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Cosmopolitan aging in urban Zanzibar: health, gender and transnational care spaces related to Oman
Get PDFPopulation aging, urbanization and transnationalization are three major developments shaping the 21st century all over the world and especially in Africa. This book takes up the case of the East African Swahili city of Zanzibar in Tanzania to illustrate the wide range of experiences of health, gender and care in heterogeneous urban contexts. Based on seventeen months of multi-sited ethnographic research in the city of Zanzibar (Tanzania) and Muscat (Oman), the author analyzes norms and practices of aging and caregiving from the perspectives of older Zanzibari, as well as their relatives and acquaintances within local, cosmopolitan and transnational spaces. This book makes a point for understanding elderhood not as a uniform and stable stage of life but that one should pay attention to diverse and ever changing health situations and their consequences for older persons’ experiences of aging and caregiving. An analysis from this perspective sheds light on gendered aspects of aging and care, and how older men and women’s access to social spaces opens-up and closes depending on their health situation. This study counters simplistic depictions of older men and women in Sub-Saharan Africa as solely tied to local places and spaces but it also argues against a newer trend of assuming aging and caring as completely transnational phenomena. Instead, by adding a new dimension - the concept of cosmopolitan aging - it provides insights into the many facets of everyday lives of older agents who interact actively with others to provide and receive care
The effects of low-load resistance training with blood flow restriction compared to high-load resistance training on maximum strength and muscle geometry in healthy middleaged individuals: a randomized controlled trial.
No full textThe effects of low-load resistance training with blood flow restriction compared to high-load resistance training on maximum strength and muscle geometry in healthy middle-aged individuals: a randomized controlled trial.
Background: Resistance training is integral to maintaining good health. Guidelines often recommend high-load resistance training (HL RT), which places substantial mechanical stress on muscles and tendons. However, for some individuals, less strenuous alternatives may be preferable. Blood flow restriction (BFR) training has emerged as a promising alternative that could offer similar benefits in terms of muscle growth and strength, though research is not yet exhaustive.
Methods: This thesis aimed to compare the effects of low-load BFR training (LL BFRT) and HL RT on maximum strength and muscle geometry. Nine participants were randomized into two groups: LL BFRT (n=3) and HL RT (n=6). The intervention lasted for 8 weeks. Muscle strength and geometry were assessed at baseline (PRE1 and PRE2) and mid-intervention (MID). Outcomes included maximum strength and muscle growth of knee extensors and flexors, assessed using an isokinetic dynamometer, maximal voluntary contraction (MVC), one-repetition maximum (1RM), and anatomical muscle cross-sectional area measured by ultrasound. Statistical analysis was performed using mixed linear models, adjusting for age and gender.
Results: Both groups exhibited significant increases in leg press isokinetic values, MVC, 1RM leg flexion, and 1RM leg extension. Analysis indicated significant effects of time and group, but no significant interaction effects between time and group.
Conclusions: LL BFRT provided muscle strength gains comparable to HL RT in this study. However, due to the small sample size, conclusions regarding muscle growth were inconclusive. Future research with larger sample sizes is needed to confirm these findings and explore additional effects, such as on muscle geometry
Telerehabilitation nach einem Schlaganfall: Eine Studie zur Benutzerfreundlichkeit und Funktionalität eines applikati-onsbasierten Trainingsprogramms
No full textHintergrund
Die Weiterentwicklung der Rehabilitationsmethoden für Schlaganfallpatient/innen ist von ent-scheidender Bedeutung, insbesondere beim Übergang von der stationären zur ambulanten Versorgung, wo die Motivation oft nachlässt und Unterstützung durch Therapeut/innen be-grenzt ist. Um dem entgegenzuwirken, werden digitale Anwendungen entwickelt, die Trai-ningsprogramme für zu Hause anbieten. Diese Studie evaluiert die Benutzerfreundlichkeit und Benutzererfahrung von „blended clinic“ bei Schlaganfallpatient/innen und Therapeut/innen.
