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Implementation and Evaluation of Antimicrobial Resistance Surveillance Systems in Sub-Saharan Africa
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The thesis aims to enhance the understanding of antimicrobial resistance (AMR) patterns in Sub-Saharan Africa and evaluate existing laboratory capacities for AMR surveillance in the region. It comprises two comprehensive cross-sectional studies. The first, conducted between November 2013 and March 2017, analyses clinical specimens from febrile patients hospitalized in Burkina Faso, Gabon, Ghana, and Tanzania, with focus on key AMR concerns highlighted by the World Health Organization, including carbapenem-resistant and extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, fluoroquinolone-resistant Salmonella enterica, and methicillin-resistant Staphylococcus aureus. Notable variations in susceptibility patterns were found, with Burkina Faso exhibiting high prevalence in ESBL production and ciprofloxacin resistance, emphasizing the importance of region-specific AMR surveillance and improved reporting for targeted interventions. The study found no resistance to carbapenems, indicating their potential as an effective option against infections caused by ESBL-producing bacteria, despite their cost and limited availability. However, the thesis advocates for sustained vigilance in detecting emerging carbapenemase-producing pathogens to ensure timely response and management.
Paper two assessed a convenience sample of healthcare facilities in Kenya, encompassing public and private sectors, rural and urban settings, as well as national, county and community units. The assessment was conducted through online surveys of laboratory managers between October 5th and 8th, 2020, with the aim of evaluating laboratory capacity for AMR surveillance and identifying areas for improvement. A scoring scheme was applied to evaluate indicators of quality assurance, management and dissemination of AMR data, material and equipment, staffing, microbiology competency, biosafety and certification. Gaps in laboratory information management technology, quality assurance, data management, and resources were identified, especially in rural areas. Interestingly, facilities performing bacterial cultures only and those conducting antimicrobial susceptibility testing (AST) were found to have similar capacities, except in terms of equipment. This implies that investing in equipment could enhance the capabilities of facilities conducting cultures only to also perform ASTs, presenting a noteworthy opportunity for expanding AMR diagnostics and improving healthcare delivery within Kenya and potentially beyond its borders.
The thesis advances AMR knowledge in Sub-Saharan Africa, providing a roadmap for tailored policies, strengthened surveillance systems, and improved capacities in health laboratories. The findings can serve as a basis to gauge potential impacts of future interventions and the applied scoring tool can be utilized in similar contexts. Furthermore, the evaluation tool in the current research stands as a valuable resource for facilities to independently assess their capacities and practices, contributing to ongoing development efforts in combating AMR.ABSTRACT
Aim: To enhance the understanding of antimicrobial resistance patterns in Sub-Saharan Africa and evaluate existing laboratory capacity for AMR surveillance in the region.
Methods: The thesis comprises two cross-sectional studies: a quantitative approach in [I] and a mixed methods approach in [II]. In Paper I, clinical specimens were collected from febrile patients aged ≥30 days and ≤15 years in Burkina Faso, Gabon, Ghana, and Tanzania. Antimicrobial susceptibility testing was performed on Enterobacterales and Staphylococcus aureus using the disk diffusion method. ESBL production was confirmed via a double-disk diffusion test and gene detection. Multilocus sequence typing was conducted on ESBL-producing Escherichia coli, Klebsiella pneumoniae, ciprofloxacin-resistant Salmonella enterica, and Staphylococcus aureus. Ciprofloxacin-resistant Salmonella enterica isolates were screened for plasmid-mediated resistance genes and mutations. S. aureus isolates were tested for mecA and Panton-Valentine Leukocidin (PVL) presence and spa-typed. In Paper II, health facilities in Kenya were conveniently sampled. Online surveys were conducted with laboratory managers to assess quality assurance, data management, resources, staffing, competency, biosafety, and certification. Facility capacities were evaluated using a 0-1 scoring scheme and compared across facility types, settings, and governance levels.
