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Natural Resource Rents, Autocracy and Economic Freedom
No full textThis paper theoretically and empirically investigates the effect of natural resource rents on the process of economic liberalization and a potential moderating effect of the level of democracy. A simple political-economic model is developed in which the government in an autocratic country faces a trade-off between liberalizing the economy to broaden the tax base on the one hand and consolidating its political power by preventing the rise of an economically independent middle class striving for political participation on the other hand. Whilst the theoretical model predicts that rents from natural resources lead to economic liberalization in both autocratic and democratic countries, the empirical analysis finds evidence that increasing resource abundance may lead to deliberalization in autocracies but may promote liberalization in democracies. The empirical evidence is robust to using both static panel data methods that control for unobserved country heterogeneity as well as a dynamic GMM estimator that further controls for potential endogeneity issues
The Die is Cast – Factors Influencing Mortality during the COVID-19 Pandemic
No full textSince the beginning of the year, almost the entire world has been thrown off course by the outbreak of the COVID-19 pandemic, which has caused health, social and economic challenges. In an international comparison it can be seen that the mortality rates vary widely between countries. This study therefore aims to investigate the quality of international healthcare systems and their potential risk factors in order to explore the differences in mortality. After the derivation of suitable variables and the collection of a widespread data set, we were able to detect with six different OLS regressions that the mortality rate significantly decreases with a higher number of hospital beds and increases with a higher proportion of elderly population (p < 0.05 respectively). This work also succeeded in partly explaining the varying international COVID-19 mortality rates with an already existing health economic index (adj. R2 = 28.4%) and an own set of variables (adj. R2 = 27.7%). The association of the quality of healthcare systems as well as risk factors with COVID-19 mortality rates might provide important implications
for future policy decisions
Effects of Tetrahydrolipstatin on Glioblastoma in Mice: MRI-Based Morphologic and Texture Analysis Correlated with Histopathology and Immunochemistry Findings : A Pilot Study
No full textGlioblastomas are themost aggressive brain tumors, and affected patients still only
have an extremely poor prognosis with today’s therapeutic options. Further developments are still
necessary, particularly in therapeutic approaches. Orlistat can act as an antitumor agent as it inhibits
fatty acid synthase, decreases tumor cell proliferation, and stimulates tumor cell apoptosis. Investigations
conducted on breast, pancreatic, hepatic, and colorectal tumors showed that FASN—fatty acid
synthase, a protein that catalyzes the de novo synthesis of long-chain fatty acids—is strongly upregulated.
Using an animal model, we tested whether the drug’s effects could be demonstrated visually,
quantitatively, and by texture analysis based on MR studies. Histology and immunochemistry were
used as references. The key results of the present study are as follows: Firstly, a significant difference
was found between orlistat-treated and untreated tumors in MRI studies based on morphology and
texture analyses. Secondly, the expression of FASN was reduced in the orlistat group, which, however,
did not result in a higher apoptosis rate in the treatment group. Our findings suggest that some
effects of orlistat on tumor cell proliferation must have taken place during therapy. Further studies
should investigate the effects of FASN inhibition when combined with targeted therapies.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Higher sediment redistribution rates related to burrowing animals than previously assumed as revealed by time-of-flight-based monitoring
