeneration verursacht zu werden. Der genaue pathophysiologische Mechanismus der mikrovaskulären Schädigung in der akuten Phase konnte jedoch bisher noch nicht entschlüsselt werden.
Im Rahmen der vorliegenden Doktorarbeit wurden die Einflüsse der wichtigen Bestandteile der Koagulationskaskade bei akuter Leberschädigung nach partieller Hepatektomie mittels intravitalmikroskopischer Methoden sowie weiterführender laborchemischer Untersuchungen und (immun-)histochemischer Aufarbeitung der Leberpräparate untersucht.
Zuerst wurde ein Mausmodell für die intravitalmikroskopische Untersuchung etabliert. Nach erweiterter Hepatektomie wurde neben einer Perfusionsstörung eine ausgeprägte Endothel- Leukozyten-Interaktion beobachtet. Die Serinproteasen beeinflussten sowohl die Mikroperfusion wie auch die Leberschädigung durch eine frühe Leukozytenrekrutierung nach partieller Hepatektomie.
Mittels eines Thrombozytendepletionsmodells wurde der Einfluss der Thrombozyten nach erweiterter Hepatektomie untersucht. Die Ergebnisse deuteten darauf hin, dass Thrombozyten die Rekrutierung der verschiedenen Leukozytensubpopulationen durch eine ICAM-1-abhängige Endothel-Leukozyten-Interaktion regulierten. Zudem führte die Depletion der Thrombozyten zu einer signifikant verminderten Verschlechterung der Leberfunktion.
Infolgedessen wurde die Rolle des PAR-4, ein Aktivator der Thrombozyten, in der Bildung von Mikrothrombosen als Ursache der Perfusionsstörung nach partieller Hepatektomie mithilfe der Zwei-Photon-Mikroskopie untersucht. Die Thrombozytenaktivierung über PAR-4 induzierte Mikrothrombosen und vermehrte Neutrophil-Thrombozyten-Interaktionen in hepatischen Sinusoiden, wodurch eine Akutleberschädigung nach partieller Hepatektomie verschlimmert wurde.
Schlussendlich wurde die Fibrinogenbindung am hepatischen Endothel nach partieller Hepatektomie beobachtet. Die deutliche Ablagerung des Fibrinogens in der Lebermikrozirkulation bewies eine Aktivierung und Beanspruchung des Koagulationssystems unter einem stark gesteigerten Scherstress unmittelbar nach der Leberresektion.
In dieser Studie wurde der Pathomechanismus des Leberversagens nach Hepatektomie mit Hilfe der in-vivo-Mikroskopie und verschiedener Mausmodelle innovativ untersucht. Dies war auch die erste Beschreibung einer intravitalen Zwei-Photonen-Mikroskopie-Studie im Zusammenhang mit dem hepatektomie-induzierten Leberversagen. Die klinische Relevanz der vorgestellten Komponenten der Koagulationskaskade für therapeutische Interventionen bleibt in weiterführenden Studien zu überprüfen.Post-hepatectomy liver failure or Small-for-size syndrome is a potentially fatal complication after extended liver resection or partial liver transplantation. This is caused by supraphysiologic perfusion in the remnant liver and microcirculatory injury. However, the exact pathophysiological mechanism of microvascular injury in the acute phase is still unclear.
In the present work, the impact of important components from the coagulation cascade was investigated in acute liver injury after partial hepatectomy.
First, a mouse model suitable for intravital microscopic examination was established. After extended hepatectomy, an increased endothelial-leukocyte interaction was observed in addition to perfusion failure. Serine proteases affected both microperfusion and liver injury by inducing early leukocyte recruitment after partial hepatectomy.
A platelet depletion model was used to investigate the influence of platelets after extended hepatectomy. The results indicated that platelets regulated the recruitment of different leukocyte subpopulations through an ICAM-1-dependent pattern. In addition, the platelet depletion resulted in significantly improved liver function.
Furtherly, the role of PAR-4, an activator of platelets, was investigated using two-photon microscopy. Platelet activation via PAR-4 induced microthrombosis and increased neutrophil- platelet interactions in hepatic sinusoids, exacerbating acute liver injury after partial hepatectomy.
Finally, fibrinogen deposition to hepatic endothelium after partial hepatectomy was investigated. The deposition of fibrinogen in the liver microcirculation reflected the activation of the coagulation system under increased shear stress immediately after liver resection.
In this study, the pathomechanism of post-hepatectomy liver failure was innovatively investigated by utilizing in vivo microscopy and different murine models. This was also the first description of in vivo two-photon microscopy study in the context of post-hepatectomy liver failure. The clinical relevance of the presented components of the coagulation cascade as therapeutic interventions remains to be verified in further studies
