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Background Signal complexity (i.e. entropy) describes the level of order within a system. Low physiological signal complexity predicts unfavorable outcome in a variety of diseases and is assumed to reflect increased rigidity of the cardio/cerebrovascular system leading to (or reflecting) autoregulation failure. Aneurysmal subarachnoid hemorrhage (aSAH) is followed by a cascade of complex systemic and cerebral sequelae. In aSAH, the value of entropy has not been established yet. Methods aSAH patients from 2 prospective cohorts (Zurich—derivation cohort, Aachen—validation cohort) were included. Multiscale Entropy (MSE) was estimated for arterial blood pressure, intracranial pressure, heart rate, and their derivatives, and compared to dichotomized (1–4 vs. 5–8) or ordinal outcome (GOSE—extended Glasgow Outcome Scale) at 12 months using uni- and multivariable (adjusted for age, World Federation of Neurological Surgeons grade, modified Fisher (mFisher) grade, delayed cerebral infarction), and ordinal methods (proportional odds logistic regression/sliding dichotomy). The multivariable logistic regression models were validated internally using bootstrapping and externally by assessing the calibration and discrimination. Results A total of 330 (derivation: 241, validation: 89) aSAH patients were analyzed. Decreasing MSE was associated with a higher likelihood of unfavorable outcome independent of covariates and analysis method. The multivariable adjusted logistic regression models were well calibrated and only showed a slight decrease in discrimination when assessed in the validation cohort. The ordinal analysis revealed its effect to be linear. MSE remained valid when adjusting the outcome definition against the initial severity. Conclusions MSE metrics and thereby complexity of physiological signals are independent, internally and externally valid predictors of 12-month outcome. Incorporating high-frequency physiological data as part of clinical outcome prediction may ena

Spectrum power analysis in the low frequency oscillations (LFO) region of functional near infrared spectroscopy (fNIRS) is a promising method to deliver information about brain activation and therefore might be used for prognostication in patients with disorders of consciousness in the neurocritical care unit alongside with established methods. In this study, we measure the cortical hemodynamic response measured by fNIRS in the LFO region following auditory and somatosensory stimulation in healthy subjects. The significant hemodynamic reaction in the contralateral hemisphere correlation with the physiologic electric response suggests neurovascular coupling. In addition, we investigate power spectrum changes in steady state measurements of cerebral death patients and healthy subjects in the LFO region, the frequency of the heartbeat and respiration. The spectral power within the LFO region was lower in the patients with cerebral death compared to the healthy subjects, whereas there were no differences in spectral power for physiological activities such as heartbeat and respiration rate. This finding indicates the cerebral origin of our low frequency measurements. Therefore, LFO measurements are a potential method to detect brain activation in patients with disorders of consciousness and cerebral death. However, further studies in patients are needed to investigate its potential clinical use.

Delayed cerebral ischemia (DCI) occurs in up to one third of patients suffering from aneurysmal subarachnoid hemorrhage (aSAH). Untreated, it leads to secondary cerebral infarctions and is frequently associated with death or severe disability. After aneurysm rupture, erythrocytes in the subarachnoid space lyse and liberate free hemoglobin (Hb), a key driver for the development of DCI. Hemoglobin in the cerebrospinal fluid (CSF-Hb) can be analyzed through a two-step procedure of centrifugation to exclude intact erythrocytes and subsequent spectrophotometric quantification. This analysis can only be done in specialized laboratories but not at the bedside in the intensive care unit. This limits the number of tests done, increases the variability of the results and restricts accuracy. Bedside measurements of CSF-Hb as a biomarker with a point of care diagnostic test system would allow for a continuous monitoring for the risk of DCI in the individual patient. In this study, a microfluidic chip was explored that allows to continuously separate blood particles from CSF or plasma based on acoustophoresis. An in vitro test bench was developed to test in-line measurements with the developed microfluidic chip and a spectrometer. The proof of principle for a continuous particle separation device has been established with diluted blood and CSF samples from animals and aSAH patients, respectively. Processing 1 mL of blood in our microfluidic device was achieved within around 70 min demonstrating only minor deviations from the gold standard centrifugation (7% average error of patient samples), while saving several hours of processing time and additionally the reduction of deviations in the results due to manual labor.