Methoden
Die Single-Center-Studie an der Reha Rheinfelden verwendete die Methode des Rapid Itera-tive Testing. Primäre Endnutzer/innen hatten zwei Sitzungen und eine zwischengelagerte Testphase, um die Benutzerfreundlichkeit zu bewerten, während sekundäre Endnutzer/innen eine Sitzung hatten, um das System zu testen und zu bewerten. Die Benutzerfreundlichkeit wurde anhand der System Usability Scale, der Mobile Application Rating Scale, Feedback, Beobachtungen und Adhärenz bewertet.
Resultate
Acht Schlaganfallpatient/innen und zehn Therapeut/innen nahmen an der Studie teil. Die Mit-telwerte des SUS zeigten 87,2 ± 10,8 (Patient/innen) und 83,3 ± 11,3 (Therapeut/innen); MARS-G 3,9 ± 0,5 (Patient/innen) und 4,1 ± 0,4 (Therapeut/innen) in den Kategorien A-D, Benutzererfahrung 4,1 ± 0,5 (Patient/innen), Benutzerfreundlichkeit der Geräte 3,8 ± 0,8 (Pa-tient/innen) und Benutzererfahrung 4,2 ± 0,5 (Therapeut/innen). Eine/r von acht Patient/innen zeigte sich adhärent bei den Übungen und eine/r von acht war adhärent beim Tragen des Activity-Trackers.
Schlussfolgerungen
Die Anwendung „blended clinic“ wird von Schlaganfallpatient/innen und von Therapeut/innen als benutzerfreundlich und gut anwendbar eingeschätzt, jedoch gibt es Verbesserungspoten-tial. Ein angemessenes Training und Zeit für die Anpassung sind entscheidend für die richtige Nutzung. Darüber hinaus können zeitliche, motivierende Faktoren und die technische Funkti-onalität die Adhärenz der Patient/innen und den langfristigen Erfolg des Projekts verbessern
Langzeitbelastungsintoleranz bei Patienten mit Post-COVID-19 Syndrom: Eine spiroergometrische Analyse der kardiorespiratorischen Fitness mit Fokus auf pulmonal-vaskuläre und kardio-zirkulatorische Leistungsparameter
No full textHintergrund
Etwa 10-20% aller SARS-CoV-2-Infizierten leiden unter einem Post-COVID-19 Syndrom. Die SARS-CoV-2-Infektion zeigt sich meist als Multiorganerkrankung, die langfristige strukturelle Schäden an verschiedenen Organsystemen verursacht. Das Spektrum der Symptome und Folgeerscheinungen ist breit und variabel, wobei über die Mechanismen, die zu den Langzeitfolgen führen, noch immer wenig Konsens besteht. Die aktuelle Forschungslage zeigt sich jedoch einig, dass eine niedrigere Belastungstoleranz von Patienten mit Post-COVID-19 Syndrom vorliegt, insofern dass sich die kardiorespiratorische Fitness auch nach einem längeren Zeitraum nach der COVID-19 Infektion tiefer präsentiert.
Methoden
Die Spiroergometrie gilt als Goldstandard für die Feststellung der kardiorespiratorischen Fitness, Identifizierung von Organsystem-Limitationen und kann daher zur Erkennung von Belastungsintoleranzen eingesetzt werden. In dieser Masterarbeit werden Patienten mit Post-COVID-19 Syndrom mindestens 18 Monate nach Hospitalisierung mit gesunden Kontrollpersonen verglichen. Ziel ist es, mittels der Spiroergometrie Unterschiede in der kardiorespiratorischen Fitness anhand der VO2peak zu prüfen und zudem allfällige Differenzen bezüglich zwei ausgewählter pulmonal-vaskulärer (V̇ E/V̇ CO2 und PetCO2) und kardio-zirkulatorischer (O2-Puls und V̇ O2/work rate) Parameter zu untersuchen. Die Daten wurden im Rahmen der COR-PHYS Studie von Patienten mit Post-COVID-19 Syndrom (n=12) erhoben und mit Kontrollpersonen (n=12) aus der COmPLETE Studie mittels einer multiplen linearen Regression verglichen, wobei die Untersuchung mit einer Korrelationsanalyse ergänzt wurde.