Results: The study analyzed 4,052 specimens from 3,012 patients, finding 219 positive cultures. Prevalence of ESBL-producing Enterobacterales varied: highest in Burkina Faso (45.2%), followed by Gabon (25.8%) and Ghana (15.1%), while Tanzania had none. ESBL-positive Salmonella was found in Burkina Faso and methicillin-resistant S. aureus in Ghana. ST131 dominated ESBL E. coli, and ESBL K. pneumoniae had diverse sequence types. Ciprofloxacin-resistant Salmonella were common in Burkina Faso (50%), carrying qnrB genes. PVL was found in 81.3% of S. aureus (I). Among 219 participating facilities, most did not offer bacterial culture testing (n= 135, 61.6%), while 47 (21.5%) provided culture services only, and 37 (16.9%) conducted antimicrobial susceptibility testing (AST). Major gaps in AST facilities were poor access to laboratory information management technology (LIMT) (score: 45.9%) and low participation in external quality assessment (EQA) programs (score of 67.7%). Urban facilities had more than two-fold higher access to laboratory technology compared to rural facilities (58.6% vs. 25.0%). Laboratories lacking culture services showed significant infrastructural gaps (average score 59.4%), whereas facilities performing cultures only and AST had notably high and similar scores (Average scores: 83.6%. & 82.9%). Lack of equipment was the main challenge for susceptibility testing in 46.8% of laboratories (II).
Conclusions: The findings highlight distinct susceptibility patterns in the study regions and underscore the need for local AMR surveillance and reporting. The study also identified gaps in laboratory information management technology, external quality assurance, and equipment in the surveyed health facilities in Kenya. The findings suggest that by investing in equipment, facilities performing cultures can be successfully upgraded to provide additional antimicrobial susceptibility testing, presenting a chance for a leap toward improved AMR diagnostics and surveillance in the country
Shaping the Future: Surface-Modified Cellulose Nanofibrils (CNFs) for Multifunctional 3D-Printable Hybrid Materials
Get PDFCellulose nanofibrils (CNFs) are well-known biodegradable, renewable, and biocompatible materials that can be extracted from lignocellulosic materials via various chemical, mechanical, or enzymatic processes. Typically, CNFs obtained by mechanical processes are in aqueous media, generating viscous dispersion. The abundant numbers of hydroxy groups on their surface are a double-edged sword when utilizing CNFs: while those functions lead to some drawbacks such as hygroscopic character, instability in many organic solvents, strong interfibrillar hydrogen interactions (leading to fibril aggregation), they can also participate in many chemical modifications through specific reactions.
This thesis presents a surface modification pathway for CNFs, beginning with their conversion into CNF-based macroinitiators (CNF-MI) in a single step, followed by a Cu0-mediated radical polymerization (SET-LRP) to graft polymers onto the CNF surface. The introduction of polymers onto their surface allows to change the properties and the behavior of the CNF drastically. By carefully selecting the appropriate monomers, CNF can be adapted and is suitable for many applications
Der Einfluss von epithelialem HMGB1 auf Entzündungsprozesse im murinen Darm
No full textDas Darmepithel spielt eine entscheidende Rolle bei der Aufrechterhaltung der Funktion und Integrität des Darms. Es dient als physische Barriere zwischen dem Inhalt des Lumens und dem darunter liegenden Gewebe. Gleichzeitig ist es an der Nährstoffaufnahme und der Immunantwort beteiligt. Zelleigene Alarmine, die auch als damage-associated molecular patterns (DAMPs) bezeichnet werden, und pathogen assoziierte Strukturmotive, pathogen-associated molecular patterns (PAMPs), treffen hier aufeinander. Eine effiziente Wundheilung und die Induktion von Entzündungsreaktionen bei Störungen der Homöostase oder Gewebsschädigungen der Darmbarriere sind für den Organismus lebensnotwendig. Ein Schlüsselmolekül, das an der Entzündungsreaktion während einer Schädigung oder Entzündung des Darmepithels beteiligt ist, ist High-mobility group box 1 (HMGB1). In den letzten Jahren wurde dieses Protein zunehmend als wichtiger Faktor in der Pathogenese von chronisch entzündlichen Darmerkrankungen (CED) sowie Darmkrebs beschrieben. HMGB1 wird sowohl während entzündlicher Darmerkrankungen als auch in Darmkrebsgewebe überexprimiert. Zudem korreliert die HMGB1-Konzentration in Serum und Stuhl von CED-Patienten mit einem erhöhten Schweregrad der Erkrankung.