We describe the design and results from the BraTS 2023 Intracranial Meningioma Segmentation Challenge. The BraTS Meningioma Challenge differed from prior BraTS Glioma challenges in that it focused on meningiomas, which are typically benign extra-axial tumors with diverse radiologic and anatomical presentation and a propensity for multiplicity. Nine participating teams each developed deep-learning automated segmentation models using image data from the largest multi-institutional systematically expert annotated multilabel multi-sequence meningioma MRI dataset to date, which included 1000 training set cases, 141 validation set cases, and 283 hidden test set cases. Each case included T2, T2/FLAIR, T1, and T1Gd brain MRI sequences with associated tumor compartment labels delineating enhancing tumor, non-enhancing tumor, and surrounding non-enhancing T2/FLAIR hyperintensity. Participant automated segmentation models were evaluated and ranked based on a scoring system evaluating lesion-wise metrics including dice similarity coefficient (DSC) and 95% Hausdorff Distance. The top ranked team had a lesion-wise median dice similarity coefficient (DSC) of 0.976, 0.976, and 0.964 for enhancing tumor, tumor core, and whole tumor, respectively and a corresponding average DSC of 0.899, 0.904, and 0.871, respectively. These results serve as state-of-the-art benchmarks for future pre-operative meningioma automated segmentation algorithms. Additionally, we found that 1286 of 1424 cases (90.3%) had at least 1 compartment voxel abutting the edge of the skull-stripped image edge, which requires further investigation into optimal pre-processing face anonymization steps., Comment: 16 pages, 11 tables, 10 figures, MICCAI

Nonlinear waveguides with two distinct domains of anomalous dispersion can support the formation of molecule-like two-color pulse compounds. They consist of two tightly bound subpulses with frequency loci separated by a vast frequency gap. Perturbing such a two-color pulse compound triggers periodic amplitude and width variations, reminiscent of molecular vibrations. With increasing strength of perturbation, the dynamics of the pulse compound changes from harmonic to nonlinear oscillations. The periodic amplitude variations enable coupling of the pulse compound to dispersive waves, resulting in the resonant emission of multi-frequency radiation. We demonstrate that the location of the resonances can be precisely predicted by phase-matching conditions. If the pulse compound consists of a pair of identical subpulses, inherent symmetries lead to degeneracies in the resonance spectrum. Weak perturbations lift existing degeneracies and cause a splitting of the resonance lines into multiple lines. Strong perturbations result in more complex emission spectra, characterized by well separated spectral bands caused by resonant Cherenkov radiation and additional four-wave mixing processes.

We numerically explore synthetic crystal diamond for realizing novel light sources in ranges which are up to now difficult to achieve with other materials, such as sub-10-fs pulse durations and challenging spectral ranges. We assess the performance of on-chip diamond waveguides for controlling light generation by means of nonlinear soliton dynamics. The considered silica-embedded diamond waveguide model exhibits two zero-dispersion points, delimiting an anomalous dispersion range that exceeds an octave. Various propagation dynamics, including supercontinuum generation by soliton fission, can be realized in diamond photonics. In contrast to usual silica-based optical fibers, where such processes occur on the scale of meters, in diamond millimeter-scale propagation distances are sufficient. Unperturbed soliton-dynamics prior to soliton fission allow identifying a pulse self-compression scenario that promises record-breaking compression factors on chip-size propagation lengths.

We present a detailed overview of the physics of two-color soliton molecules in nonlinear waveguides, i.e. bound states of localized optical pulses which are held together due to an incoherent interaction mechanism. The mutual confinement, or trapping, of the subpulses, which leads to a stable propagation of the pulse compound, is enabled by the nonlinear Kerr effect. Special attention is paid to the description of the binding mechanism in terms of attractive potential wells, induced by the refractive index changes of the subpulses, exerted on one another through cross-phase modulation. Specifically, we discuss nonlinear-photonics meta atoms, given by pulse compounds consisting of a strong trapping pulse and a weak trapped pulse, for which trapped states of low intensity are determined by a Schrödinger-type eigenproblem. We discuss the rich dynamical behavior of such meta-atoms, demonstrating that an increase of the group-velocity mismatch of both subpulses leads to an ionization-like trapping-to-escape transition. We further demonstrate that if both constituent pulses are of similar amplitude, molecule-like bound-states are formed. We show that -periodic amplitude variations permit a coupling of these pulse compound to dispersive waves, resulting in the resonant emission of Kushi-comb-like multi-frequency radiation.