Resultate
Die vorliegenden Daten haben gezeigt, dass die VO2peak bei den Patienten mit Post-COVID-19 Syndrom im Durchschnitt um 8,15 ml/kg/min (β = -1.06; p < 0.05) niedriger ist als bei den gesunden Kontrollpersonen. Ausserdem konnte bezüglich der OUES (p < 0.05) ein signifikanter Unterschied zwischen den Gruppen festgestellt werden. Die pulmonal-vaskulären Parameter (V̇ E/V̇ CO2 und PetCO2 an der VT1) unterscheidet sich nur geringfügig zwischen den Patienten mit Post-COVID-19 Syndrom und gesunden Kontrollpersonen. Sowohl der O₂-Puls (β = -0.34) wie auch die V̇ O2/work rate (β = -0.55) weisen eine Differenz auf. Zwischen der VO2peak und O2-Puls konnte eine starke Korrelation (Pearson's r = 0,63, p < 0.001) beobachtet werden.
Schlussfolgerungen
Die vorliegende Masterarbeit zeigt, dass eine verminderte kardiorespiratorische Fitness (anhand der VO2peak) bei Patienten mit Post-COVID-19 Syndroms im Vergleich zu gesunden Kontrollpersonen auch nach über 18 Monaten Bestand hat. Der O₂-Puls wie auch die V̇ O2/work rate sind bei den Patienten mit Post-COVID-19 Syndrom tiefer als bei den gesunden Kontrollen. So lassen sich Limitationen und Zusammenhänge vor allem bei den kardio-zirkulatorischen Parameter abbilden, obschon der Sauerstoffpuls als einziger Parameter eine starke Korrelation zur VO2peak aufweist
Sleep in children and adolescents with major depressive disorder: associations with low-grade inflammation and omega-3 polyunsaturated fatty acids
No full textThe present cumulative dissertation aimed to investigate the association between sleep and low-grade inflammation in children and adolescents diagnosed with major depressive disorder (MDD) and to explore potential associations between Omega-3 polyunsaturated fatty acids (n-3 PUFAs) and sleep in pediatric MDD. The aim of the first manuscript was to investigate the associations between sleep disturbances and plasma levels of high-sensitivity C-reactive protein (hsCRP), an indicator of low-grade inflammation, in a sample of 256 children and adolescents with MDD of moderate to severe symptom severity. The results indicated a significant association between clinician-rated hypersomnia and middle insomnia symptoms with hsCRP in pediatric depression, not linked to alterations in body mass index. The second manuscript aimed to examine the link between both objectively measured and self-reported sleep parameters and low-grade inflammation, indicated by hsCRP, in a younger population. Comprehensive sleep assessments were conducted, including a single-night sleep electroencephalogram (EEG) recording, self-reported sleep data, and actigraphy measurements. To further clarify the potential influence of depression on the relationship between sleep and inflammation, two distinct groups were included: one group of children and adolescents diagnosed with MDD exhibiting moderate to severe symptoms of depression (n = 29), and a control group of healthy peers (n = 29). In the MDD group, the results indicated an inverse association between hsCRP levels and time spent in slow-wave sleep (SWS), suggesting that alterations in the architecture of SWS might play a significant role in modulating low-grade inflammatory processes in pediatric MDD. In the third manuscript, potential associations between n-3 PUFAs and sleep in pediatric depression were investigated. Self-reported and objectively assessed sleep data, along with red blood cell levels of n-3 PUFAs, were collected from 29 children and adolescents with MDD and 30 healthy controls. The findings indicated a significant association between higher levels of n-3 PUFAs, particularly docosahexaenoic acid (DHA), and increased total sleep time in children and adolescents diagnosed with MDD. Differences between eicosapentaenoic acid (EPA) and DHA in their associations with sleep outcomes suggest a more significant role for DHA in modulating sleep-related processes in pediatric MDD
Interventions and strategies for urogenital schistosomiasis elimination in Zanzibar
Get PDFUrogenital schistosomiasis is caused by Schistosoma haematobium and can lead to severe morbidity if untreated. The human-snail-human life cycle of S. haematobium can be interrupted with treatment, snail control and behavior change interventions. The Zanzibar islands, United Republic of Tanzania, have achieved low overall prevalence nowadays; thus, their historical interventions can guide other sub-Saharan African countries towards the same goal. At the same time, questions arise about whether large-scale treatment is still justified in areas with a very low prevalence. Novel strategies are now needed to map environmental factors and human infection, identify clusters, and address spatial heterogeneity of infection focally.