No full textBurrowing animals influence surface microtopography and hillslope sediment redistribution, but changes often remain undetected due to a lack of automated high-resolution field monitoring techniques. In this study, we present a new approach to quantify microtopographic variations and surface changes caused by burrowing animals and rainfall-driven erosional processes applied to remote field plots in arid and Mediterranean climate regions in Chile. We compared the mass balance of redistributed sediment between burrow and burrow-embedded area, quantified the cumulative sediment redistribution caused by animals and rainfall, and upscaled the results to a hillslope scale. The newly developed instrument, a time-of-flight camera, showed a very good detection accuracy. The animal-caused cumulative sediment excavation was 14.6 cm3 cm−2 yr−1 in the Mediterranean climate zone and 16.4 cm3 cm−2 yr−1 in the arid climate zone. The rainfall-related cumulative sediment erosion within burrows was higher (10.4 cm3 cm−2 yr−1) in the Mediterranean climate zone than the arid climate zone (1.4 cm3 cm−2 yr−1). Daily sediment redistribution during rainfall within burrow areas was up to 350 %(40 %) higher in the Mediterranean (arid) zone compared to burrow-embedded areas and much higher than previously reported in studies that were not based on continuous microtopographic monitoring. A total of 38 % of the sediment eroding from burrows accumulated within the burrow entrance, while 62 % was incorporated into hillslope sediment flux, which exceeds previous estimations 2-fold. On average, animals burrowed between 1.2–2.3 times a month, and the burrowing intensity increased after rainfall. This revealed a newly detected feedback mechanism between rainfall, erosion, and animal burrowing activity, likely leading to an underestimation of animal-triggered hillslope sediment flux in wetter climates. Our findings hence show that the rate of sediment redistribution due to animal burrowing is dependent on climate and that animal burrowing plays a larger than previously expected role in hillslope sediment redistribution. Subsequently, animal burrowing activity should be incorporated into soil erosion and landscape evolution models that rely on soil processes but do not yet include animal-induced surface processes on microtopographical scales in their algorithms.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Orientia tsutsugamushi: A life between escapes
No full textTo replicate within host cells, intracellular bacteria have evolveddifferent strategies to invade, replicate, persist in, and eventually exitfrom their hosts. The intracellular lifestyle requires consecutive exitevents, in which microorganisms must overcome host cell mem-branes, and enter and adapt to new compartments. These exit eventsare critical steps in the microbial life cycle and are usually required forbacterial replication and spread.Current concepts on the exit events of intracellular bacteriahave been derived from the thorough study of model organisms,such asSalmonella,Shigella, Listeria,orMycobacteriumspecies. Incontrast, the exit strategies of many nonmodel—yet oftenmedically relevant—bacterial species are so far only known inbroad outline.The causative agent of scrub typhus,Orientia tsutsugamushi(Ot), which belongs to the order of Rickettsiales, is an importantbut neglected human pathogen whose exit mechanisms havebeen poorly characterized. This is due to the lack of tools forthe genetic manipulation ofOtand to the experimentalchallenges of working with a biosafety level 3 pathogen (Salje,2017). A refined knowledge of this pathogen's exitstrategies could define new targets for therapeutic approaches,for example, against long‐term persistence. This brief articlesummarizes the current state of knowledge, highlights common-alities and relevant differences to other intracellular bacteria, anddefines questions and possible novel approaches to decipher theexit mechanisms of Ot.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Non-cooperative and Cooperative Policy Reforms under Uncertainty and Spillovers
No full textWhen countries need to implement costly economic policy reforms,
these often imply uncertainties about their effectiveness for the home
country and their spillovers to other countries. We develop a model to
show that under these circumstances countries implement too few or
too many policy reforms. From a social perspective, too many reforms
follow if the spillover effects of reforms become sufficiently uncertain.
Since centralization of policies to correct ineffcient policies is often
not possible, we look for alternative instruments that can restore the
effcient level of reforms. We compare subsidizing reform efforts with
insuring against bad outcomes, and argue that subsidies are advanta-
geous in terms of requiring less information for implementation
Target templates and the time course of distractor location learning