We report for the first time a metal-free heterogeneously catalyzed hydrogenation using a semi-solid frustrated Lewis pair (FLP). The catalyst consists of a solid polyamine organic framework and molecular tris(pentafluorophenyl)borane (BCF) that form a semi-immobilized FLP in situ in the catalytic hydrogenation of diethyl benzylidenemalonate. 11B NMR spectroscopy proves the successful hydrogen activation by the FLP. Furthermore, the B−N interactions between the polyamine and BCF are investigated by IR and solid state NMR spectroscopy. The FLP 1,4-diazabicyclo[2.2.2]octane (DABCO)/BCF, which combines the features of a FLP and a classical Lewis adduct, functions as molecular reference in both, catalysis and characterization. Furthermore, computational studies enable a better insight into the hydrogen activation through DABCO/BCF and polyamine/BCF.

Epimerization of sugars is a carbon-efficient route not only to produce rare carbohydrates but also to extend the product scope for chemical production in future biorefineries. Industrially available catalysts for epimerization are limited mainly to soluble Mo(VI) species as well as substrate-specific epimerases. Here we report highly active and selective tin-organic frameworks (Sn-OF) as solid catalysts for the epimerization of aldoses at the C-2 position, such as the conversion of glucose to mannose. The reaction proceeds via a carbon skeleton rearrangement, that is, through breaking of a C-2/C-3 carbon bond and formation of a C-1/C-3 bond. Partially hydrolyzed Ph₃Sn-OH sites were found to be the catalytically active centers. Our results suggest that the high catalytic activity of Sn-OFs for the epimerization is determined by (1) Lewis acidity of tin; (2) free Sn-OH groups; and (3) the high hydrophobicity of organic linkers applied in the aqueous solutions.

Do people feel better about themselves on days when they are more satisfied with their relationship? This study addressed this question in a sample of 238 first-time parents who provided daily reports of their self-esteem and relationship quality 6 weeks before, 6 months after, and 18 months after the birth of their first child. Consistent with theory and between-person evidence, we found both mothers and fathers to have higher self-esteem on days when they were more satisfied with their relationship than on an average day. The link between daily relationship quality and self-esteem was robust across the transition to parenthood and generalized across people with different levels of dispositional self-esteem and ages.

Explainable artificial intelligence (XAI) has emerged as a promising solution for addressing the implementation challenges of AI/ML in healthcare. However, little is known about how developers and clinicians interpret XAI and what conflicting goals and requirements they may have. This paper presents the findings of a longitudinal multi-method study involving 112 developers and clinicians co-designing an XAI solution for a clinical decision support system. Our study identifies three key differences between developer and clinician mental models of XAI, including opposing goals (model interpretability vs. clinical plausibility), different sources of truth (data vs. patient), and the role of exploring new vs. exploiting old knowledge. Based on our findings, we propose design solutions that can help address the XAI conundrum in healthcare, including the use of causal inference models, personalized explanations, and ambidexterity between exploration and exploitation mindsets. Our study highlights the importance of considering the perspectives of both developers and clinicians in the design of XAI systems and provides practical recommendations for improving the effectiveness and usability of XAI in healthcare.