The current thesis addresses these questions in several ways. A systematic review of 100 years of schistosomiasis and snail-related research on Zanzibar was performed to identify interventions and their impact on the S. haematobium prevalence. The impact of seven years of mass drug administration (MDA) and of a 16-month treatment gap on S. haematobium prevalence was determined. Finally, as part of the SchistoBreak study (2020-2024) being implemented to develop novel strategies for the elimination of schistosomiasis, two cross-sectional surveys in schools and households utilized micro-mapping to assess the impact of test-treat-track-test-treat (5T) interventions as an alternative to MDA in low-prevalence areas.
A hundred years of interventions resulted in a low overall prevalence of <5% in 2020. After a 16-month gap of MDA, spatial heterogeneity of S. haematobium infection on the islands was observed and became more pronounced when the prevalence rebounded primarily in hotspot areas. A novel strategy for infection mapping within the SchistoBreak study demonstrated the feasibility of finding pre-randomized households in remote settings. After one year of 5T interventions in low-prevalence areas, no significant prevalence increase was revealed.
A combination of MDA, including treating adults and preschool-aged children, snail control, and behavior change measures are crucial to reducing the S. haematobium prevalence in hotspot areas. Environmentally friendly snail control and new intervention grounds for behavior change measures need to be explored. To compare the schistosomiasis prevalence across countries and to create a global prevalence map, micro-mapping guidelines by the World Health Organization are required. In low-prevalence settings, targeted interventions present alternatives to MDA; however, future studies need to assess the optimal interventions required to maintain or further reduce the prevalence towards interruption of transmission
Electricity markets and policy uncertainty: external pressure points for nuclear decommissioning
Get PDFThis thesis provides an integrated assessment on the influence of electricity markets and policy uncertainty on nuclear plant financing, early nuclear power plant (NPP) shutdown dynamics, and nuclear waste management. The first paper investigates whether out-of-market support schemes were justified for state subsidised NPPs in the New York Independent System Operator (NYISO) and PJM wholesale electricity markets over a five-year period between 2017 and 2021. The results indicated that for long stretches of time, the sample NPPs were in a solid financial position, relying solely on market revenues without the need for state support schemes (i.e., zero-emission credit schemes). The findings further suggest that under a dual state and federal support scheme system, the magnitude of excess profits would be substantial. The second paper takes a forward-looking approach and evaluates the electricity market impacts of a premature nuclear plant shutdown and the spillover effects on the long-term income conditions of NPPs. The paper developed a bespoke bottoms-up dispatch model for the NYISO and four regional electricity markets. Results indicate that shutting down upstate New York NPPs in 2018 and 2021 induced a slightly higher cost burden for New York consumers compared to the total zero-emission credit (ZEC) expenditures. In contrast, phasing out upstate NPPs in 2030 induced a lower cost burden compared to the total ZEC expenditure, mainly due to a high credit price. In the long-term, integrating a carbon price mechanism into the NYISO market would raise average NYISO prices, thereby enhancing the long-term income conditions of NPPs, and ensuring sufficient accumulation of nuclear decommissioning funds. The third paper explores the dynamic interaction between government policy decisions and firm investment decisions into a consolidated interim storage facility (CISF) using a simplified game theoretic framework. Results indicate that firms should always commit to constructing a CISF regardless of the government's final policy decision. The final government decision under various sensitivity iterations is an equal split between long-term contract and allowing firms to privately operate the CISF
From mutations to meanings: using deep mutational scanning to understand sequence-function relationships through protein-protein interaction specificity
No full textOne of the fundamental questions of biological and genetic research asks how genotypes are translated into phenotypes or, more specifically, how sequence is translated into molecular function. Protein-protein interactions (PPIs) form the functional backbone of a cell by forming large protein interaction networks (PINs) that coordinate molecular processes. To establish these networks within the crowded cellular environment and prevent unwanted crosstalk, most PPIs are highly specific. PPI specificity is encoded in sequence, and mutations can alter specificity, rewire PINs, and cause diseases. Therefore, understanding how sequence determines interaction specificity is essential for understanding how molecular processes are regulated and the mechanisms of diseases. However, finding determinants of specificity for PPIs of interest, let alone predicting them computationally remains a long-standing challenge.
