Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
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Structure-Property Relationships of Waterborne Polyurethane Dispersions based on Novel Hybrid Components
Get PDFWater-based polyurethane hybrid dispersions (PUHD) are becoming increasingly important in technical applications in the coatings and adhesives industry. These are aqueous PU mixing systems consisting of polyurethane (PU) and other polymeric materials such as acrylate, silicone or fluorine compounds. The result is an improved material performance in respect to the basic PU products, such as mechanical properties, and a good alternative to the usual post-curing with additives required for PUD films. Nevertheless, hybrid synthesis (miniemulsion polymerization, grafting) poses great challenges.
The focus of this work is on the synthesis of the hybrid component and its incorporation into the PU framework. Polystyrene (PS) disclose a particularly interesting range of properties due to its high glass transition temperature (Tg). Properties such as segregation phenomena, uncontrolled PS content, molecular weight (Mn) and other negatively influencing parameters due to lack of covalent bonding are circumvented by targeted covalent incorporation of PS blocks into the PU scaffold and should provide insights into structural effects that significantly influence film properties.
For this purpose, bifunctional polystyrene (PS(OH)2) is used in the PU reaction. Living polymerization techniques are suitable for the production of such components with tailor-made hydroxyl functionalities. In particular, the Radical Addition Fragmentation Transfer (RAFT) process is one such technique. A new effective RAFT agent based on trithiocarbonate has been kinetically investigated. As a valuable alternative, anionic polymerization initiated with lithium naphtalenide (LiNaph) and terminated with propylene oxide (PO) has been inves-tigated. The optimal reaction conditions of both methods are highlighted, and the PS(OH)2 obtained is extensively characterized. A correlation between Mn and Tg is confirmed. The prepolymer reaction as an essential building block of PUHD synthesis is investigated with respect to the PS(OH)2 content. Both synthesis processes yield polyols with good reactivity towards isocyanates.
Finally, the preparation of corresponding PUHDs by the acetone process is investigated. Practical formulations are used. Both PS(OH)2 types are varied according to their content in the dispersion and structure-property effects are studied. It is found that the PS blocks are fully incorporated into the PU framework. A maximum amount of PS(OH)2 is still required to optimize the properties of both components in the PUHD.
Overall, the structure-property relationships of PUHDs and their potential interactions are covered in this work. The knowledge gained can be used to specifically optimize formulations and manufacturing processes. Furthermore, PUHDs systems based on other hybrid components, such as acrylate diols, can also benefit from the findings of this work
Vergleich der Lebensqualität von Kindern mit Zöliakie gegenüber Kindern mit chronisch entzündlichen Darmerkrankungen – Eine Befragung betroffener Kinder und deren Eltern
No full textKinder und Jugendliche (im Folgenden als Kinder bezeichnet) mit Zöliakie und chronisch entzündlichen Darmerkrankungen (CED) (M. Crohn, Colitis ulcerosa, Colitis indeterminata) stellen einen wichtigen Teil der Patienten der kindergastroenterologischen Abteilungen dar.
In ihrem Alltag sind die Patienten oftmals mit Einschränkungen konfrontiert. So existiert für an Zöliakie erkrankte Kinder als einzige Therapieoption nur eine lebenslange, strikte glutenfreie Ernährung.
Kinder mit CED hingegen können belastet sein durch wiederkehrende Krankheitsschübe und resultierende körperliche Beschwerden sowie eine regelmäßige Medikamenteneinnahme.
Ziel dieser Studie war es daher, mittels Fragebögen die Lebensqualität beider
Patientengruppen durch Befragung der Kinder und ihrer Eltern zu erheben. Darüber hinaus sollte ermittelt werden, ob sich die Lebensqualität beider Gruppen unterscheidet und, ob krankheitsspezifische schwerpunktmäßig beeinträchtigte Bereiche der Lebensqualität existieren. Als möglicher Risikofaktor wurde zudem der Einfluss klinischer und demografischer
Variablen auf die Lebensqualität untersucht. Darüber hinaus analysierten wir die Eltern-Kind-Übereinstimmung hinsichtlich der angegebenen Lebensqualität und ordneten unsere Studienergebnisse in den Kontext veröffentlichter Daten zur Lebensqualität von gesunden und gastrointestinal erkrankten Kindern ein.
