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The aim of this cross-sectional study was to assess retinal oxygen metabolism in patients with type 2 diabetes and different stages of nonproliferative diabetic retinopathy (DR) (n = 67) compared with healthy control subjects (n = 20). Thirty-four patients had no DR, 15 had mild DR, and 18 had moderate to severe DR. Retinal oxygen saturation in arteries and veins was measured using the oxygen module of a retinal vessel analyzer. Total retinal blood flow (TRBF) was measured using a custom-built Doppler optical coherence tomography system. Retinal oxygen extraction was calculated from retinal oxygen saturation and TRBF. Arteriovenous difference in oxygen saturation was highest in healthy subjects (34.9 ± 7.5%), followed by patients with no DR (32.5 ± 6.3%) and moderate to severe DR (30.3 ± 6.5%). The lowest values were found in patients with mild DR (27.3 ± 8.0%, P = 0.010 vs. healthy subjects). TRBF tended to be higher in patients with no DR (40.1 ± 9.2 μL/min) and mild DR (41.8 ± 15.0 μL/min) than in healthy subjects (37.2 ± 5.7 μL/min) and patients with moderate to severe DR (34.6 ± 10.4 μL/min). Retinal oxygen extraction was the highest in healthy subjects (2.24 ± 0.57 μL O2/min), followed by patients with no DR (2.14 ± 0.6 μL O2/min), mild DR (1.90 ± 0.77 μL O2/min), and moderate to severe DR (1.78 ± 0.57 μL O2/min, P = 0.040 vs. healthy subjects). These results indicate that retinal oxygen metabolism is altered in patients with type 2 diabetes. Furthermore, retinal oxygen extraction decreases with increasing severity of DR.

Metabolomics is an emerging and powerful molecular profiling method supporting clinical investigations. For clinical metabolomics studies, serum is commonly used. Serum is collected after blood coagulation, a complex biochemical process involving active platelet metabolism. This may proof relevant as platelet counts and function may vary substantially in individuals. Applying a multi-omics analysis strategy comprising proteins and metabolites with a focus on lipid mediators, we systematically investigated serum and plasma obtained from the same healthy donors. While Biocrates MxP Quant 500 results correlated well (n=461, R2=0.991), lipid mediators (n=77, R2=0.906) and proteins (n=322, R2=0.860) differed substantially between serum and plasma. Actually, secretome analysis of activated platelets identified all proteins and most lipid mediators significantly enriched in serum when compared to plasma. Furthermore, a prospective, randomized, controlled parallel group metabolomics trial was performed, monitored by serum and plasma analyses. Healthy individuals received either acetylsalicylic acid, affecting platelets, or omega-3 fatty acids, hardly affecting platelets, for a period of seven days. In the acetylsalicylic acid group, serum analysis apparently demonstrated a significant drug-induced downregulation of the lipid mediators TXB2 and 12-HETE. The absence of these observation in plasma analyses suggested that these drug effects took place only during blood coagulation. Other effects of acetylsalicylic acid on alpha-linolenic acid and the fatty acid composition of triglycerides were detected both in serum and plasma. In the omega-3 fatty acid group, serum and plasma analysis results did not differ. These data strongly support the hypothesis that the serum metabolome is substantially confounded by platelets.Key pointsSerum metabolomics data are confounded by plateletsClinical evaluation of drug effects should be based on plasma metabolomics

