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    Effect of gloved hand disinfection on hand hygiene before infection-prone procedures on a stem cell ward

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    Background: Hand hygiene compliance even before infection-prone procedures (indication 2, ‘before aseptic tasks’, according to the World Health Organization (WHO)) remains disappointing. Aim: To improve hand hygiene compliance by implementing gloved hand disinfection as a resource-neutral process optimization strategy. Methods: We performed a three-phase intervention study on a stem cell transplant ward. After baseline evaluation of hand hygiene compliance (phase 1) gloved hand disinfection was allowed (phase 2) and restricted (phase 3) to evaluate and differentiate intervention derived from learning and time effects. The incidence of severe infections as well as of hospital-acquired multidrug-resistant bacteria was recorded by active surveillance. Findings: Hand hygiene compliance improved significantly from 50% to 76% (P < 0.001) when gloved hand disinfection was allowed. The biggest increase was for infection-prone procedures (WHO 2) from 31% to 65%; P < 0.001. Severe infections decreased by trend (from 6.0 to 2.5 per 1000 patient-days) whereas transmission of multidrug-resistant organisms was not affected. Conclusion: Gloved hand disinfection significantly improved compliance with the hand hygiene, especially in activities relevant to infections and infection prevention. Thus, this process optimization may be an additional, easy implementable, resource-neutral tool for a highly vulnerable patient cohort.2025-04-0

    Clinical evaluation of monolithic zirconia crowns luted with two different resin cements: 6-month results

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    Zirconia is often used for the fabrication of single crowns (SCs) and other fixed dental prostheses (FDPs) due to its mechanical properties, aesthetics, and excellent biocompatibility (Barão et al. 2010; Manicone et al. 2007; Miyazaki et al. 2013). In several clinical studies zirconia-based SCs show comparable survival and success rates to metal-ceramic FDPs (Pjetursson et al. 2018; Rinke et al. 2016; Sailer et al. 2015; Vigolo und Mutinelli 2012). However, due to its high opacity, veneering with less solid feldspar or glass ceramics is necessary to achieve an aesthetically pleasing overall result (Urapepon und Taenguthai 2015). Similar to metal-ceramic FDPs chipping of the veneering ceramic represents the majority of the technical complications in veneered zirconia FDPs (Schley et al. 2010; Wolfart et al. 2009). To overcome this problem the use of monolithic zirconia FDPs has been introduced. Since there is no need for space of the veneering material only minimal tooth reduction is required (Nakamura et al. 2015). Additionally, the absence of the veneer drastically reduces the occurrence of chipping (Bomicke et al. 2017; Sulaiman et al. 2020; Waldecker et al. 2022). A distinction is now made between four generations of zirconium oxide, which differ in their yttrium content and the addition of aluminum oxide. An increasing yttrium content results in an increase in translucency with a simultaneous reduction in flexural strength (Kolakarnprasert et al. 2019). To address this conflict of objectives, new multilayer materials are being developed that mimic the translucency and color gradient of natural teeth through a hybrid structure while still maintaining good mechanical properties (Pereira et al. 2018; Ueda et al. 2015). Although high-strength materials like zirconia can be luted conventionally the highest bond strength can only be achieved using resin cements (Blatz et al. 2018; Hill und Lott 2011). Similar to adhesive systems used for bonding direct dental restorations, resin cements also come with different application protocols (Perdigao 2020). Some resin cements require the use of an additional adhesive system while others function self-adhesive without any additional steps (Ferracane et al. 2011; Scotti et al. 2017). Adhesive systems that are used in self-etch mode (SE) are often associated with a lower incidence of postoperative hypersensitivity compared to systems that require the use of phosphoric acid as an etching agent. This is thought to be due to the stronger corrosive effect of the phosphoric acid (30%-40%) used in the total-etch (TE) approach (Blatz et al. 2013; Shetty et al. 2012; Yousaf et al. 2014). While various clinical studies suggest that there is no difference in the occurrence of postoperative hypersensitivity between SE and TE adhesive systems for bonding direct restorations (Bekes et al. 2007; Javed et al. 2024; Perdigao et al. 2003; Yamauchi et al. 2019) there is still very limited data comparing both approaches for bonding FDPs. Furthermore, despite the wide use of multi-layered zirconia systems there are very few clinical trials on long-term performance. Therefore, the objective of this study was to evaluate the survival and success of monolithic SCs manufactured with most recent multi-layered zirconia systems and luted with a self-adhesive resin cement and a resin cement using the TE approach. The null hypothesis was that monolithic zirconia SCs show no significant difference in survival and success using the two different luting protocols. It was also assessed if the clinical outcome is influenced by the position of the restoration (anterior versus posterior) or the practitioner (dental student versus dentist).2025-05-2