No full textWhen searching for a shape target, colour distractors typically capture our attention. Capture is smaller when observers search for a fixed target that allows for a feature-specific target template compared to a varying shape singleton target. Capture is also reduced when observers learn to predict the likely distractor location. We investigated how the precision of the target template modulates distractor location learning in an additional singleton search task. As observers are less prone to capture with a feature-specific target, we assumed that distractor location learning is less beneficial and therefore less pronounced than with a mixed-feature target. Hierarchical Bayesian parameter estimation was used to fit fine-grained distractor location learning curves. A model-based analysis of the time course of distractor location learning revealed an effect on the asymptotic performance level: when searching for a fixed-feature target, the asymptotic distractor cost indicated smaller distractor interference than with a mixed-feature target. Although interference was reduced for distractors at the high-probability location in both tasks, asymptotic distractor suppression was less pronounced with fixed-feature compared to mixed-feature targets. We conclude that with a more precise target template less distractor location learning is required, likely because the distractor dimension is down-weighted and its salience signal reduced.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Application of UV-radiation and UV-responsive nanocapsules for skin antisepsis
No full textAngesichts der weltweiten Belastung des Gesundheitswesens durch postoperative Wundinfektionen (SSI) und der steigenden Prävalenz multiresistenter Bakterien, war das Ziel dieser Dissertation die Umsetzung zweier neuartiger und innovativer Ansätze für eine verbesserte Hautantisepsis. Haarfollikel stellen ein dicht kolonisiertes Erregerreservoir dar. Bei langwierigen chirurgischen Eingriffen kann es daher zu einer Rekolonisierung der Hautoberfläche aus diesem Reservoir, und der Verschleppung potenzieller Krankheitserreger in das Operationsgebiet, kommen. Es ist bekannt, dass SSI in 90% aller Fälle durch endogene Keime verursacht werden. Daraus ergeben sich zwei mögliche Ansätze für eine verbesserte Hautantisepsis: die Dekontamination tiefer Bereiche der Haarfollikel und die wiederholte intraoperative Dekontamination der Haut. Der erste Teil dieser Dissertation zielte auf die Anwendung eines pharmazeutisch basierten Ansatzes zur verbesserten Hautantisepsis ab. Basierend auf dem so genannten Ratscheneffekt dringen Nanopartikel in Haarfollikel ein, wenn äußere Kräfte auf sie einwirken. So ist bekannt, dass mit Nano-Delivery-Systemen eine deutlich tiefere follikuläre Penetration von Therapeutika erreicht werden kann als mit der Anwendung von freien Wirkstofflösungen. Eine gezielte Eradikation könnte also durch eine kontrollierte Freisetzung von Antiseptika in den tieferen Segmenten der Haarfollikel erfolgen, während diese Segmente für nicht partikuläre Substanzen unzugänglich sind. Für eine gezielte und schnelle Freisetzung des in den Nanokapseln (NCs) enthaltenen Antiseptikums wurde Ultraviolett A (UVA) Licht verwendet, da es die dermalen Hautbereiche erreichen kann. Dieser Ansatz wurde mit UVA Licht emittierenden Dioden (LED) sowie biokompatiblen photoresponsiven NCs verfolgt. Die erste von zwei Studien konzentrierte sich auf Prinzipexperimente zum Nachweis der Möglichkeit einer follikulären Penetration und intrafollikulären UV-getriggerten Wirkstofffreisetzung unter Verwendung von biokompatiblen Polyurethan (PU)-NCs. Anhand eines ex vivo Schweinehautmodells wurde ein UVA-abhängiger Abbau der NCs bei einer mittleren follikulären Eindringtiefe von etwa 500 µm festgestellt, wobei der Modellwirkstoff Sulforhodamin 101 (SR101) in kryohistologischen Schnitten mit konfokaler Laser-Scanning-Mikroskopie (CLSM) verfolgt wurde. In einem weiteren Ansatz wurden Hydroxyethylstärke (HES)-NCs verwendet, die auf der gleichen Technologie basierten. Mit diesen konnte eine vergleichbare follikuläre Eindringtiefe erreicht werden. In einem abschließenden Experiment, bei dem HES-NCs mit eingekapseltem Ethanol verwendet wurden, konnte hinsichtlich der Dekolonisierung kein signifikanter Unterschied zu einer partikelfreien Kontrolle (80% Ethanol) auf der ex vivo Schweineohrhaut festgestellt werden, was zeigt, dass die Wahl der Nanoträgermaterialien immer mit dem Anwendungsbereich und der Kompatibilität mit der kontinuierlichen Phase abgestimmt werden sollte.