In Vorarbeiten zu diesem Projekt konnte bereits gezeigt werden, dass eine genetische HMGB1-Defizienz in Darmepithelzellen den Krankheitsverlauf bei der chemisch induzierten DSS-Colitis der Maus signifikant verschlechtert, während diese keine Auswirkungen im Rahmen der bakteriellen C.rodentium oder chronischen T-Zell-induzierten Kolitis hat. Im Modell der spontanen Karzinogenese führte die epitheliale HMGB1-Deletion jedoch zu einer verstärkten Tumorbildung. In dieser Arbeit wurde primär die kontextabhängige Funktion von epithelialem HMGB1 im DSS-geschädigten Darm untersucht, um die Reaktionen des Wirtes auf Darmverletzungen besser zu charakterisieren und potenziell eine Grundlage für weitere Therapieansätze zu schaffen.
Zusammenfassend konnte gezeigt werden, dass eine genetische epitheliale HMGB1-Defizienz keinen Einfluss auf die Funktionalität sowie die Proliferation und Migrationskapazität des Epithels in der frühen Phase der DSS-Colitis hat. Dies konnte durch BrdU- und Ki-67-Färbungen sowie durch Scratch-Assays verdeutlicht werden. Eine DSS-induzierte Entzündung an Organoiden in vitro führte zu einer vergleichbaren Induktion von Genen, die an der Entzündung beteiligt sind, sowie einem unveränderten Wachstumsverhalten. Dies weist auf eine unveränderte zelluläre Grundfunktionalität und Reaktionsfähigkeit in Abwesenheit von intrazellulärem HMGB1 hin. Die Integrität der Darmbarriere wird durch eine epitheliale HMGB1-Defizienz nicht beeinträchtigt. Dies konnte durch einen vergleichbaren Anstieg der Permeabilitätsmarker IFABP, DAO und Zonulin im Serum nach 7 Tagen DSS-Behandlung gezeigt werden. Weiterhin war das Genexpressionsniveau von tight junctions zwischen Hmgb1ΔIEC und Hmgb1f/f vergleichbar, was auf vergleichbare Barriereeigenschaften bei Abwesenheit von epithelialem HMGB1 hindeutet. Die Analyse der epithelialen Sequenzierungsdaten zeigte eine stark abweichende Programmierung der Epithelzellen und in einem geringeren Maße eine transkriptionelle Veränderung der myeloiden Immunzellen in Hmgb1ΔIEC in der frühen Phase der DSS-Colitis. Die Reprogrammierung der Epithelzellen ist durch Veränderungen von Signalwegen charakterisiert, die mit dem Umbau der extrazellulären Matrix und ihrer Organisation assoziiert sind, was sich in einer veränderten Wundheilung oder einer veränderten Zell-Zell-Verbindung bei der Heilung der Läsionen ausdrücken könnte. Die veränderte Signalgebung an Epithelzellen und myeloiden Zellen steht vermutlich in Zusammenhang mit der Signalwirkung durch weitere PAMPs wie Lipopolysaccharid und anderen Pathogenen im Rahmen der Colitis
Exekutive Kontrolle Emotionaler Gesichtsausdrücke
Get PDFAutomated assessment with computer software offers new, efficient opportunities for measurement of facial expressions of emotion. However, little is known about reliability and validity of these assessment tools.
In Publication 1, we investigated the quality of a machine vision algorithm (FACET, iMotions, 2016) using standardized databases of dynamic facial expressions under various conditions (angle, distance, lighting, and resolution). We found high reliability in ratings concordance for facial expressions and went on examining the convergent validity of automated assessment and electromyography (EMG) by measuring reaction times (RTs) during the production of joy and anger expressions in a response priming task. Both EMG and automated assessment data showed similar performance costs in RTs when inhibiting an incorrectly prepared expression and reprogramming the correct one. These results support the use of automated assessment for evaluating experimental effects in facial expressions.
In Publication 2, we combined electroencephalography (EEG) and automated facial expression assessment, for the first time. We started examining facial expressions of joy, fear, and disgust in response to different visual stimuli using a go/no-go task. Then we went on focusing on expressions of joy and disgust influenced by gaze direction (with and without eye contact) in a more natural setting with a real person as the stimulus. Analysis of RTs, errors, and an event related potential (ERP) analysis of the no-go P3 suggest that facial expressions modulated by mimicry, emotional reactions, and push factors require greater top-down control, especially for expressions of joy compared to fear and disgust.