Die Datenerhebung erfolgte im Rahmen einer monozentrischen, prospektiven Studie in der kindergastroenterologischen Abteilung der Universitätskinderklinik Köln. Zwei validierte Fragebögen wurden zur Erfassung der allgemeinen Lebensqualität (Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales Short Form 15) und der symptombezogenen Lebensqualität (Pediatric Quality of Life Inventory™ 3.0 Gastrointestinal Symptoms Scales) genutzt. Kinder zwischen 3 und 18 Jahren und ihre Eltern nahmen an der Studie teil und
insgesamt wurden die Fragebögen von 220 Teilnehmern ausgewertet (119 Patientenfälle; davon Zöliakie: n = 67; CED: n = 52).
Es zeigte sich eine gute Gesamtlebensqualität beider Gruppen, die untereinander vergleichbar war und auch im Eltern-Kind-Vergleich keine signifikanten Unterschiede aufwies. Kinder mit Zöliakie zeigten jedoch eine niedrigere Lebensqualität im Hinblick auf Essenseinschränkungen
(p < 0.01), Reflux und Sodbrennen (p < 0.01), Schluckbeschwerden (p = 0.02) und Emotionale Beschwerden (p = 0.04). Kinder mit CED hingegen waren vor allem durch das Vorkommen von Blut im Stuhl in ihrer Lebensqualität beeinträchtigt (p < 0.01). Calprotectin-Werte im Stuhl
zeigten einen signifikanten Zusammenhang mit der Gesamtlebensqualität, die von Kindern mit CED und ihren Eltern angegebenen wurde.
Die allgemeine Lebensqualität unserer Kinder zeigte sich vergleichbar mit der von in der Literatur berichteten gesunden Kindern und besser als jene von in der Literatur berichteten gastrointestinal erkrankten Kindern.
Zusammenfassend zeigt sich, dass Kinder mit Zöliakie und CED trotz ihrer chronischen Erkrankungen eine gute Lebensqualität erreichen können.
Das Fehlen einer vergleichbaren Alters- und Geschlechtsverteilung zwischen beiden Patientengruppen limitiert die Aussagekraft der nachgewiesenen Vergleichbarkeit ihrer Lebensqualität. Gleichwohl liefert die
Studie wertvolle Erkenntnisse über krankheitsspezifisch beeinträchtige Bereiche der Lebensqualität. Größere, multizentrisch durchgeführte Studien müssen folgen, um generalisierbare Erkenntnisse zu gewinnen
Signatures of Perseveration and Heuristic-Based Directed Exploration in Two-Step Sequential Decision Task Behaviour
No full textProcesses formalized in classic Reinforcement Learning (RL) theory, such as model-based (MB) control and exploration strategies have proven fertile in cognitive and computational neuroscience, as well as computational psychiatry. Dysregulations in MB control and exploration and their neurocomputational underpinnings play a key role across several psychiatric disorders. Yet, computational accounts mostly study these processes in isolation. The current study extended standard hybrid models of a widely-used sequential RL-task (two-step task; TST) employed to measure MB control. We implemented and compared different computational model extensions for this task to quantify potential exploration mechanisms. In two independent data sets spanning two different variants of the task, an extension of a classical hybrid RL model with a heuristic-based exploration mechanism provided the best fit, and revealed a robust positive effect of directed exploration on choice probabilities in stage one of the task. Posterior predictive checks further showed that the extended model reproduced choice patterns present in both data sets. Results are discussed with respect to implications for computational psychiatry and the search for neurocognitive endophenotypes
Complexes of Pt(II), Pd(II) and Ni(II) with Ring-Expanded Tridentate Cyclometalated Ligands
No full textIn this work, square-planar complexes [M(L)X] of Pt(II), Pd(II) and Ni(II) with L = tridentate, cyclometalated, so-called ring-expanded ligands were studied. In a first approach, the 8-quinolinyl moiety was used to achieve the ring-expanded, six-membered metallacycle. The complexes with N^C^N or C^N^N binding motives (N = pyridyl or quinolinyl) for the tridentate ligands revealed strong geometric distortions as indicated by single crystal X-ray diffraction. This leads to nearly perfect square planar coordination at the cost of coplanarity and conjugation of the ligand backbones. Spectroscopic data, supported by DFT-calculations revealed a strong influence of the ring-expansion on MLCT absorptions. Preliminary investigations showed promising luminescence results, especially for Ni(II) compounds.
Introduction of further chromophore moieties such as carbazolyl and fluorenyl resulted in even stronger structural distortions of the ligand backbone. UV/Vis-absorption spectroscopy and cyclic voltammetry confirmed carbazole-containing complexes to exhibit strong shifts of MLCT transitions as well as electrochemical potentials, due to the strong σ-donor character of the ligands. Fluorene-containing complexes showed broad UV/Vis-absorptions, but the introduction of the fluorene moiety had little impact on electrochemistry.