Ground-breaking advances like AlphaFold2 have brought forward the challenge of predicting PPIs, yet they still cannot pin down specific determinants of specificity or account for quantitative changes or loss of interactions in case of mutations. In order to overcome these limitations, other datasets to train computational models are required.
These datasets must contain quantitative measurements of how perturbations (mutations) alter PPIs to understand how individual positions within the protein contribute to its specificity. A family of assays that is well-suited to generate such datasets at large scale is deep mutational scanning (DMS). Here, hundreds of thousands of sequence alterations of a protein function of interest can be measured in parallel.
In this work, a combined assay of DMS and a split-DHFR enzyme-protein complementation assay (ddPCA) was applied. ddPCA allows parallel assessment of the effect of thousands of mutations on PPIs. The family of human basic leucine zipper (bZIP) interaction domains was used as a model system. They display highly diverse specificities while being conserved in sequence and thus represent an appropriate model for the assessment of determinants of specificity at the network level.
To establish the assay, a first screen was performed in which was measured how every single point mutation in the JUN zipper altered JUN’s interaction with all 54 wildtype bZIPs. With the aid of
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thermodynamic modeling, this provided the first comprehensive map of global effects on all of a protein’s binding partners and further revealed determinants of specificity for individual interactions within the network.
The assay was then optimized in order to identify potential sources of non-linearities that might result in biases when further scaling up the screen.
Finally, ddPCA was used to perform the most extensive DMS to date in which all single point mutants of the entire bZIP family were assayed for their interaction specificities and abundance. The dataset of more than two million pairwise interactions revealed network-wide mutation effects that can inform our understanding of bZIP network properties and the mechanisms of disease. Finally, this data was used to develop a deep learning model that can predict bZIP interactions from sequence and holds promise to pioneer a new generation of models that go beyond the limits of models such as AlphaFold2 and are able to capture quantitative aspects of the sequence-function relationship.
In this thesis, an experimental and analytical framework to solve sequence-function relationships was developed. It allows revealing the genetic architecture of PPI specificity in the bZIP family and build a domain-specific sequence-function model. Further, when applied more generally to different domain families with different architectures, it can aid with generalizing the model to all PPIs
Establishing the basis for rabies control and elimination in Liberia
Get PDFBackground: Rabies is a fatal zoonotic disease. Every year, an estimated 59'000 rabies-related deaths are reported globally, affecting four out of ten children. In endemic regions, domestic dogs are the main reservoir of rabies, transmitting the disease to humans through the bite or scratch of an infected animal. Although rabies in animals and humans is notifiable in Liberia, surveillance is primarily passive. There are no accurate estimates of the "true" rabies situation in the country. Based on these shortcomings and the global drive to end dog-related human rabies deaths by 2030, this Ph.D. work aimed to establish animal rabies diagnostics and gather relevant baseline information that is crucial for control programs for rabies elimination in Liberia.
Objectives: This PhD thesis achieved the following objectives, i) established animal rabies diagnostics at the Central Veterinary Laboratory, ii) surveyed the community's knowledge about rabies and vaccination scenarios, and iii) investigated molecular and phylogenetic characteristics of circulating rabies strains in Liberia.
Methods: We used a One Health approach, collaborating between key national and international rabies stakeholders, to successfully establish three animal rabies diagnostic tests. We used an opportunistic sampling approach to collect and diagnose the first animal rabies strain in post-war Liberia. A randomized cross-sectional knowledge, attitude, and practice (KAP) household survey related to dog rabies and was used to estimate the dog population survey in rural and urban households. Based on this data, we developed three scenarios for mass dog vaccination. In addition, we strengthened the rabies surveillance system to collect suspected animal rabies samples to perform a genome-based phylogenetic analysis of RABV isolates circulating in Liberia.