Ergänzend dazu stellt Fern-UVC-Licht (UVC unter einer Wellenlänge von 240 nm) den zweiten Ansatz zur Dekontamination der Hautoberfläche dar, da es sich sehr leicht sequentiell anwenden lässt und somit rekolonisierte Flächen schnell desinfizieren kann um SSI zu verhindern. Fern-UVC-Strahlung hat aufgrund ihrer hohen Energie den Vorteil, dass sie resistenzfrei Pathogene durch die sofortige Erzeugung von DNA-Läsionen inaktiviert. Im Gegensatz zur UVC-Strahlung von 254 nm, die meist zur Desinfektion von Wasser und Oberflächen eingesetzt wird, wird sie in der obersten, nicht nukleierten Schicht der Haut, dem Stratum corneum, stark absorbiert. Daher ist die Penetration von Fern-UVC-Photonen in die Lebendepidermis nur begrenzt möglich. Im Rahmen dieser Arbeit wurde eine neuartige LED, die Fern-UVC-Licht mit einer Peak-Wellenlänge von 233 nm emittiert, an verschiedenen Hautmodellen hinsichtlich der Bildung von DNA-Schäden und freien Radikalen umfassend auf ihre Hautverträglichkeit geprüft. Dabei wurden zuvor von den Projektpartnern der Universitätsmedizin Greifswald ermittelte mikrobiozide Dosen eingesetzt. Bei einer Anwendungsdosis von 40 bis 60 mJ/cm2 konnte eine vollständige Eradikation von Methicillin-resistenten Staphylococcus aureus (MRSA) auf Agarplatten und Keimträgern beobachtet werden. Die Bestrahlung mit mikrobiozidem 233 nm Fern-UVC führte zu geringeren DNA-Schäden in intakter ex vivo Humanhaut im Vergleich zu 10% einer minimalen Erythemdosis (MED) UVB-Strahlung. Darüber hinaus war die Bildung freier Radikale in rekonstruierten humanen Epidermismodellen geringer als bei sichtbarer und nahinfraroter (VIS–NIR) Bestrahlung, die einem 20-minütigen Aufenthalt in der Mittagssonne entspricht. Um der Frage nachzugehen, ob 233 nm Fern-UVC-Strahlung auch während chirurgischer Eingriffe an Wunden angewandt werden kann, wurde in der Folgestudie ein ex vivo Wundmodell zur Risikobeurteilung von 233 nm Fern-UVC-Strahlung untersucht. Hier wurde nach Bestrahlung mit 233 nm Fern-UVC eine Zunahme und Verlagerung von DNA-Läsionen in tiefere Bereiche der wunden Haut beobachtet. Interessanterweise führte das Auftragen von künstlichem Wundexsudat auf die exponierte Lebendepidermis vor der Bestrahlung zur Nachahmung der photoprotektiven Funktion eines intakten Stratum corneum. Darüber hinaus wurde festgestellt, dass in der Wunde eine gewisse Menge an freien Radikalen gebildet wird, was die Wundheilung unterstützen könnte. Um den Einfluss der Melaninkonzentration zu ermitteln, wurde menschliche Haut verschiedener Hauttypen ex vivo mit 222 nm und 233 far-UVC-Licht sowie mit breitbandigem UVB-Licht bestrahlt. In dieser Studie zeigte sich, dass die Bildung von DNA-Läsionen bei dunklen Hauttypen nach Bestrahlung mit 233 nm geringer war als bei hellen Hauttypen. Die Bestrahlung bei 222 nm verursachte jedoch aufgrund ihrer begrenzten Eindringtiefe keine hauttypabhängigen Unterschiede. Im Gegensatz dazu verursachte UVB eine starke Divergenz zwischen hellen und dunklen Hauttypen bei der Anwendung von 10% einer MED. Die Melaninkonzentration unterscheidet sich zwischen hellen und dunklen Hauttypen in der oberen Epidermis weniger als in den tiefen Schichten der Epidermis. Dies führt, basierend auf der maximalen Eindringtiefe der jeweiligen Wellenlänge, zu hauttypabhängigen Abweichungen in der Verträglichkeit der Strahlung.