Introduction: The aim of this study was to compare the structure-function relationship with microperimetry and Octopus perimetry in primary open-angle glaucoma (POAG) patients with central visual field (VF) defects. Methods: Forty eyes of 24 patients with POAG were enrolled. Circumpapillary retinal nerve fiber layer (cpRNFL) analysis measured by spectral-domain optical coherence tomography (SD-OCT) of the superotemporal, temporal, and inferotemporal optic-nerve head sectors were related to corresponding microperimetric and Octopus VF clusters using the G2 grid-pattern with dynamic strategy, respectively. The structure-function relationships of both devices were assessed via a segmented regression, as well as linear regression across overall SD-OCT cpRNFL values and outside normative (Results: Linear and segmented regression fits were similar with both devices. Across overall cpRNFL sectorial values, structure-function relations for the superotemporal, temporal, and inferotemporal sectors were R2 = 0.176 (p = R2 = 0.008 (p = 0.069), and R2 = 0.294 (p = R2 = 0.189 (p = R2 = 0.020 (p = 0.002), and R2 = 0.326 (p = R2 = 0.113 (p = R2 = 0.001 (p = 0.836), and R2 = 0.420 (p = R2 = 0.192 (p = R2 = 0.002, (p = 0.336), and R2 = 0.366 (p = Discussion/Conclusion: Structure-function analysis was similar for both devices. Fundus-tracking should be further evaluated in a longitudinal setting in patients affected by glaucoma.

This is a review of new developments in entropic gravity in light of the Relativistic Transactional Interpretation (RTI). A transactional approach to spacetime events can give rise in a natural way to entropic gravity (in the way originally proposed by Erik Verlinde) while also overcoming extant objections to that research program. The theory also naturally gives rise to a Cosmological Constant and to Modified Newtonian Dynamics (MOND) and thus provides a physical explanation for the phenomena historically attributed to "dark energy" and "dark matter"., Comment: Final accepted version, Journal of Physics Communications (2023)

ZusammenfassungDurch die stetige Weiterentwicklung und Verbesserung der Technik hat die optische Kohärenztomographie (OCT) in den letzten Jahren neue Möglichkeiten zur Beurteilung der Strukturen des vorderen Augenabschnittes eröffnet. Aufgrund der Darstellung kleinster Strukturen, wie beispielsweise des Tränenfilms, nimmt die OCT in der Diagnostik und Verlaufsbeurteilung des trockenen Auges eine immer wichtigere Rolle ein. Der vorliegende Beitrag gibt einen Überblick über die derzeitigen Einsatzmöglichkeiten der OCT beim trockenen Auge.

We show that the real existence of quantum-events, resulting from spontaneously broken unitary-evolution by quantum-transactions, can explain the dynamic metric of space-time, governed by Einstein’s equation, if light-clocks are being used to measure the rhythm of events. In the derivation of Einstein’s equation there naturally arises a term for a cosmological constant Λ.

Aims/HypothesisThere is evidence that diabetes is accompanied by a break-down of functional hyperemia, an intrinsic mechanism of neural tissues to adapt blood flow to changing metabolic demands. However, to what extent functional hyperemia is altered in different stages of diabetic retinopathy (DR) in patients with type II diabetes is largely unknown. The current study set out to investigate flicker-induced retinal blood flow changes in patients with type II diabetes at different stages of DR.Materials and methodsA total of 76 subjects were included in the present parallel-group study, of which 56 had diabetes with either no DR or different stages of non-proliferative DR (n = 29 no DR, 12 mild DR, 15 moderate to severe DR). In addition, 20 healthy subjects were included as controls. Retinal blood flow was assessed before and during visual stimulation using a combined measurement of retinal vessel calibers and blood velocity by the means of Doppler optical coherence tomography (OCT). To measure systemic autonomic nervous system function, heart rate variability (HRV) was assessed using a short-term orthostatic challenge test.ResultsIn healthy controls, retinal blood flow increased by 40.4 ± 27.2% during flicker stimulation. Flicker responses in patients with DR were significantly decreased depending on the stage of the disease (no DR 37.7 ± 26.0%, mild DR 26.2 ± 28.2%, moderate to severe DR 22.3 ± 13.9%; p = 0.035, ANOVA). When assessing systemic autonomous neural function using HRV, normalized low frequency (LF) spectral power showed a significantly different response to the orthostatic maneuver in diabetic patients compared to healthy controls (p < 0.001).Conclusion/InterpretationOur study indicates that flicker induced hyperemia is reduced in patients with DR compared to healthy subjects. Further, this impairment is more pronounced with increasing severity of DR. Further studies are needed to elucidate mechanisms behind the reduced hyperemic response in patients with type II diabetes.Clinical trial registration[https://clinicaltrials.gov/], identifier [NCT03 552562].