    Computational Complexity Meets Statistical Efficiency: From Change Point Estimation to Monotonicity Testing

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    CRC 1456 and FOR 5381In the Information Age, statistical efficiency and computational tractability have become equally important. In this dissertation, we propose two novel statistical procedures: the Fast and Optimal Monotonicity Test (FOMT) for the monotonicity testing problem and the Multiscale Quantile Segmentation Controlling Local Error (MUSCLE) for change point detection. FOMT employs a sparse collection of \emph{local} tests, strategically generated at random, to detect violations of monotonicity scattered throughout the domain of the regression function. This sparsity enables significant computational efficiency, achieving sublinear runtime in most cases, and quasilinear runtime (i.e., linear up to a log factor) in the worst case. In contrast, existing statistically optimal tests typically require at least quadratic runtime. FOMT's statistical accuracy is achieved through the precise calibration of these local tests and their effective combination, ensuring both sensitivity to violations and control over false positives. More precisely, we show that FOMT separates the null and alternative hypotheses at minimax optimal rates over Hölder function classes of smoothness order in (0,2](0,2]. Further, when the smoothness is unknown, we introduce an adaptive version of FOMT, based on the Lepskii principle, which attains statistical optimality and meanwhile maintains the same computational complexity as if the intrinsic smoothness were known. MUSCLE partitions serial data into multiple segments, each sharing a common quantile. It leverages multiple tests for quantile changes over different scales and locations, and variational estimation. Unlike the often adopted global error control, MUSCLE focuses on local errors defined on individual segments, significantly improving detection power in finding change points. Meanwhile, due to the built-in model complexity penalty, it enjoys the finite sample guarantee that its false discovery rate (or the expected proportion of falsely detected change points) is upper bounded by its unique tuning parameter. Further, we obtain the consistency and the localization error rates in estimating change points, under mild signal-to-noise-ratio conditions. Both match (up to log factors) the minimax optimality results in the Gaussian setup. All theories hold under the only distributional assumption of serial independence. Incorporating the wavelet tree data structure, we develop an efficient dynamic programming algorithm for computing MUSCLE.2025-04-1

    Die prädiktive Aussagekraft von BNP und NT-pro BNP für Vorhofflimmern bei Patienten über 75 Jahren in der Primärversorgung (Daten der SCREEN-AF Studie)