BACKGROUND: Data on critically ill patients with spontaneous empyema or brain abscess are limited. The aim was to evaluate clinical presentations, factors, and microbiological findings associated with the outcome in patients treated in a Neurocritical Care Unit. METHODS: In this retrospective study, we analyzed 45 out of 101 screened patients with spontaneous epidural or subdural empyema and/or brain abscess treated at a tertiary care center between January 2012 and December 2019. Patients with postoperative infections or spinal abscess were excluded. Medical records were reviewed for baseline characteristics, origin of infection, laboratory and microbiology findings, and treatment characteristics. The outcome was determined using the Glasgow outcome scale extended (GOSE). RESULTS: Favorable outcome (GOSE 5-8) was achieved in 38 of 45 patients (84%). Four patients died (9%), three remained severely disabled (7%). Unfavorable outcome was associated with a decreased level of consciousness at admission (Glasgow coma scale < 9) (43% versus 3%; p = 0.009), need of vasopressors (71% versus 11%; p = 0.002), sepsis (43% versus 8%; p = 0.013), higher age (65.1 ± 15.7 versus 46.9 ± 17.5 years; p = 0.014), shorter time between symptoms onset and ICU admission (5 ± 2.4 days versus 11.6 ± 16.8 days; p = 0.013), and higher median C-reactive protein (CRP) serum levels (206 mg/l, range 15-259 mg/l versus 17.5 mg/l, range 3.3-72.7 mg/l; p = 0.036). With antibiotics adapted according to culture sensitivities in the first 2 weeks, neuroimaging revealed a progression of empyema or abscess in 45% of the cases. CONCLUSION: Favorable outcome can be achieved in a considerable proportion of an intensive care population with spontaneous empyema or brain abscess. Sepsis and more frequent need for vasopressors, associated with unfavorable outcome, indicate a fulminant course of a not only cerebral but systemic infection. Change of antibiotic therapy according to microbiological findings in the

The High Energy X-ray Probe is a proposed NASA probe-class mission that combines the power of high angular resolution with a broad X-ray bandpass to provide the necessary leap in capabilities to address the important astrophysical questions of the next decade. HEX-P achieves breakthrough performance by combining technologies developed by experienced international partners. HEX-P will be launched into L1 to enable high observing efficiency. To meet the science goals, the payload consists of a suite of co-aligned X-ray telescopes designed to cover the 0.2 - 80 keV bandpass. The High Energy Telescope (HET) has an effective bandpass of 2 - 80 keV, and the Low Energy Telescope (LET) has an effective bandpass of 0.2 - 20 keV. The combination of bandpass and high observing efficiency delivers a powerful platform for broad science to serve a wide community. The baseline mission is five years, with 30% of the observing time dedicated to the PI-led program and 70% to a General Observer (GO) program. The GO program will be executed along with the PI-led program., Comment: 10 pages, 8 figures, to be submitted to Frontiers

Purpose Definitive fascial closure is an essential treatment objective after open abdomen treatment and mitigates morbidity and mortality. There is a paucity of evidence on factors that promote or prevent definitive fascial closure. Methods A multi-center multivariable analysis of data from the Open Abdomen Route of the European Hernia Society included all cases between 1 May 2015 and 31 December 2019. Different treatment elements, i.e. the use of a visceral protective layer, negative-pressure wound therapy and dynamic closure techniques, as well as patient characteristics were included in the multivariable analysis. The study was registered in the International Clinical Trials Registry Platform via the German Registry for Clinical Trials (DRK00021719). Results Data were included from 630 patients from eleven surgical departments in six European countries. Indications for OAT were peritonitis (46%), abdominal compartment syndrome (20.5%), burst abdomen (11.3%), abdominal trauma (9%), and other conditions (13.2%). The overall definitive fascial closure rate was 57.5% in the intention-to-treat analysis and 71% in the per-protocol analysis. The multivariable analysis showed a positive correlation of negative-pressure wound therapy (odds ratio: 2.496, p < 0.001) and dynamic closure techniques (odds ratio: 2.687, p < 0.001) with fascial closure and a negative correlation of intra-abdominal contamination (odds ratio: 0.630, p = 0.029) and the number of surgical procedures before OAT (odds ratio: 0.740, p = 0.005) with DFC. Conclusion The clinical course and prognosis of open abdomen treatment can significantly be improved by the use of treatment elements such as negative-pressure wound therapy and dynamic closure techniques, which are associated with definitive fascial closure.