Background/aims Concerning healthcare approaches, a paradigm change from reactive medicine to predictive approaches, targeted prevention, and personalisation of medical services is highly desirable. This raises demand for biomarker signatures that support the prediction and diagnosis of diseases, as well as monitoring strategies regarding therapeutic efficacy and supporting individualised treatments. New methodological developments should preferably rely on non-invasively sampled biofluids like sweat and tears in order to provide optimal compliance, reduce costs, and ensure availability of the biomaterial. Here, we have thus investigated the metabolic composition of human tears in comparison to finger sweat in order to find biofluid-specific marker molecules derived from distinct secretory glands. The comprehensive investigation of numerous biofluids may lead to the identification of novel biomarker signatures. Moreover, tear fluid analysis may not only provide insight into eye pathologies but may also be relevant for the prediction and monitoring of disease progression and/ or treatment of systemic disorders such as type 2 diabetes mellitus. Methods Sweat and tear fluid were sampled from 20 healthy volunteers using filter paper and commercially available Schirmer strips, respectively. Finger sweat analysis has already been successfully established in our laboratory. In this study, we set up and evaluated methods for tear fluid extraction and analysis using high-resolution mass spectrometry hyphenated with liquid chromatography, using optimised gradients each for metabolites and eicosanoids. Sweat and tears were systematically compared using statistical analysis. As second approach, we performed a clinical pilot study with 8 diabetic patients and compared them to 19 healthy subjects. Results Tear fluid was found to be a rich source for metabolic phenotyping. Remarkably, several molecules previously identified by us in sweat were found significantly enriched in tear fluid, including creatine or taurine. Furthermore, other metabolites such as kahweol and various eicosanoids were exclusively detectable in tears, demonstrating the orthogonal power for biofluid analysis in order to gain information on individual health states. The clinical pilot study revealed that many endogenous metabolites that have previously been linked to type 2 diabetes such as carnitine, tyrosine, uric acid, and valine were indeed found significantly up-regulated in tears of diabetic patients. Nicotinic acid and taurine were elevated in the diabetic cohort as well and may represent new biomarkers for diabetes specifically identified in tear fluid. Additionally, systemic medications, like metformin, bisoprolol, and gabapentin, were readily detectable in tears of patients. Conclusions The high number of identified marker molecules found in tear fluid apparently supports disease development prediction, developing preventive approaches as well as tailoring individual patients’ treatments and monitoring treatment efficacy. Tear fluid analysis may also support pharmacokinetic studies and patient compliance control.

At the moment, cataract, which is the opacification of the eye’s lens, can only be treated by surgery. In order to develop and test new pharmacological treatment strategies for the disease, there is a need for an appropriate in vitro model using ex vivo animal lenses. In this study, porcine lenses were incubated in either culture medium, glucose, triamcinolone acetonide, sodium chloride, hydrogen peroxide, sodium selenite, neutral buffered formalin, or were exposed to microwave heating to experimentally induce lens opacification. Changes in the lens morphology, weight, size, and elasticity were monitored 7 days after treatment. The fastest induction of dense opacification was seen in lenses exposed to sodium chloride, neutral buffered formalin, and microwave heating. No change in the size and weight of the lenses were detected, whereas loss in elasticity could be detected in lenses treated with formalin solution or microwave heating. Thus, neutral buffered formalin- and microwave-treated ex vivo porcine lenses seem to be a suitable model for mature cataracts, whereas hypertonic sodium chloride may be useful for studies on osmolarity-induced lens opacification.