In Publication 3, we examine the demands of a social situation using a Stroop-like task. Participants took part in a simulated online dating scenario to study possible moderation effects FACIAL EXPRESSION OF EMOTION 6 of perceived attractiveness on facial expressions. RTs showed facilitation for deliberate expressions of joy and disgust with congruent pictures, but interference from incongruent expressions only affected joy. Accuracy decreased when participants expressed disgust at a smiling, attractive stimulus, without affecting RTs. ERP data revealed an early posterior negativity (EPN) for better sensory processing of joy over neutral expressions and a more negative N2 indicating conflict detection from mismatched expressions. Our findings demonstrate automatic tendencies to imitate facial expressions of joy and disgust.
Across all experiments, we successfully utilized and demonstrated the benefits of an automated assessment technique for investigating the executive control of facial expressions. However, the lack of process theory of emotion and the experimental study designs, with their numerous trial repetitions, suggest a lack of construct validity, raising doubts about the involvement of emotions in the observed effects.
Keywords: Facial action coding system, Automated facial expression recognition, Reliability, Validity, Executive functions, Top-down control, Go/no-go task, Emotional expression interference, Facial mimicr
Search for pair production of heavy particles decaying to a top quark and a gluon and development of ML-based L1 trigger strategies at the CMS experiment
Get PDFIn this thesis, I present a search for a potential signature of new physics: the existence of a new resonance t*, characterized by its decay into a top quark and a gluon. I use 138 fb^{-1} of proton-proton collision events gathered with the Compact Muon Solenoid (CMS) experiment at the Large Hadron Collider (LHC). I analyze events with a single lepton, multiple jets, and missing transverse momentum and enrich potential signal events using a deep neural network (DNN). I utilize an an active, two-step decorrelation procedure to ensure that the DNN is independent of the sensitive variable ST of the search. This variable is defined as a scalar energy sum of all considered objects. I analyze distributions of ST in search for pair production of t* with either spin-1/2 or spin-3/2. The results agree with Standard Model predictions. Therefore, I set exclusion limits on the production cross section of t*. In the spin-1/2 case, these are between 120 fb for m_{t*} = 700 GeV and 0.8 fb for m_{t*} = 3000 GeV. For t* with spin-3/2 , the exclusion limits are between 15 fb for m_{t*} = 700 GeV and 1.0 fb for m_{t*} = 2750 GeV. Assuming all t* decay as t -> tg, I exclude the existence of t* below a mass of 1050 GeV for spin-1/2 and 1700 GeV for spin-3/2. These are the most stringent exclusion limits for this particle to date. In a second part, I present the development of algorithms for the Level-1 trigger (L1T) of CMS, which utilize machine learning to improve on currently used algorithms. Due to the high collision rate in CMS and the resulting immense data streams, the L1T needs to decide whether to store or discard an event at a rate of 40 MHz. Especially towards the high-luminosity phase of the LHC, novel techniques will be crucial for CMS to ensure optimal performance of the trigger system. I present studies on the optimization, hardware integration and usage of a trigger based on a neural network. I show that events of a HH -> bbWW (single muon) process can be selected more effectively than with classical algorithms using a lightweight neural network. I demonstrate that this network can be integrated into the hardware of the CMS L1T.In dieser Arbeit präsentiere ich eine Suche nach einer potentiellen Signatur neuer Physik: der Existenz einer Resonanz t*, die in ein Top-Quark und ein Gluon zerfällt. Ich verwende 138 fb^{-1} an Daten von Proton-Proton Kollisionen, die mit dem Compact Muon Solenoid (CMS) Detektor am Large Hadron Collider (LHC) gemessen wurden. Ich analysiere Ereignisse mit einem Lepton, Jets und fehlendem transversalen Impuls und reichere potentielle Signal-Ereignisse mithilfe eines Deep Neural Networks (DNN) an. Ich nutze eine aktive, zweistufige Dekorrelationsprozedur um sicherzustellen, dass das DNN unabhängig von der sensitiven Variable ST der Suche ist. Diese ist als skalare Impulssumme aller betrachteten Objekte definiert. Ich analysiere ST-Verteilungen auf der Suche nach Paarproduktion von t* mit Spin-1/2 oder Spin-3/2. Meine Resultate stimmen mit den Vorhersagen des Standardmodelles überein, so kann ich die Paarproduktion von t* mit Spin-1/2 , je nach Masse des t*, für Wirkungsquerschnitte zwischen 120 fb für m_{t*} = 700 GeV und 0.8 fb für m_{t*} = 3000 GeV ausschließen. Für ein t* mit Spin-3/2 liegen die Ausschlussgrenzen zwischen 15 fb für m_{t*} = 700 GeV und 1.0 fb für m_{t*} = 2750 GeV. Unter der Annahme, dass alle t* als t* -> tg zerfallen, kann die Existenz eines t* unterhalb einer Masse von 1050 GeV für Spin-1/2 bzw. 1700 GeV für Spin-3/2 ausgeschlossen werden. Dies sind die bisher stringentesten Ausschlussgrenzen für dieses Teilchen. In einem zweiten Teil präsentiere ich die Entwicklung von Algorithmen für den Level-1 Trigger (L1T) von CMS, die mithilfe von maschinellem Lernen versuchen