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    Das zu den supraventrikulären Herzrhythmusstörungen gehörende Vorhofflimmern (VHF) ist eine Erkrankung des älteren Menschen und eine häufige Ursache für einen ischämischen Schlaganfall. Aufgrund des meist asymptomatischen und paroxysmalen Verlaufs gestaltet sich die frühzeitige VHF-Diagnostik in der Primärversorgung als schwierig. Ein systematisches Screening von VHF-Risikokollektiven ist gemäß aktuellem Forschungsstand umstritten. Kardiale Biomarker wie natriuretische Peptide könnten dazu beitragen, Screening-Strategien effizienter zu gestalten. Mit der vorliegenden Studie sollte untersucht werden, ob sich die natriuretischen Peptide Brain natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-pro BNP), N-terminal pro atrial natriuretic peptide (NT-pro ANP) und Mid-regional pro atrial natriuretic peptide (MR-pro ANP) als Prädiktoren für VHF in der Primärversorgung eignen. Die Substudie „Natriuretische Peptide und Prädiktion von Vorhofflimmern“ wurde im Rahmen der internationalen, randomisierten und kontrollierten klinischen SCREEN-AF Studie durchgeführt. Über einen Zeitraum von zwei Jahren (12/2017 bis 03/2019) wurden Patienten über 75 Jahre mit einem arteriellen Hypertonus jedoch ohne bekannten VHF in die Studie eingeschlossen. Bei den Teilnehmern der Interventionsgruppe erfolgte das VHF-Screening über ein Rhythmus-Pflaster zur Langzeit-EKG-Überwachung, das zweimal über zwei Wochen getragen wurde. Teilnehmer der Kontrollgruppe erhielten eine einmalige pulspalpatorische Untersuchung und folgend eine Standardversorgung. Die Plasmaspiegel der natriuretischen Peptide wurden beim Studieneinschluss bestimmt. Der primäre klinische Endpunkt war ein Neuauftreten eines VHF innerhalb des Beobachtungszeitraums von sechs Monaten. Insgesamt wurden bei 291 Teilnehmern Blutproben ausgewertet. Bei acht Teilnehmern wurde ein VHF identifiziert (n = 1 persistierend, n = 7 paroxysmal). Die VHF-Detektionsrate betrug somit 2,7 % (8/291). In der Interventionsgruppe lag die VHF-Detektionsrate bei 4,9 % (7/143) und in der Kontrollgruppe bei 0,7 % (1/148). Studienteilnehmer mit VHF zeigten im Vergleich zu Studienteilnehmern ohne VHF signifikant höhere Plasmaspiegel der natriuretischen Peptide (BNP 78 vs. 41 ng/L (p = 0,012), NT-pro BNP 273 vs. 186 ng/L (p = 0,029), NT-pro ANP 4,4 vs. 3,5 nmol/L (p = 0,027), MR-pro ANP 164 vs. 125 pmol/L (p =0,016)). In der ROC-Analyse zeigten die natriuretischen Peptide BNP und NT-pro BNP bei einer Sensitivität von 100 % die niedrigsten 1-Spezifitätswerte und damit die höchste Spezifität. Die Befunde der Substudie der SCREEN-AF Studie belegen, dass ein systematisches VHF-Screening mittels einer zweimaligen Langzeit-EKG-Überwachung über jeweils 14 Tagen einer pulspalpatorischen Einzelpunkt-Untersuchung und Standardversorgung hinsichtlich der VHF-Detektion überlegen ist. Die natriuretischen Peptide BNP und NT-pro BNP (in geringerem Maße auch MR-pro ANP) eignen sich als Prädiktoren für die Identifikation von Risikopatienten, die von einer längerfristigen EKG-Überwachung profitieren könnten. In Zukunft sollten diese Befunde in umfassenderen Studien validiert werden.Atrial fibrillation (AF) is a common supraventricular arrhythmia that predominantly affects older adults, constituting a significant risk factor for ischemic stroke. Its frequent asymptomatic and paroxysmal presentation makes early detection difficult, particularly in primary care settings. While the clinical utility of systematic AF screening in high-risk populations is unclear, there is emerging evidence to suggest that cardiac biomarkers, specifically natriuretic peptides, may improve the efficacy of targeted screening strategies. This substudy, titled 'Natriuretic Peptides and the Prediction of Atrial Fibrillation', was conducted as part of the international, randomised, controlled SCREEN-AF trial. Between December 2017 and March 2019, individuals aged 75 years or older with a history of arterial hypertension but no prior diagnosis of AF were recruited. Participants assigned to the intervention group underwent prolonged ECG monitoring using a rhythm patch applied for two 14-day periods. The control group received a one-time pulse palpation, followed by standard clinical care. Baseline plasma levels of brain natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), N-terminal pro-atrial natriuretic peptide (NT-proANP) and mid-regional pro-atrial natriuretic peptide (MR-proANP) were measured. The primary endpoint was a diagnosis of AF within the six-month follow-up period. A total of 291 participants provided blood samples for analysis. Atrial fibrillation (AF) was newly diagnosed in eight individuals (2.7%), comprising one case of persistent AF and seven cases of paroxysmal AF. The detection rate was significantly higher in the intervention group (4.9%; seven out of 143) than in the control group (0.7%; one out of 148). Participants with AF exhibited significantly higher baseline concentrations of natriuretic peptides: BNP: 78 vs. 41 ng/L (p = 0.012); NT-proBNP: 273 vs. 186 ng/L (p = 0.029); NT-proANP: 4.4 vs. 3.5 pmol/L (p = 0.027); and MR-proANP: 164 vs. 125 pmol/L (p = 0.016). Receiver operating characteristic (ROC) curve analyses showed that BNP and NT-proBNP had the greatest specificity, as demonstrated by their low 1-specificity values at a sensitivity threshold of 100%. These findings suggest that repeated long-duration ECG monitoring (with a 14-day patch applied twice) is more effective than single-time-point pulse palpation and standard care for detecting AF in older individuals with hypertension. Furthermore, elevated levels of BNP and NT-proBNP, and to a lesser extent MR-proANP, may serve as valuable biomarkers for identifying individuals at an increased risk of AF who could benefit from more intensive rhythm surveillance. These preliminary results highlight the need for larger, prospective trials to validate and refine biomarker-guided screening strategies in primary care.2025-06-2

    C-H Bond Activation by Iridium(III) and Iridium(IV) Oxo Complexes

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    C−H activation by two isostructural, terminal iridium(III) and iridium(IV) oxo complexes is compared. While the driving forces for hydrogen abstraction are almost identical due to compensating contributions from H+ and e− transfer, significant differences in hydrogen tunneling were observed. Increased tunneling for the iridium(III) oxo complex is attributed to its higher basicity, which leads to a narrower potential energy barrier. Our results provide guidelines to steer C−H activation under tunneling control2025-06-1

    Visualization of neutrophil granulocytes and NETs (neutrophil extracellular traps) with expansion microscopy

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    Neutrophil granulocytes are short-lived immune cells which play a significant role in the innate immune system. They are the most abundant immune cell type in the blood as well as part of the first line of defence of the body against pathogens. With the discovery of neutrophil extracellular traps (NETs) in 2004, neutrophil granulocytes became a focus in biomedical research, as NETs appear to be involved in a plethora of malignant, cardiovascular, autoimmune and chronic inflammatory diseases. Understanding neutrophil function and morphology could yield novel therapeutic approaches in the above-mentioned illnesses. Moreover, neutrophils possess unique properties that enable them to quickly migrate to the site of inflammation. In particular, nuclear morphology and biomechanics appear to be crucial to many immune defence functions. In spite of the obvious importance of neutrophil cellular morphology and nuclear composition, studying nuclear functions and morphology remains difficult as they require high-resolution imaging up to super-resolution, which is technically challenging and costly. This dissertation shows an efficient method to analyse single-cell organelles such as the nucleus by expansion microscopy, achieving an 4-5 higher resolution. Expansion microscopy is based on linking labelled epitopes to a polymer, which is then expanded in a swelling process. Combining this method with conventional fluorescence microscopy or confocal microscopy yields very specific information about cellular structures at higher resolution. This method was used in this dissertation to image typical neutrophil markers such as myeloperoxidase and to study the distribution of lamins within the nuclear envelope of neutrophils. Furthermore, we characterized neutrophil chromatin composition in unstimulated cells and in neutrophils undergoing NETosis and analysed heterogeneity of microdomains within the nucleus. In conclusion, expansion microscopy is an useful tool to image neutrophils but also other immune cells with ultra-high resolution to reveal novel aspects of their biology.2025-04-1

    Study on the effect of mouth and nose protection on oral health

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    Zusammenfassung Ziel dieser unizentrischen, randomisierten, explorativen und kontrollierten Cross- over-Beobachtungsstudie war es, den Einfluss der Stoff-, medizinischen- und FFP2-Masken auf die Speichelparameter und das Auftreten von Halitosis anhand objektiv messbarer Parameter zu untersuchen und die Ergebnisse mit der Kontrolle „ohne Maske“ zu vergleichen. Freiwillige, gesunde Proband*innen (n = 39, 31,8 ± 13,7 Jahre) gaben an vier Versuchstagen jeweils morgens und nach einer vierstündigen Tragezeit einer Stoff-, medizinischen-, FFP2-Maske bzw. vier Stunden ohne Maske unstimulierten und stimulierten Speichel ab. Im gleichen zeitlichen Ablauf wurde darüber hinaus die Konzentration der flüchtigen Schwefelverbindungen mit einem Halimeter® gemessen. Daraufhin wurden verschiedene Parameter (Speichelfließrate, pH-Wert, Pufferkapazität) des stimulierten und unstimulierten Speichels bestimmt. Die statistische Auswertung erfolgte mittels einfaktorieller ANOVA mit Messwiederholung (p<0,05). Die verschiedenen Maskenarten (Stoff-, medizinische-, FFP2-Maske) und die Kontrolle ohne Maske repräsentierten die Innersubjektfaktoren. Es konnten keine signifikanten Effekte beim Tragen der verschiedenen Masken hinsichtlich der Speichelfließrate, des pH-Werts und der Pufferkapazität des stimulierten und unstimulierten Speichels und der VSC-Konzentration nach einer vierstündigen Tragezeit festgestellt werden. Hinsichtlich der VSC- Konzentrationen konnte eine Tendenz zu erhöhten Halitosis-Werten beobachtet werden, die statistisch jedoch nicht signifikant waren. Diese Studie stellte somit keine signifikante Beeinflussung der untersuchten Speichelparameter und der Konzentrationen flüchtiger Schwefelverbindungen durch das Tragen verschiedener MNS fest.Abstract The aim of this single-center, randomized, exploratory and controlled cross-over observational study was to investigate the influence of cloth, medical and FFP2 masks on saliva parameters and the occurrence of halitosis using objectively measurable parameters and to compare the results with the control “without mask”. On four test days, healthy volunteers (n = 39, 31.8 ± 13.7 years) released unstimulated and stimulated saliva in the morning and after wearing a cloth, medical or FFP2 mask for four hours or four hours without a mask. The concentration of volatile sulphur compounds was also measured at the same time using a Halimeter®. Various parameters (saliva flow rate, pH value, buffer capacity) of the stimulated and unstimulated saliva were then determined. Statistical analysis was performed using a single-factor ANOVA with repeated measures (p<0.05). The different mask types (cloth, medical, FFP2 mask) and the control without mask represented the within-subject factors. No significant effects were observed when wearing the different masks in terms of saliva flow rate, pH value and buffer capacity of stimulated and unstimulated saliva and VSC concentration after a four-hour wearing period. With regard to the VSC concentrations, a trend towards increased halitosis values was observed, although this was not statistically significant. This study therefore found no significant influence on the saliva parameters examined and the concentrations of volatile sulphur compounds by wearing different MNS.2025-05-1

    Characterisation of exoplanet atmospheres with high-resolution spectroscopy

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    Hochauflösende spektroskopische Beobachtungen ermöglichen die Untersuchung der Zusammensetzung und Dynamik von exoplanetaren Atmosphären. Absorptions- und Emissionslinien dienen als wertvolle Diagnostik, da ihre Stärke, Position und Form direkt mit den thermischen, chemischen und dynamischen Bedingungen in der Atmosphäre verbunden sind. Insbesondere die relativ starken spektroskopischen Signale von heißen Jupitern (HJs), einer Klasse heißer Gasriesen mit kurzen Umlaufperioden, bieten die Möglichkeit für detailierte atmosphärische Charakterisierungen. Diese Arbeit präsentiert die Analyse von Transmissions- und Emissionsspektren von vier verschiedenen HJs unter Verwendung der hochauflösenden Spektrographen CRIRES+^+ und CARMENES. Neben dem Nachweis von H2_2O detektieren wir zum ersten Mal CO in der Atmosphäre von WASP-43b und bestimmen darüber hinaus das Temperaturprofil, die chemischen Häufigkeiten und das atmosphärische C/O-Verhältnis. Unsere Analyse zeigt keine eindeutigen Hinweise auf eine Wolkendecke auf der Tagseite des Planeten. Basierend auf der beobachteten Linienverbreiterung bestimmen wir die Geschwindigkeit eines äquatorialen superrotierenden Jet auf 5 km\,s1^{-1}, in Übereinstimmung mit Vorwärtsmodellen und niedrigauflösenden Beobachtungen dieses Planeten. Bei der Untersuchung der des Emissionsspektrums von WASP-189b detektieren wir starke Signaturen von CO und Fe. Durch die Integration eines neuen zweidimensionalen Linienprofil-Modells in unser Retrieval-Framework ermitteln wir die Windeigenschaften und interpretieren beobachtete Geschwindigkeitsdifferenzen. Unsere Analyse deutet auf einen globalen Tag-Nacht-Wind und insbesondere auf die Abwesenheit eines äquatorialen Jets hin. Diese Ergebnisse liefern konkrete Einblicke in die planetare Atmosphärendynamik, und wir diskutieren, wie Winde und andere Effekte zu den Geschwindigkeitdifferenzen beitragen können. Schließlich analysieren wir Transmissionsspektren von WASP-69b und KELT-11b, die mit CARMENES beobachtet wurden, und finden kein eindeutiges Signal für alle untersuchten Spezies. Für beide Planeten werden zwar vorläufige H2_2O-Signale nahe der erwarteten planetaren Geschwindigkeit detektiert, aber wir können den planetaren Ursprung dieser Signale nicht eindeutig verifizieren. Wir verwenden zwei unabhängige Ansätze um zu untersuchen, welche Kombinationen von molekularen Häufigkeiten und Wolkenhöhe zu den beobachteten Signalen und Nicht-Detektionen führen würden. Eine Methode basiert auf Injection-Recovery-Tests, während die zweite Methode ein Retrieval-Framework zur Eingrenzung des Parameterraums verwendet. Wir stellen fest, dass beide Ansätze ähnliche Einschränkungen liefern, die wir mit früheren Studien dieser Planeten vergleichen.High-resolution spectroscopic observations offer a powerful approach to investigate planetary atmospheric composition and dynamics. Absorption and emission spectral lines serve as valuable diagnostics, as their strength, position, and shape are directly connected to the thermal, chemical, and dynamical conditions within exoplanetary atmospheres. Particularly the relatively large spectroscopic signals of hot Jupiters (HJs), a class of hot gas giants with small orbital periods, offer the opportunity for in-depth atmospheric characterisations. This work presents the analysis of transmission and emission spectra of four different HJs using the high-resolution spectrographs CRIRES+^+ and CARMENES. We report the first detection of CO and evidence for the presence of H2_2O in the dayside atmosphere of WASP-43b, and further retrieve the temperature profile, chemical abundances, and atmospheric C/O ratio. Our analysis revealed no conclusive evidence of a cloud deck on the planet's dayside. Based on the observed line broadening, we retrieve an equatorial super-rotating jet with a wind speed of 5 km\,s1^{-1}, in agreement with forward models and low-resolution observations of this planet. Examining WASP-189b's dayside emission, we detect strong signatures of CO and Fe. By integrating a novel two-dimensional wind-induced line profile model with our retrieval framework, we retrieve wind properties and interpreted observed velocity offsets. Our analysis suggest a global day-to-night wind circulation pattern and notably the absence of an equatorial jet. These results provide nuanced insights into planetary atmospheric dynamics, and we discuss how winds and other effects can contribute to the velocity offsets. Lastly, we analyse transit observations of WASP-69b and KELT-11b observed with CARMENES, and find no clear signal for any of the investigated species. While tentative H2_2O signals are detected close to the expected planetary rest frame for both planets, we can not unambiguously confirm the planetary origin of these signals. We employ two independent approaches to investigate, which combinations of molecular abundances and cloud height would result in the observed tentative signals and non-detection. One method is based on injection-recovery tests, while the other method applies a retrieval framework to constrain the parameter space. We find that both approaches generally provide similar constraints, which we compare to previous studies of these planets.2025-03-1

    Oxygen flux simulations as a constraint for carbon fluxes and nitrogen sources in a temperate forest ecosystem