The true nature of space and time has been a topic of natural philosophy, passed down since the presocratic era. In modern times reflection has particularly been inspired by the physical theories of Newton and Einstein and, more recently, by the quest for a theory of quantum gravity. In this paper we want to specify the idea that material systems and their spatio-temporal distances emerge from quantum-events. We will show a mechanism, by which quantum-events induce a metric field between material systems, which is governed by Einstein's equation including a cosmological constant.

We compare the focal structure-function correlation of structural measurements of peripapillary retinal nerve fiber layer thickness (RNFL-T) using optical coherence tomography (OCT), capillary density (CD) measurements using OCT-angiography (OCT-A), or a combination of both, with visual field deviation (VFD) in early to advanced glaucoma. Primary open angle glaucoma patients (n = 46, mean ± SD age: 67 ± 10 years; VF mean deviation: -10.41 ± 6.76 dB) were included in this cross-sectional study. We performed 30-2 standard automated perimetry OCT (3.5-mm diameter ring scan) and 15°×15° OCT-A (superficial vascular complex slab). Based on a nerve fiber trajectory model, each VF test spot was assigned to an OCT-A wedge and an OCT ring-sector. Two univariate linear models (Mv and Mt ) using either CD-based vascular (Mv ) or RNFL-T-based thickness information (Mt ) and one multivariate model using both (Mv:t ) were compared in their associations with measured focal VFD, which were higher for the multivariate model Mv:t (mean ± SD correlation coefficient: 0.710 ± 0.086) than for either nested model (0.627 ± 0.078 for Mv and 0.578 ± 0.095 for Mt ). Using a focal visual field approach, the combination of RNFL-T and CD showed better structure-function correlations than thickness or vascular information only. Agency for Science, Technology and Research (A*STAR) Nanyang Technological University National Research Foundation (NRF) Published version Financial support from the Austrian Science Fund FWF Project KLI 854, the National Medical Research Council (CG/C010A/2017;OFIRG/0048/2017; OFLCG/004c/2018; and TA/MOH-000249-00/2018), the National Research Foundation Singapore, A∗STAR (A20H4b0141),the Singapore Eye Research Institute & Nanyang Technological University (SERI-NTU Advanced Ocular Engineering (STANCE) Program),the Duke-NUS Medical School (Duke-NUS-KP(Coll)/2018/0009A), and the SERI-Lee Foundation (LF1019-1) Singapore is gratefully acknowledged.

Purpose The aim of this retrospective analysis was to investigate whether trabeculectomy (TRAB) and XEN® Gel Stent implantation (XEN) - both filtrating surgery techniques - can slow down the deterioration of visual field (VF) parameters considering the floor effect, which could lead to a misestimation of pre- and postoperative VF rate of progression (ROP). Methods Included in this study were patients with open-angle glaucoma, who underwent either TRAB or XEN® gel stent implantation and who had at least three VF tests before and after surgery, over an observation period of 13 years. The annual ROP of the mean defect (MD) and the square root of loss variance (sLV) were calculated with two different censoring thresholds: by censored regression and by ordinary least squares regression (OLSR). In addition, the diagnostic range of sLV was calculated. Results 48 eyes of 39 glaucoma patients were included in the study. The annual rate of MD progression was significantly reduced by filtering surgery when calculating the yearly ROP using OLSR (p = 0.006) and by censoring values exceeding a precalculated cut-off of 14.20 dB (p = 0.041) and a cut-off from the literature of 15.00 dB (p = 0.028). On average, the MD was impacted by a significant floor effect of 14.20 dB (95% CI: 12.83-15.56), corresponding to 17.7/59 absolute defects or 29.9% of the whole VF. When applying both OLSR and censored regression, the annual rate of sLV progression did not show a significant difference. The sLV showed a diagnostic boundary at a MD of 15.78 dB. Conclusion This study shows that filtering surgery can reduce the progression of VF in patients with open-angle glaucoma, especially those whose disease develops aggressively. This is valid even if the floor effect in advanced cases is compensated by censored regression. On average, the ROP of MD is affected by a significant floor effect at about 29.9% absolute loss of the whole VF.

