Verwaltungsstrukturen und Herrschaftsinstitutionen in den britischen und französischen Kolonialimperien

Zusammenfassung Strukturell „begrenzte Staatlichkeit“ und nicht staatszentrierte Modi des Regierens sind keine Phänomene, die erst seit dem ausgehenden 20. Jahrhundert zu beobachten sind. Aus diesem Grund plädiert dieses Working Paper für die Übertragung des Governance-Begriffs auf vorund frühmoderne Gesellschaften. Anknüpfend an die neuere Diskussion um frühneuzeitliche Staatlichkeit steht hier nicht die mehr oder weniger monolithische Sicht auf einen sich mit Macht durchsetzenden monarchisch- absolutistischen Staat im Vordergrund, als vielmehr die Vielfalt staatlicher Dynamiken und der daran beteiligten Akteure. Das Working Paper fragt daher nach den historisch kontingenten Entwicklungspfaden zentralisierter Herrschaftsausübung. Hierdurch soll insbesondere die Heterogenität dieses Entwicklungsprozesses beleuchtet werden, der durch eine Ungleichzeitigkeit von nebeneinander bestehenden traditionellen und neueren Regierungs- und Verwaltungsstrukturen sowie durch immer wiederkehrende Prozesse der Aushandlung von Autorität gekennzeichnet ist

Collaboration in electronic resource provision in university libraries: SHEDL, a Scottish case study

This case study examines the growth of collaboration among Scottish higher education institutions. Following a summary of the work of the Scottish Confederation of University and Research Libraries (SCURL), more detailed information is provided on collaboration in the fields of acquisition, licensing, selection, and purchasing. Some of the UK background is outlined, relating to NESLi2 in particular, in order to illuminate the options within Scotland. The origins of negotiations on electronic resource provision within Scotland are described, drawing on developments in other countries including Ireland and Scandinavia. After initial setbacks, the implementation of the Scottish Higher Education Digital Library (SHEDL) from 2007 to 2009 is detailed. Current benefits arising from SHEDL are explained, and some possible future developments are discussed

Impeded Migration as Adaptation: COVID-19 and Its Implications for Translocal Strategies of Environmental Risk Management

In the debates over environmental impacts on migration, migration as adaptation has been acknowledged as a potential risk management strategy based on risk spreading and mutual insurance of people living spatially apart: migrants and family members that are left behind stay connected through a combination of financial and social remittances, joint decision-making and mutual commitment. Conceptualizing migration as adaptation through the lens of translocal livelihood systems enables us to identify the differentiated vulnerabilities of households and communities. COVID-19 and the restrictions on public life and mobility imposed by governments worldwide constituted a complex set of challenges for translocal systems and strategies, especially in the Global South. Focusing on examples, we highlight two points: first, the COVID-19 crisis shows the limits of migration and translocal livelihoods for coping with, and adapting to, climate and environmental risks. Second, as these restrictions hit on a systemic level and affect places of destination as well as origin, the crisis reveals specific vulnerabilities of the translocal livelihood systems themselves. Based on the translocal livelihoods approach, we formulate insights and recommendations for policies that move beyond the narrow, short-term focus on the support of migrant populations alone and address the longer-term root causes of the vulnerabilities in translocal livelihoods systems

Therapeutic drug monitoring of rivastigmine and donepezil under consideration of CYP2D6 genotype-dependent metabolism of donepezil

Background: The efficacy of acetylcholinesterase inhibitors (AChE-I) might depend on blood concentration. While rivastigmine metabolism is independent of the cytochrome P450 system, its isoenzymes, especially CYP2D6, metabolize donepezil. CYP2D6 polymorphisms can cause altered enzyme activity resulting in lower or higher than expected drug concentrations of donepezil. Objective: We investigated correlations between clinical efficacy and serum concentrations of rivastigmine and donepezil under special consideration of CYP2D6 genotype or gene dose-dependent metabolism of donepezil. Methods: Serum concentrations of donepezil and rivastigmine were measured by liquid chromatography - tandem mass spectrometry (LC-MS/MS). Real-time quantitative polymerase chain reaction (PCR) and allele-specific PCR were performed to assess CYP2D6 genotype and gene dose. Results: Patients treated with rivastigmine (n=28) or donepezil (n=48) were included in the study. Both gene dose and metabolism type significantly predicted the level of donepezil serum concentration (p=0.019 and p=0.013, respectively). In the rivastigmine group, changes of the word list delayed recall subtest before treatment and under stable medication were significantly associated with rivastigmine serum levels (beta=0.465;p=0.018). Drug serum concentrations were outside the recommended range in a substantial percentage of participants, which might have contributed to poor correlations between changes in cognitive measures and drug concentrations. Donepezil serum concentrations significantly depended on CYP2D6 gene dose. Conclusion: Testing AChE-I serum concentration should be considered in patients without clinical response to treatment or those with severe side effects. Patients with donepezil drug levels outside the recommended range might additionally profit from CYP2D6 genotyping or treatment with an AChE-I independent of CYP metabolism

Serum Concentrations of Cholinesterase Inhibitors in Patients With Alzheimer's Dementia Are Frequently Below the Recommended Levels