eine Verbesserung gegenüber aktuellen Algorithmen zu erzielen. Aufgrund der hohen Kollisionsrate in CMS und den daraus resultierenden immensen Datenströmen muss der L1T mit einer Rate von 40 MHz entscheiden, ob ein Ereignis gespeichert wird. Insbesondere in Hinblick auf die zukünftige ”High-Luminosity”-Phase des LHC sind solche neuartigen Techniken unabdingbar für CMS, um die Effektivität des Triggersystems zu gewährleisten. Ich führe Studien zur Optimierung, Hardwareintegration und Nutzung eines Triggers, der auf einem Neuronalen Netz basiert durch. Ich zeige, dass Ereignisse des Prozesses HH -> bbWW, die ein einzelnes Muon enthalten, mithilfe eines kleinen neuronalen Netzwerkes effektiver selektiert werden können als mit klassischen Algorithmen. Ich demonstriere, dass dieses Netzwerk in die Hardware des L1T von CMS integriert werden kann
Impact of sphingosine-1-phosphate receptor 3 deficiency and serum sphingosine-1-phosphate level alteration in the development of intimal hyperplasia
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Overcoming Language Barriers in Mental Healthcare and Other Community Settings: Interpreting Practices and Training Measures
Get PDFLinguistic diversity within societies is a global reality, yet mental healthcare and other community services often fail to adequately reflect this, leading to language discordance between service users and providers. This dissertation explores interpreting practices to overcome language barriers and training measures for community interpreters and service providers. Five research objectives were developed and investigated in five individual studies.
In the first, a cross-sectional study was conducted among individuals identifying as interpreters and working in various community settings, such as (mental) healthcare, social care, education, or authorities in Germany. The findings provide an initial comprehensive and evidence-based overview of interpreters’ sociodemographic profiles, working conditions, (formal) training background, mental health status, and psychological distress regarding interpreting.
The second study was conducted to explore informal interpreting practices by investigating security guards serving informally as interpreters in a psychiatric hospital in South Africa. Interviews with mental healthcare professionals and security guards showed that this compromises communication quality and poses emotional risks for the security guards, yet it can be assumed that such practices persist due to a lack of effective alternatives.
In a third study, the impact of an interpreter’s presence on the communicative situation was investigated using the therapeutic alliance in a psychotherapeutic setting in Denmark as an example. Interpreters are an active part of the process, and their presence significantly changes the interaction. Conducting interpreter-mediated encounters effectively, including forming a good triadic therapeutic alliance, requires specialized training for both interpreters and service providers.
The fourth study focused on the development and evaluation of a generic training program for community interpreters in Germany. The mixed-methods study found improvements in interpreters’ knowledge, competence, self-efficacy, and increased self-perceived professionalism. The importance of formalized training and certification for enhancing service quality and interpreters’ professional status was highlighted.
In the fifth study, educational videos aiming at training service providers to work with interpreters across community settings were developed and evaluated. Interviews with service providers and experts in CI in Germany and Switzerland revealed that while the videos can increase providers’ knowledge and confidence, in-person practice is necessary for effective interpreter-mediated communication.
Overall, this dissertation provides valuable knowledge about the individuals working (informally) as interpreters, the impact of the interpreters’ presence on communication, and how to train service providers and interpreters to collaborate effectively. Beyond changes at an individual level, socio-political reforms at the institutional and systemic levels are required to ensure effective and professional interpreting practices and thus promote equitable service access to and provision of mental healthcare and other community services in linguistically diverse populations