Zusammenfassend lässt sich sagen, dass der in dieser Dissertation untersuchte nanopartikelbasierte Ansatz zur Hautdekolonisierung durch den Fern-UVC-Licht-basierten Ansatz sinnvoll ergänzt wird und beide Ansätze Potenzial für eine präoperative sowie intraoperative Hautantiseptik besitzen. Dennoch müssen für eine endgültige Umsetzung noch deutliche Optimierungen auf pharmazeutischer Seite gesucht werden. Der Einsatz von Fern-UVC-LEDs zur Dekontaminierung der Hautoberfläche wurde in der vorliegenden Arbeit erstmals umfassend behandelt. Auch hier müssen für die endgültige Umsetzung weitere Studien zur Risikobewertung durchgeführt werden.Based on the global health care burden caused by surgical site infections (SSI) as well as the rising prevalence of multi-drug resistant bacteria this dissertation suggests the implementation of two novel and innovative approaches for an advanced skin antisepsis. Hair follicles are known to represent a densely colonized reservoir of pathogens. During prolonged surgical procedures, recolonization of the skin surface can therefore occur from this reservoir transmitting pathogens into the surgical field. It is known that SSI are caused by endogenous germs in 90% of all cases. This leads to two possible approaches for improved skin antisepsis: targeted decontamination of deep sections of hair follicles and repetitive intraoperative decontamination of the skin. The first part of this dissertation addresses the application of a pharmaceutical-based approach for enhanced skin antisepsis. Based on the so-called ratchet effect, nanoparticles penetrate into hair follicles when external forces are applied. Thus, it is known that a significantly deeper follicular penetration of therapeutics can be achieved using nano-delivery systems as compared to the application of free active ingredient solutions. A targeted eradication could therefore be induced by a controlled release of antiseptics in the deeper segments of the hair follicles, whereas these segments are inaccessible to non-particulate substances. For a targeted and rapid release of the antiseptic contained in nanocapsules (NCs), ultraviolet A light (UVA) was utilized due to its accessibility to the dermal portions of the skin. This approach was pursued using UVA light emitting diode (LED) systems as well as biocompatible photo-responsive NCs. The first of two studies focused on principal experiments to evidence the possibility of follicular penetration and intrafollicular UV-triggered drug release using biocompatible polyurethane (PU)-NCs. Using an ex vivo porcine skin model, UVA-responsive degradation of the NCs at a mean follicular penetration depth of approximately 500 µm was obtained tracking the model drug sulforhodamine 101 (SR101) in cryohistological slices with confocal laser scanning microscopy (CLSM). In a follow-up approach hydroxyethyl starch (HES)-NCs based on the same technology were utilized. With these, a comparable follicular penetration depth could be achieved. In a final microbiological experiment utilizing HES-NCs with encapsulated ethanol, no significant difference to a particle-free control (80% ethanol) could be observed on ex vivo porcine ear skin showing that the choice of nanocarrier materials should always be based on the field of application and compatibility with the continuous phase.
Complementary to this, far-UVC light (UVC < 240 nm) represents the second approach for improved skin surface decontamination as it is very easy to apply consecutively and can therefore quickly disinfect recolonized surfaces to prevent SSI. Based on its high energy, far-UVC radiation has the advantage of inactivating pathogens through the immediate generation of DNA lesions without provoking bacterial resistance. Unlike UVC radiation of 254 nm, which is mostly applied for the disinfection of water and surfaces, it is absorbed strongly in the non-nucleated stratum corneum limiting the penetration of far-UVC photons into the viable epidermis. In this thesis, a novel LED emitting far-UVC light of 233 nm was comprehensively assessed for its skin compatibility evaluating the formation of DNA damage and free radicals on various skin models. Microbiocidal doses as previously determined by project partners of the University Medicine Greifswald were applied. At an application dose from 40 to 60 mJ/cm2, a complete eradication of methicillin-resistant Staphylococcus aureus (MRSA) on agar plates and germ carriers was observed. Irradiation with microbiocidal 233 nm far-UVC led to a minor development of DNA damage in intact ex vivo human skin compared to 10% of a minimal erythema dose (MED) of UVB radiation. Moreover, the formation of free radicals was lower than for visible and near-infrared (VIS–NIR) irradiation equivalent to 20 min solar exposure in reconstructed human epidermal models. To investigate whether 233 nm far-UVC radiation can also be applied to wounds during surgical procedures, an ex vivo wound model was assessed in the follow-up study. An increase and relocation of DNA lesions to deeper areas of wounded skin was observed after irradiation with 233 nm far-UVC. Interestingly, applying artificial wound exudate to the exposed viable epidermis before irradiation led to reconstruction of the photoprotective function of an intact stratum corneum. Furthermore, it was found that a certain amount of free radicals is generated in wounded skin, which is an interesting subject for future studies on possible wound healing processes. To determine the influence of the melanin concentration, human skin of different skin types was irradiated ex vivo with 222 nm, 233 far-UVC light and with broadband UVB light. In this study it was revealed that the formation of DNA lesions was lower in dark skin types than in fair skin types after irradiation at 233 nm. However, 222 nm radiation caused no skin type-dependent differences due to its limited penetration depth while UVB caused a strong divergence between light and dark skin types when applying 10% of a MED. The melanin concentration differs less between light and dark skin types in the upper epidermal fraction than in the deep layers of the epidermis. This leads to skin type-dependent deviations in tolerability due to the maximum penetration depth of the respective wavelength.