In neural tissues, the coupling between neural activity and blood flow is a physiological key principle in blood flow regulation. We used optical coherence tomography angiography to investigate stimulus-evoked hemodynamic responses in different microvascular layers of the human retina. Twenty-two healthy subjects were included. Vessel density before and during light stimulation was measured using optical coherence tomography angiography and assessed for the superficial, intermediate, and deep capillary plexus of the retinal circulation. Volumetric blood flow was measured using a custom-built Doppler optical coherence tomography system. Our results show that flicker stimulation induced a significant increase in the vessel density of +9.9 ± 6.7% in the superficial capillary plexus, +6.6 ± 1.7% in the intermediate capillary plexus, and +4.9 ± 2.3% in the deep capillary plexus. The hyperemic response of the superficial capillary plexus was significantly higher compared to the intermediate capillary plexus (

The Born-rule, which assigns probabilities to measurement outcomes, is one of the fundamental axioms of quantum physics. It dates back to the time of the establishment of the formalism of quantum physics in the first half of the 20th century. From the beginning, and particularly in connection with the development of different interpretations of the theory, there has been a desire/need to better understand the true nature of the Born-probabilities. Are they classical/epistemic of origin or are they irreducible and of on tic stature as a kind of intrinsic propensities of physical systems? We show that, by only using the mathematical formalism of the original theory, we find a possible answer.

The clock-hypothesis is the fundamental assumption in the theories of relativity that duration, measured by clocks, is proportionate to the length of their respective world lines. Over the years, there have been contributions both, theoretical and experimental in nature, either confirming or questioning this hypothesis. We give an elementary model of two classes of clocks, which turn out to be relativistic clocks, and by doing so also offer a basis to see the limitations of the clock-hypothesis. At the same time, we find support for a hypothesis of L. de Broglie, regarding the existence of an internal clock of electrons. Our aim is to give a precise, yet accessible account of the subject.

We use an information-consistency or, equivalently, a thermodynamic equilibrium condition to derive Einstein’s equations, both in case of a gravitational and an electrostatic field. We thus show the equivalence of an information-theoretic and a thermodynamic viewpoint in the analysis of the geometry of space-time.

The southern end of the Upper Rhine Graben is one of the zones in Switzerland where recent crustal movements can be expected because of ongoing seismotectonic processes as witnessed by seismicity clusters occurring in this region. Therefore, in 1973 a control network with levelling profiles across the eastern Rhine Graben fault was installed and measured in the vicinity of the city of Basel in order to measure relative vertical movements and investigate their relationship with seismic events. As a contribution to EUCOR-URGENT, the profiles were observed a third time in the years 2002 and 2003 and connected to the Swiss national levelling network. The results of these local measurements are discussed in terms of accuracy and significance. Furthermore, they are combined and interpreted together with the extensive data set of recent vertical movements in Switzerland (Jura Mountains, Central Plateau and the Alps). In order to be able to prove height changes with precise levelling, their values should amount to at least 3–4 mm (1σ). The present investigations, however, have not shown any significant vertical movements over the past 30 years.

The official height system of Switzerland LNO2 is based on levelling measurements only, without taking into account the gravity field. This causes inconsistencies for the surveyors who nowadays often determine heights out of GPS measurements and geoid information.

Im Gegensatz zum betrieblichen Finanz- und Rechnungswesen, welches auf eine Tradition von uber 400 Jahren zuruckblicken kann und trotz shcon recht ausgereiften Methoden such heute noch kontinuierlich weiterentwickelt wird, ist die Diskussion um Umweltdaten eine noch reativ junge Disziplin. Mit dem konzept der okologischen Buchhaltung,welches sich an die finanzielle Buchhaltung anlehnt, wurde von Muller-Wenk25 1978 ein in sich geschlossenes Konzept der Umweltdatenbereitstellung prasentiert.26 Neue Erkenntnisse, Methoden, Normen oder Techniken verandern jedoch laufend die Landschaft der Wahrnehmung der Umweltproblematik und somit auch die Bedurfnisse der Datenakqyisition. Weiter-entwicklung der Bereitstellung von Umweltdaten als Basis okologieorientierter Lernprozesse in Unternehmen.