Introduction of sulphur and oxygen into the ligand backbones expanded the scope to N^C^S and N^C^O systems. Their complexes feature interesting oxidations of the sulphur-atoms in the ligand backbone and weak coordination of oxygen-donors, prone to exchange with solvent molecules.
Systematic coligand (X) exchange reactions of the [M(L)X] complexes were carried out using the nitrato derivatives [M(L)NO3] as key intermediates. This NO3-coligand was exchanged under very mild conditions, allowing for a wide range of anionic, pseudo-halogenide coligands to be introduced. This method was further adapted to introduce acetylide- or pyrrole-derived coligands, that are strong σ-donors with potential for π-backbonding. These coligands have a large impact on optical and electrochemical properties and the systematic exchange is a potent method for adjusting complex properties.
Overall, this work broadens the portfolio of tridentate ligands for cyclometalated complexes, with ring-expansion opening the way to many new complex species. Their properties can be tailored to specific applications through ligand design with various donors or further tuned by coligand exchange reactions. Future work could see these methods applied towards complexes in luminescent materials and optoelectronic devices
Climate Fiction as Future‐Making: Narrative and Cultural Modelling Beyond Representation
No full textClimate fiction (cli‐fi) increasingly attracts the attention of wider publics and expert science communities. And yet, critiques of its limits and the limits of its efficiency as a tool of persuading broader readerships are also becoming more frequent. This article draws on such critiques and discussions of the limits of representing climate change and related crises. We argue that, first, a focus on the representational capacity of fiction occludes other, equally important, functions of fiction. Second, we aver that such a focus insufficiently reflects on its own didactic bias that leads critics to endorse or even instrumentalize literary narrative for the seemingly obvious good cause of educating or mobilizing readers. The article suggests shifting the focus from mere issues of representation to questions of the effect and impact of reading in the wider conceptual context of climate imaginaries, defined as a shared set of beliefs, practices and norms, that define the scope of individual and collective future‐thinking. It aims to develop a better understanding of the potential links between future‐making and fiction and employs insights from model theory and theories and practices of (climate) modelling—the dominant, authoritative form of future‐making in many disciplines, especially the natural sciences—to propose that cli‐fi can be seen as an important alternative future‐making tool when it is recognized as a form of cultural modelling. This allows us to acknowledge that cli‐fi is a future‐making technology directly impacting climate imaginaries, as the article will show through exemplary readings of two case studies, Jessie Greengrass's novel The High House (2021) and Rory Mullarkey's play Flood (premiered 2018)
Cochrane systematic reviews for national and international evidence-based clinical practice guidelines
No full textBackground
The development of a clinical guideline requires a significant investment of time and financial resources. One potential approach to enhance efficiency is to use systematic reviews to inform the clinical guideline. Cochrane reviews are particularly suitable for this purpose due to their high methodological rigour, quality and independence. A key benefit of a close collaboration between review and guideline authors is to ensure better coordination, which is essential for the smooth progress.
Objective
The objective of this cumulative dissertation is to conduct Cochrane reviews to inform national and international evidence-based clinical practice guidelines.
Methodology
This cumulative dissertation includes four Cochrane reviews, all of which adhere to the rigorous Cochrane methodology. This includes the following steps: title registration, development of the protocol and search strategy, reference screening, data extraction, risk of bias assessment, conducting meta-analyses, Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment, interpretation of the results and publication. The methodology of this dissertation was to incorporate the following Cochrane reviews into clinical practice guidelines.
Project: Corticosteroids for the treatment of coronavirus disease 2019 (COVID-19)
-Systemic corticosteroids for the treatment of COVID-19
-Systemic corticosteroids for the treatment of COVID-19 – Equity-related analyses and update on evidence
-Inhaled corticosteroids for the treatment of COVID-19
Project: Physical exercise interventions for the treatment of cancer-related fatigue
-Cardiovascular training for fatigue in people with cancer
Results
Effects of the interventions
The Cochrane review on systemic corticosteroids, including 11 studies with 8075 participants, showed beneficial effects on all-cause mortality (up to 30 days) and ventilator-free days in people hospitalised for symptomatic COVID-19. However, due to the significant uncertainty in the evidence, no definitive conclusions could be drawn regarding the new need for invasive mechanical ventilation (IMV) and safety outcomes.
The update of this Cochrane review, incorporating 16 studies with 9549 participants, resulted in a positive effect on all-cause mortality (up to 30 days), clinical improvement (discharged alive) and on the combined outcome new need for IMV or death in people hospitalised because of symptomatic COVID-19. There was still considerable uncertainty regarding safety outcomes and all-cause mortality (up to 120 days). The analysis suggested a potential benefit for younger individuals (under 70 years of age) and for Black, Asian, and minority ethnic groups in terms of all-cause mortality (up to 30 days).