In summary, the nanoparticle-based approach for skin decolonization is usefully complemented by the far-UVC light-based approach, and both bear potential for a preoperative and intraoperative skin antisepsis. Nevertheless, the pharmaceutical side requires significant optimization before it can be finally implemented. The use of far-UVC LEDs for skin surface decontamination has been comprehensively addressed for the first time but still further risk assessment studies need to be performed for the final implementation of this approach
Development of an explainable AI system using routine clinical parameters for rapid differentiation of inflammatory conditions
No full textIntroduction: Inflammatory conditions in patients have various causes and
require different treatments. Bacterial infections are treated with antibiotics,
while these medications are ineffective against viral infections. Autoimmune
diseases and graft-versus-host disease (GVHD) after allogeneic stem cell
transplantation, require immunosuppressive therapies such as glucocorticoids,
which may be contraindicated in other inflammatory states. In this study, we
employ a combination of straightforward blood tests to devise an explainable
artificial intelligence (XAI) for distinguishing between bacterial infections, viral
infections, and autoimmune diseases/graft-versus-host disease.
Patients and methods: We analysed peripheral blood from 80 patients with
inflammatory conditions and 38 controls. Complete blood count, CRP analysis,
and a rapid flow cytometric test for myeloid activation markers CD169, CD64,
and HLA-DR were utilized. A two-step XAI distinguished firstly with C5.0 rules
pruned by ABC analysis between controls and inflammatory conditions and
secondly between the types of inflammatory conditions with a new bivariate
decision tree using the Simpson impurity function.
Results: Inflammatory conditions were distinguished using an XAI, achieving an
overall accuracy of 81.0% (95%CI 72 – 87%). Bacterial infection (N = 30), viral
infection (N = 26), and autoimmune diseases/GVHD (N = 24) were differentiated
with accuracies of 90.3%, 80.0%, and 79.0%, respectively. The most critical
parameter for distinguishing between controls and inflammatory conditions was
the expression of CD64 on neutrophils. Monocyte count and expression of CD169
were most crucial for the classification within the inflammatory conditions.
Conclusion: Treatment decisions for inflammatory conditions can be effectively
guided by XAI rules, straightforward to implement and based on promptly
acquired blood parameters.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
The devil is in the detail: Environmental variables frequently used for habitat suitability modeling lack information for forest-dwelling bats in Germany
No full textIn response to the pressing challenges of the ongoing biodiversity crisis, the protection
of endangered species and their habitats, as well as the monitoring of invasive species
are crucial. Habitat suitability modeling (HSM) is often treated as the silver bullet to
address these challenges, commonly relying on generic variables sourced from widely
available datasets. However, for species with high habitat requirements, or for mod-
eling the suitability of habitats within the geographic range of a species, variables at
a coarse level of detail may fall short. Consequently, there is potential value in con-
sidering the incorporation of more targeted data, which may extend beyond readily
available land cover and climate datasets. In this study, we investigate the impact of
incorporating targeted land cover variables (specifically tree species composition) and
vertical structure information (derived from LiDAR data) on HSM outcomes for three
forest specialist bat species (Barbastella barbastellus, Myotis bechsteinii, and Plecotus
auritus) in Rhineland-Palatinate, Germany, compared to commonly utilized environ-
mental variables, such as generic land-cover classifications (e.g., Corine Land Cover)
and climate variables (e.g., Bioclim). The integration of targeted variables enhanced
the performance of habitat suitability models for all three bat species. Furthermore,
our results showed a high difference in the distribution maps that resulted from using
different levels of detail in environmental variables. This underscores the importance
of making the effort to generate the appropriate variables, rather than simply relying
on commonly used ones, and the necessity of exercising caution when using habitat
models as a tool to inform conservation strategies and spatial planning efforts.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg