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Die vaskuläre Architektur der makulären Neovaskularisation bei altersbedingter Makuladegeneration als Prädiktor für den Therapiebedarf: eine 3-Jahres-Längsschnittanalyse
No full textBackground: Anti-Vascular Endothelial Growth Factor (VEGF) therapy is an effective therapy for improving and stabilizing the vision of patients with neovascular age-related macular degeneration (nAMD). However, the treatment requirements, particularly the number of intraocular injections, can vary significantly among patients. This study aimed to analyze the vascular characteristics of macular neovascularizations (MNVs) to identify potential biomarkers that could predict the required injection frequency throughout the disease course. Methods: In all patients, the initial diagnosis of nAMD was confirmed using optic coherence tomography (OCT), fluorescein angiography, and OCT angiography (OCTA). MNVs detected using OCTA were subjected to quantitative vascular analysis of their area, total vascular length (sumL), fractal dimension (FD), and flow density. These results were then correlated with the number of intravitreal anti-VEGF treatments administered during the first 3 years of treatment. Additionally, the relationship between the parameters and visual acuity progression was analyzed. Results: A total of 68 treatment-naïve eyes were included in the study, comprising 31 eyes with type 1 MNV, 19 eyes with type 2 MNV, and 18 eyes with type 3 MNV. The average MNV area at baseline was 1.11 mm2 ± 1.18 mm2, the mean total vascular length was 12.95 mm ± 14.24 mm, the mean fractal dimension was 1.26 ± 0.14, and the mean flow density was 41.19 ± 5.87. On average, patients in our cohort received 19.8 ± 8.5 intravitreal injections (IVIs). A significant correlation was found between the number of administered IVIs in the first 3 treatment years and the MNV area (p < 0.005), sumL (p < 0.005), and FD (p < 0.05), while no correlation was found with flow density. Additionally, there was no significant association between MNV type and treatment requirements, nor between MNV vascular architecture and visual acuity progression. Conclusions: The results suggest that the specific vascular structure of untreated MNV may serve as a predictor of long-term treatment demand. With the emergence of new drug classes and advancements in imaging techniques, these parameters could offer valuable insights for forecasting treatment requirements
Pharmacy students’ perceptions of a competency-based subject catalogue for the first state examination in Germany
No full textBroad rim lesions are a new pathological and imaging biomarker for rapid disease progression in multiple sclerosis
No full textCurrent multiple sclerosis (MS) treatments reduce relapse activity but have limited impact on disease progression. Clinical trials targeting progression often fail because of insufficient understanding of its underlying mechanisms. This study analyzed a clinically well-characterized MS autopsy cohort from the Netherland Brain Bank (186 individuals) from which we selected donors exhibiting opposite disease trajectories of slow versus rapid progression. We performed extensive unbiased histology and spatial transcriptomics, which unveiled a distinct MS lesion type marked by an extensive myeloid cell rim with cellular and transcriptional signatures of innate immune activation, inflammatory cytokine production, unfolded protein response and apoptosis. Presence of this particular lesion type was linked to rapid disease progression. An independent translocator protein 18-kDa positron emission tomography study (114 individuals) validates the association between lesions with a broad myeloid cell rim and disease progression in individuals with MS. Our findings offer crucial insights into the mechanisms behind MS progression, identifying broad rim lesions as a biomarker for rapid disease progression and potentially guiding patient selection for future therapeutic trials targeting central nervous system intrinsic inflammation
Investigating various carbon materials as electrochemical sensors for detecting unexploded ordnance in the marine environment
No full textMillions of tons of discarded military munitions and unexploded ordnance (UXO) contaminatethe seas due to large-scale dumping operations after the Second World War.These UXOs pose risks through spontaneous detonations and the release of toxic explosivecompounds as their shells corrode. Their detection and removal are complicated bythe sparse documentation of dumping sites. The electrochemical detection of dissolvedexplosive compounds in seawater offers a promising approach for fast, on-site identificationof corroded UXOs. This thesis investigates the viability of such a sensor andhow the use of graphite, glassy carbon, and screen-printed carbon as working electrodematerial influences the sensitivity and long-term stability of the detection.Using square wave voltammetry, high concentrations of 2,4,6-trinitrotoluene (TNT)could reliably be detected in seawater with all three electrode materials, and the characteristicredox peaks could be identified. A significant challenge was found to be anincrease in background current, which occurred even over short periods of continuousscanning. This increase is likely caused by material loss or surface changes, leading toenhanced surface reactions and non-faradaic effects. The increase was least pronouncedwith the graphite electrode, implying a material-dependent effect. Screen-printed carbonelectrodes showed a loss of functionality due to this, making them unsuitable for prolongedmeasurements in seawater. The graphite and glassy carbon electrodes maintainedtheir functionality and could be restored by manual polishing. Detection of explosivesby identification of the characteristic reduction peaks in background-subtracted scanswas shown to be a promising method for confirming their presence in the environment asit minimizes the influence of the background current. The graphite electrode exhibitedthe lowest detection limit for TNT between 0.44 and 0.88 μmol L 1, which correspondsto concentrations found in close proximity to leaking UXOs. While the detection at longdistances remains challenging due to the effects of material degradation, the findingspresented in this work demonstrate that electrochemical sensors with graphite workingelectrodes are able to detect explosives at relevant concentrations. In contrast to conventionalchemical detection methods, which require sample collection and lab analysis,electrochemical methods could provide fast, on-site detection of corroded UXOs