Background: Acetylcholinesterase inhibitors (AChE-I) are recommended for the treatment of cognitive symptoms but also of behavioral and psychological symptoms in dementia. They are widely used not only in Alzheimer's disease, but also in other forms of dementia. Efficacy of treatment might depend on serum concentration of the respective AChE-I. Objective: In patients with mild to moderate Alzheimer's dementia, we measured serum concentrations of hepatically metabolized donepezil and renally excreted rivastigmine and investigated possible modifiers. Additionally, we looked at correlations between serum concentrations and efficacy for both drugs. Methods: Serum concentrations of donepezil and rivastigmine were measured by liquid chromatography – tandem mass spectrometry (LC-MS/MS). Real-time quantitative polymerase chain reaction (PCR). Allele specific PCR were performed to determine CYP2D6 genotype and gene dose. Clinical efficacy was assessed by changes of the subtest wordlist delayed recall of the Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery (CERAD-NAB). Results: Sixty-seven patients treated with a stable dosage of donepezil 10 mg (n=41) or rivastigmine 9.5 mg (n=26) were included. Mean serum concentration of donepezil and rivastigmine were 41.2 and 6.5 ng/ml, respectively. Serum concentrations were below the recommended range in 73% of the subjects in the donepezil group and in 65% of the participants in the rivastigmine group. When applying a dose-related reference, ranges 63% of patients in the donepezil group and 32% in the rivastigmine group had concentrations below the expected range. Gene dose, sex, and duration of treatment significantly predicted donepezil serum concentration (p=0.046, p=0.001, p=0.030 respectively). Only for rivastigmine did the serum concentration significantly contribute to the regression model predicting changes on the subtest word list delayed recall (β=0.472; p=0.019). Conclusions: Serum concentrations of about two thirds of the patients were below the recommended range. When not looking at absolute values but at the dose-related reference ranges, these numbers improved but still 32%, respectively 63% of patients had low serum concentrations. High serum concentrations of rivastigmine predicted clinical response to cognition. Therapeutic drug monitoring might help to identify the cause of poor clinical response to cognition and behavioral and psychological symptoms in patients with AChE-I treatment

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Therapeutic Drug Monitoring of Rivastigmine and Donepezil Under Consideration of CYP2D6 Genotype-Dependent Metabolism of Donepezil

Background: The efficacy of acetylcholinesterase inhibitors (AChE-I) might depend on blood concentration. While rivastigmine metabolism is independent of the cytochrome P450 system, its isoenzymes, especially CYP2D6, metabolize donepezil. CYP2D6 polymorphisms can cause altered enzyme activity resulting in lower or higher than expected drug concentrations of donepezil. Objective: We investigated correlations between clinical efficacy and serum concentrations of rivastigmine and donepezil under special consideration of CYP2D6 genotype or gene dose-dependent metabolism of donepezil. Methods: Serum concentrations of donepezil and rivastigmine were measured by liquid chromatography - tandem mass spectrometry (LC-MS/MS). Real-time quantitative polymerase chain reaction (PCR) and allele-specific PCR were performed to assess CYP2D6 genotype and gene dose. Results: Patients treated with rivastigmine (n=28) or donepezil (n=48) were included in the study. Both gene dose and metabolism type significantly predicted the level of donepezil serum concentration (p=0.019 and p=0.013, respectively). In the rivastigmine group, changes of the word list delayed recall subtest before treatment and under stable medication were significantly associated with rivastigmine serum levels (beta=0.465;p=0.018). Drug serum concentrations were outside the recommended range in a substantial percentage of participants, which might have contributed to poor correlations between changes in cognitive measures and drug concentrations. Donepezil serum concentrations significantly depended on CYP2D6 gene dose. Conclusion: Testing AChE-I serum concentration should be considered in patients without clinical response to treatment or those with severe side effects. Patients with donepezil drug levels outside the recommended range might additionally profit from CYP2D6 genotyping or treatment with an AChE-I independent of CYP metabolism

Impeded Migration as Adaptation: COVID-19 and Its Implications for Translocal Strategies of Environmental Risk Management

In the debates over environmental impacts on migration, migration as adaptation has been acknowledged as a potential risk management strategy based on risk spreading and mutual insurance of people living spatially apart: migrants and family members that are left behind stay connected through a combination of financial and social remittances, joint decision-making and mutual commitment. Conceptualizing migration as adaptation through the lens of translocal livelihood systems enables us to identify the differentiated vulnerabilities of households and communities. COVID-19 and the restrictions on public life and mobility imposed by governments worldwide constituted a complex set of challenges for translocal systems and strategies, especially in the Global South. Focusing on examples, we highlight two points: first, the COVID-19 crisis shows the limits of migration and translocal livelihoods for coping with, and adapting to, climate and environmental risks. Second, as these restrictions hit on a systemic level and affect places of destination as well as origin, the crisis reveals specific vulnerabilities of the translocal livelihood systems themselves. Based on the translocal livelihoods approach, we formulate insights and recommendations for policies that move beyond the narrow, short-term focus on the support of migrant populations alone and address the longer-term root causes of the vulnerabilities in translocal livelihoods systems