Der Umwelt-Dialog auf institutionalisierten Plattformen fur die gemeinsame Diskussion der Informationsbedurfnisse und den Handlungsbedarf, ist einer der entscheidenden Faktoren fur den Aufbau okologieorientierter Lernprozesse in Unternehmen. Der Umwelt-Dialog ist sowohl nach innen, wie aber auch nach aussen gerichtet. Fur ein erfolgreiches Umweltmanagement und Umweltinformationsmanagement sind sowohl die internen als auch die externen Anspruchsgruppen mit ihren Informationsbedurfnissen in diesen Umwelt-Dialog miteinzubeziehen. Der nach innen gerichtete Umwelt-Dialog dient dem Aufbau eines gemeinsamen Verstandnisses uber das Unternehmen selbst, uber die Umweltproblematik wie auch uber den Handlungsbedarf zur kontinuierlichen Vermeidung und Verminderung der Umwelteinwirkungen der Tatigkeiten, Produkte und Dienstleistungen. Der Umwelt-Dialog mit den externen Anspruchsgruppen ermoglicht den beidseitigen Aufbau des Verstandnisses uber die Informationsbedurfnisse und die Moglichkeiten zur Bereitstellung der entsprechenden Daten. Durch das Verstehenlernen der beabsichtigten Aussagen der Anspruchsgruppen kann mit dem Aufbau eines partnerschaftlichen Umwelt-Dialogs auch das Misstrauen und die Angst davor ausgeraumt werden, die Anspruchsgruppen wurden die erhaltenen Daten zuungunsten des Unternehmens verwenden.

Die bisherigen Ausfuhrungen haben gezeigt, dass die Anstrengungen im betrieblichen Umweltschutz teilweise nur wenig Erfolg gezeigt haben. Ebenso wurden Defizite herausgearbeitet, die klar darauf hinweisen, dass Veranderungen im Umweltdenken notwendig sind. Die Unternehmen mussen die verursachten Umwelteinwirkungen feststellen, vermindern und wenn moglich vermeiden. Dazu ist einerseits eine faktenorientierte Entscheidungsgrundlage notwendig. Andererseits ist das Wissen und das Verstandnis fur die Nutzung dieser Entscheidungsgrundlagen im Unternehmen aufzubauen.

Nach den Untersuchungen zur Bereitstellung von Umweltdaten und zu den systemischen Voraussetzungen, welche fur das okologieorientierte Handeln geschaffen werden mussen, soll nachfolgend untersucht werden, wie eine Systematik der Umweltdatenbereitstellung konkret aufgebaut werden kann. In einem ersten Teil wird basierend auf den bisher erarbeiteten Erkenntnissen ein Umweltinformationssystem im Sinne einer konsistenten Systematik konzipiert. Aufbauend auf einem bestehenden Referenzmodell wird gezeigt, wie ausgehend von der Datenverwendung in einer gemeinsamen Erkundung der betrieblichen Realitat schrittweise der Datenbedarf abgeleitet werden kann. Dazu werden die Anspruchsgruppen, deren Informationsbedurfnisse sowie die beabsichtigten Handlungen untersucht. Aufgrund dieser Bedurfnisse wird anschliessend die Systematik zur Informationsbedarfsanalyse und zur benutzerorientierten Datenaufbereitung und -kommunikation abgeleitet. Diese Systematik findet mit den Anforderungen an ein Vorgehen zur Umsetzung in die Praxis ihren Abschluss.