Results: Analyses of the first rabies samples revealed that all isolates belonged to the Africa 2 lineage; Subgroup H circulates in the domestic dog population. This finding subsequently flagged Liberia as an endemic rabies country. It contributed, among other factors, to the country’s score of 1.5/5 on the Stepwise Approach towards Rabies Elimination (SARE) tool, indicating that Liberia is in the early stages of dog rabies control. Results from the cross-sectional survey conducted in rural and urban households estimated a mass vaccination cost of USD 1.5 – 1.6 million to vaccinate the total dog population for one vaccination round. Rabies knowledge among participants was low, thus influencing risky practices. Results from strengthening rabies surveillance identified the disease hotspots. It further demonstrated that RABV isolates circulating in Liberia were clustered into the phylogroup H within the Africa 2 clade. This information is necessary for future rabies control and eradication programs.
Conclusion: This PhD work generated relevant information for rabies control in Liberia. Baseline information is crucial for effective rabies control. Our findings obtained from the household survey are important for developing a national rabies control strategy and intervention. At the same time, findings from the molecular and phylogenetic study are vital to developing appropriate vaccination strategies for dogs and allow their effectiveness to be assessed in Liberia
Bone Morphogenetic Proteins as regulators of cortical excitation and inhibition
Get PDFPlasticity is the underlying mechanism for neuronal circuits to develop and adapt to the environment for organisms to regulate different body states, learn new tasks, form memories and use their cognitive abilities. Over the last century, studies demonstrated that neurons utilize the plethora and variety of their synaptic properties to store and integrate the environmental cues on shorter timescales from milliseconds to hours. However, how neurons, in particular synapses, adapt to longer periods of stimuli which is essential for learning a new task and memory consolidation, remains largely unknown.
Secreted molecules, especially growth factors, are great candidates for such adaptations in the brain areas such as cortex where multiple types of cells constantly work in harmony and exchange information to adapt to sensory stimuli. In this thesis, I investigated whether Bone Morphogenetic Proteins (BMPs), key players of the patterning during embryonic development, are re-utilized as a transcellular signal underlying homeostatic plasticity in the adult somatosensory cortex.
BMPs are ligands of the transforming growth factor family (TGF) which are encoded by more than 20 genes in vertebrates. I first contributed to a collaborative study with the group of Ralf Schneggenburger in EPFL, Lausanne. In this project, we explored if BMP signaling regulates the development of inhibitory long-term potentiation (iLTP) from Parvalbumin interneurons (PV interneurons) onto layer 4 principal cells in the primary auditory cortex (A1) during critical period plasticity. Conditional/genetic deletion of BMP receptor-1a (Bmpr1a) and 1b (Bmpr1b) demonstrated that loss of BMP signaling in PV interneurons results in disruption of iLTP formation onto layer 4 principal neurons.
In my main project, I screened BMP ligands to identify their sites of expression in the mouse neocortex and examined whether neuronal network activity can mobilize the signaling. For the first time, I demonstrated that the BMP pathway is active in mature neurons of the mouse brain and can be recruited by neuronal activity. By advancing a reporter generated from BMP responsive element of the target genes, I showed that BMP2 mobilization from principal cells are responded by Parvalbumin interneurons through SMAD1, a critical transcriptional mediator of the BMP pathway. This was quite striking as this is the first evidence that BMP signaling can be transcellularly signaled between the key players of excitation-inhibition balance in the sensory cortices. Next, I coupled Chromatin immunoprecipitation (ChiP) with RNA sequencing and identified target genes of BMP2 ligand in cortical neurons. Surprisingly, we found that the SMAD1 transcription factor regulates expression of select activity-induced immediate early genes (IEGs), genes encoding for extracellular matrix components, and glutamatergic synaptic proteins. Therefore, I focused my further experiments on the investigation of synaptic drive onto Parvalbumin interneurons to ask if loss of SMAD1 from Parvalbumin interneurons cause alterations in their synaptic connectivity and cellular properties. By coupling electrophysiological, anatomical and behavioral analyses, I demonstrated that BMP2-SMAD1 signaling is essential to maintain excitation-inhibition in balance in the adult somatosensory cortex.
In summary, this work reveals that developmental signaling molecules are re-used for trans-cellular signaling in neurons to establish synaptic connectivity during the critical periods and maintain excitation-inhibition in balance in the adult cortex