For details regarding the Cochrane reviews on inhaled corticosteroids and cardiovascular training, see full text of the dissertation.
Clinical practice guideline recommendations
The following guideline recommendations were formulated on the basis of the Cochrane reviews:
Systemic corticosteroids for the treatment of COVID-19
S3 guideline for inpatient COVID-19 therapy (version 23 February 2021)
Recommendation level: A
Patients with severe (oxygen saturation (SpO2) 30/min) or critical (acute respiratory distress syndrome (ARDS), sepsis, ventilation, vasopressor administration) COVID-19 disease should be treated with dexamethasone.
Systemic corticosteroids for the treatment of COVID-19 – Equity-related analyses and update on evidence
S3 guideline for inpatient COVID-19 therapy (version 05 October 2021)
Recommendation level: A
Patients with COVID-19 and oxygen requirements (low-flow, high-flow, non-invasive ventilation/ continuous positive airway pressure (CPAP), invasive ventilation) should be treated with systemic corticosteroids. Treatment ought to be with 6 mg dexamethasone orally or intravenously for ten days.
Recommendation level: A
Patients with moderate disease (hospitalised without the need for oxygen) should not be treated with systemic corticosteroids.
S3 guideline for inpatient COVID-19 therapy (version 28 February 2022)
Recommendation level: A
Patients with COVID-19 and low-flow/high-flow oxygen requirements or non-invasive/invasive ventilation should be treated with systemic corticosteroids. Treatment ought to be with 6 mg dexamethasone orally or intravenously for ten days.
Recommendation level: A
Patients with mild to moderate disease without the need for oxygen should not be treated with systemic corticosteroids.
S2e guideline for outpatient COVID-19 therapy (version 04 February 2022)
Recommendation level: expert consensus
Systemic corticosteroids should not be used for COVID-19 therapy in outpatient settings.
For details regarding the international guideline recommendations, and the Cochrane reviews on inhaled corticosteroids and cardiovascular training, see full text of the dissertation.
Conclusion
The research projects have shown that Cochrane reviews are an effective way of informing national and international evidence-based clinical practice guidelines. However, for this to work effectively, there needs to be close coordination and cooperation between review and guideline authors. This helps to avoid discrepancies of any kind, for example in the population of interest. Furthermore, close collaboration between clinicians and methodologists facilitates the direct communication of questions that arise in routine clinical practice, ensuring their prompt resolution and addressing in both the review and the guideline. Conversely, queries that arise on the methodological side and require clinical input can be addressed directly to the clinicians, thus facilitating rapid resolution
Distributional equality in Ethereum? On-chain analysis of Ether supply distribution and supply dynamics
No full textBlockchain-based emerging technologies such as decentralized finance (DeFi), cryptocurrencies, tokens, and smart contracts have introduced innovative frameworks for resource allocation and economic interactions. Ethereum, as the major technical network foundation of DeFi and tokenized assets, is becoming increasingly pivotal in facilitating an extension and alternative to traditional finance for many stakeholders, including those who are “unbanked”. Moreover, the recent transition of Ethereum from a proof-of-work (PoW) mechanism to a proof-of-stake (PoS) consensus mechanism and the Shanghai upgrade may significantly impact Ether (ETH) distribution. However, the status quo and dynamics of wealth distribution, especially after these changes in governance structure, remain unclear. By utilizing a rich dataset spanning the entire Ethereum history from July 2015 to December 2024, we analyze the balances across address groups of different sizes and the role of key economic activities and infrastructure components within Ethereum, such as exchanges, DeFi platforms, and staking. To provide detailed insights into ETH’s distributional equality, our approach combines descriptive, longitudinal, and causal inference analyses; a complete enumeration of more than 98 million unique wallet addresses; and novel on-chain analysis. Our findings show a substantial concentration of ETH within a small fraction of addresses, with approximately 0.3% of wallets holding nearly 95% of the total supply, despite the majority of wallets holding less than 0.1% ETH. However, the ETH distribution broadly resembles wealth distributions in traditional economies, with a log-normal body and Pareto-like tails. We assert that previous studies have overstated the concentration of ETH. Additionally, our dynamic analysis reveals a nuanced trend toward less concentration over time, driven by market cycles, increasing staking participation, and reinvestment in DeFi. These results challenge the notion of pervasive centralization. This study contributes to a deeper understanding of the current ETH distribution and its evolution over time. Therefore, this work provides an objective, data-driven basis for the ongoing discussion on wealth (in)equality in blockchain-based ecosystems, particularly in DeFi