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    The O2:CO2 exchange ratio (ER) between terrestrial ecosystems and the atmosphere is a key parameter for partitioning global ocean and land carbon fluxes. The long-term terrestrial ER is considered to be close to 1.10 mol of O2 consumed per mole of CO2 produced. Due to the technical challenges in measuring directly the ER of entire terrestrial ecosystems (EReco), little is known about variations in ER at hourly and seasonal scales, as well as how different ecosystem and flux components (e.g., vegetation and soil, assimilation and respiration) contribute to EReco. In this modeling study, we explored the variability in and drivers of EReco and evaluated the hypothetical uncertainty in determining ecosystem O2 fluxes based on current instrument precision used in micrometeorological methods such as the flux-gradient approach. We updated the one-dimensional, multilayer atmosphere–biosphere gas exchange model “CANVEG” by 1) implementing ER for various ecosystem components in the model; 2) implementing the control of triose phosphate utilization (TPU) and Medlyn’s stomatal conductance equation to CO2 assimilation; and 3) linking photosynthetic O2 emission to nitrogen (N) assimilation sources. The model study was conducted at the Leinefelde FLUXNET site, a temperate beech forest in Germany, where eddy-covariance, profile, and gas exchange chamber measurements were available. We found that when assuming fixed ER for CO2 assimilation and respiration, the hourly EReco showed strong variations over diel and seasonal cycles and within the vertical canopy profile, indicating the potential to partition eddy-covariance derived CO2 fluxes with corresponding O2 flux measurements. The O2 and CO2 mole fraction ratio of canopy air (ERconc) showed different values and mechanisms from EReco. The model showed more robust performances in future CO2, temperature and air humidity conditions when taking into account TPU limitation and Medlyn’s stomatal conductance algorithm in CO2 assimilation processes. The predicted net carbon sink under elevated atmospheric CO2 mole fraction increased less with TPU limitation than without. The most significant impacts on photosynthetic O2 emission and hence the ER of CO2 assimilation resulted from variation in nitrogen assimilation sources. The ER of net photosynthetic O2 and CO2 exchange measured with branch-level gas exchange chambers 2 showed little variation from 1.0 mol mol-1, indicating ammonia as the main N assimilation source. But O2 emission would increase by up to 11% if the fraction of nitrate increases in the N assimilation source. Our study successfully coupled oxygen with carbon fluxes within a multilayer atmosphere–biosphere gas exchange model. The modeling study yielded that the application of the flux-gradient measurement approach is feasible to derive ecosystem O2 fluxes. To achieve better model behavior, it is necessary to incorporate TPU limitation in the assimilation model and to properly consider N assimilation during photosynthesis.2025-04-1

    Developing tools for translational In-vivo cochlear optical stimulation

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    Utilizing optogenetic stimulation to target type I spiral ganglion neurons (SGNs) could promise an alternative to the currently employed electrical stimulation by current cochlear implants (CIs). Given light's spatial confinement capabilities, the future optical cochlear implant (oCI) holds the promise of substantially increasing independently perceived stimulation channels. To date, the optogenetic modification of adult SGNs was performed by injection of a viral vector directly into the modiolus. However, this poses some challenges in achieving efficient SGN transduction, such that only a small fraction of injected animals responded positively to light stimulation. Additionally, it has remained demanding to quantify the fraction of transduced SGNs from the thousands present in the cochlea. This thesis aims to provide tools for the advancement of cochlear optogenetics in mature animals via two main objectives: i) enhancing the efficacy of viral delivery compared to the previous modiolus approach, ii) investigating methods to automate segmentation of SGNs in images obtained from light sheet microscopy (LSM). This study reveals that catheter-based administration via round window insertion along with the vent at the oval window (RW + OW vent) is the most reliable viral delivery method in mature gerbil cochleae. The RW + OW vent approach achieved an 80% success rate in eliciting auditory brainstem responses to light (oABRs), notably surpassing the 40% success rate obtained from the modiolus approach. Similar results were observed even in deafened cochlea without functioning inner hair cells (IHCs), which resemble the scenario of sensorineural hearing loss. The study also suggests that off-target IHC transduction correlates with longer response times, particularly at lower light intensities. Furthermore, this work explores pipelines for SGN segmentation in volumetric 3D images of intact cochleae from light sheet microscopy. Initially, a watershed-based algorithm using Arivis Vision 4D software showed promise for semi-automatic segmentation. While this approach showed promising results, it required substantial manual labor to refine the process. A subsequent implementation of a Python-based deep learning algorithm, StarDist, demonstrated potential for more precise and faster segmentation. This study provides a foundation for future advancements in preclinical cochlear optogenetics by addressing the challenges in optimization in terms of viral delivery into the cochlea and automatic SGN segmentation.2025-01-1

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