Silts with a human touch: transition from naturally- to anthropogenically-controlled fluvial dynamics revealed by OSL dating and heavy-metal analysis
No full textWhile the dynamics of central European fluvial systems were originally controlled mainly by climatic perturbations, a transition occurred to anthropogenically-controlled systems during the Middle to Late Holocene. When exactly this transition of fluvial systems took place and to what degree different anthropogenic practices played a role is not yet fully understood. It is an important hiatus to address in our understanding of riverine landscapes and the search for sustainable future scenarios in light of the changing climate.Floodplains constitute an ideal setting to address this issue, as their sediments record past river dynamics and human activities (e.g., settling, milling, mining, logging, agriculture). In contrast to the extensively studied Upper Rhine plain, it remains largely unclear how human alteration of fluvial systems climbed up the Rhine tributaries. Here, we use a combination of geophysical surveys, sedimentological investigations, luminescence dating, and heavy metal analysis at three sites to investigate how and when anthropogenic land use changes shifted the rhenian meso-scale Kinzig river from a natural to an anthropogenically-dominated fluvial system.Our sedimentological analyses reveal three distinct phases (Late Pleistocene/Early Holocene till 9.00 ka BP, Mid/Late Holocene 9.00-0.82 ka BP, modern 0.81-0 ka BP) of floodplain accumulation, characterized by increasing accumulation rates (ca. 0.09 mm/a, 0.33 mm/a, 1.07 mm/a) and decreasing grain sizes. Concomitantly with the increase of mining activity that peaked between the 16th and 18th centuries, and heavy metal concentrations in the floodplain rise (enrichment factors of Ba, Pb, and Cu peaking at ca. 2.5, 4.0, and 3.0), suggesting a close link between these sediment contaminations and historic land use and mining records from the catchment.Hence, cross-referencing the floodplain stratigraphy with catchment land use history allows for argumentation of a gradual shift from a somewhat natural to an anthropogenically altered system. It implies a time-conform response to later human settlement relative to the Upper Rhine plain and an intensification of anthropogenic impact in the floodplain stratigraphy over the last ca. 2500 years, in line with the unprecedented high floodplain accumulation rates relative to pre-human presence
Digital interventions in mental health: an overview and future perspectives
No full textAs e-health offerings rapidly expand, they are transforming and challenging traditional mental health care systems globally, presenting both promising opportunities and significant risks. This article critically examines the potential and pitfalls of integrating digital technologies into mental health care, particularly in the realms of diagnosis, prevention, and treatment. It explores current advancements and evidence-based practices, and provides a vision for how future technologies can evolve responsibly to meet mental health needs. The article concludes with the TEQUILA framework, addressing essential elements and challenges for fostering a beneficial and ethical future. A responsible future for digital mental health requires building Trust by ensuring data privacy, security, and transparency in AI-driven decisions, along with Evidence-based and robust regulatory oversight to maintain Quality. Usability, design, usability tailored to diverse needs, and ethical alignment with users' Interests will all be essential, while Liability and Accreditation standards will safeguard accountability in this evolving landscape
Computational modelling of biological systems now and then: revisiting tools and visions from the beginning of the century
No full textSince the turn of the millennium, computational modelling of biological systems has evolved remarkably and sees matured use spanning basic and clinical research. While the topic of the peri-millennial debate about the virtues and limitations of ‘reductionism and integrationism’ seems less controversial today, a new apparent dichotomy dominates discussions: mechanistic versus data-driven modelling. In light of this distinction, we provide an overview of recent achievements and new challenges with a focus on the cardiovascular system. Attention has shifted from generating a universal model of the human to either models of individual humans (digital twins) or entire cohorts of models representative of clinical populations to enable in silico clinical trials. Disease-specific parametrization, inter-individual and intra-individual variability, uncertainty quantification as well as interoperable, standardized and quality-controlled data are important issues today, which call for open tools, data and metadata standards, as well as strong community interactions. The quantitative, biophysical and highly controlled approach provided by in silico methods has become an integral part of physiological and medical research. In silico methods have the potential to accelerate future progress also in the fields of integrated multi-physics modelling, multi-scale models, virtual cohort studies and machine learning beyond what is feasible today. In fact, mechanistic and data-driven modelling can complement each other synergistically and fuel tomorrow’s artificial intelligence applications to further our understanding of physiology and disease mechanisms, to generate new hypotheses and assess their plausibility, and thus to contribute to the evolution of preventive, diagnostic and therapeutic approaches