Selbstreflexivität eröffnet die Möglichkeit, eigene Irritationen, Gefühle und Assoziationen als Zugang zur Erkenntnis in den Forschungsprozess einzubeziehen. Einer Irritation nachzugehen, verlangt nach methodischen Wegen und reflexiven Verfahren der (Daten-)Triangulation und Interpretation. In diesem Beitrag veranschauliche ich anhand eines "irritierenden" Interviews, wie mir die Kombination von narrativer Positionierungsanalyse und ethnopsychoanalytischer Vorgehensweise dabei geholfen hat, meine Irritation besser zu verstehen und infolgedessen auch meine Emotion der Deutung zugänglich zu machen. Auf diesem Weg analysiere ich nicht nur die religiösen, sozialen und moralischen Positionierungspraktiken der interviewten Akteurin, sondern kann zeigen, wie innerhalb der Interviewbeziehung Inhalte und Formen kultureller und gesellschaftlicher Machtkonstellationen verhandelt wurden. Zuletzt reflektiere ich meine eigenen Vorannahmen und Anliegen, wodurch ich das theoretisch-praktische Verständnis der "selbstreflexiven Gesellschaftskritik" (EGGMANN 2009, S.255) neu ausloten und erweitern kann., Self-reflexivity is essential for ethnographic researchers and creates space to express their irritations, emotions, and associations which themselves can, in turn, lead to new insights. When irritation is felt, this needs to be considered using specific methods and reflexive techniques of data triangulation and methodological deliberation. In this article, I explain how the combination of narrative positioning analysis and ethnopsychological procedures helped me to understand my irritation while interviewing and how my emotions revealed themselves to be accessible to interpretation. Using a self-reflexive narration analysis approach, I identified the interviewee's religious, social, and moral positioning as well as how cultural and societal constellations are themselves bargained during the interview. I conclude by reflecting on my own suppositions, emotions, and concerns, which thus encourages me to broaden my theoretical and practical understanding of "self-reflexive social criticism" (EGGMANN, 2009, p.255).

Die Autroin beschäftigt sich im Anschluss an Paul Ricoeur mit der alltäglichen "schöpferischen Sinninterpretation" religiöser Akteur*innen im Zuge der Aktualisierung ihrer kanonischen Texte. Ihre Befragten äußern sich kritisch zu aktuellen ökonomischen Problematiken und generell zum Kapitalismus als Wirtschafts- und Gesellschaftssystem. Anhand der exemplarischen Differenz der muslimischen und christlichen Übersetzungsanstrengung stellt sie erste Hypothesen zu den Wechselwirkungen von strukturellen Divergenzen und Auslegungspraktiken auf., Referring to Paul Ricoeur the article examines the everyday "creative interpretation of sense" by religious actors. The interviewed persons manifested themselves as critical towards current economic problems and the capitalism as whole. Due to the differences regarding the muslim and christian translating effords the author establishes first hypotheses respective the consequences of structural divergency on interpreting practices.

The in-plant recycling routes of side streams produced in electric arc furnace (EAF) steelmaking remain underexplored. Briquetting is an attractive technique to enable their recycle. Briquettes introduced into EAF must possess certain mechanical and chemical properties. However, no standard is available to determine the suitability of briquettes used in the EAF process. Herein, eight side streams are characterized, and used to produce seven different briquettes to be used in EAF. Briquettes tested consist of four self-reducing briquettes and three slag-forming briquettes produced using different recipes. The briquettes are subjected to several mechanical and thermal tests which reflect their intended use in EAF. The mechanical tests include compression and drop tests, and the thermal tests include optical dilatometry, thermogravimetric analysis (TGA)–derivative thermogravimetry (DTG)–mass spectrometry (MS), and full-scale briquette reduction tests. Moreover, melting trials are performed to assess the melting behavior of selected briquettes and their interaction with slag. Suitability of briquettes characteristics is assessed based on values from the literature and against reference ferroalloys and lime stones used in one of the steel plants. Two briquettes are deemed suitable for EAF use, while three briquettes are deemed unsuitable, and two briquettes are considered of limited use.

The steel industry is on its way towards more environmentally friendly steelmaking. To achieve the ambitious goals of significant CO₂ emissions reduction, new processes, practices, sources of on-line data, and digitalization together with automation will be required. To address these issues, this paper discusses optical emission spectroscopy (OES) as an on-line data acquisition method for industrial electric arc furnaces and ladle furnaces. The current state of the OES as a measurement method in the steel industry together with prospects of new applications are presented with examples based on the authors’ prior research.

A column model of the Arctic atmosphere is developed including the nonlinear positive feedback responses of surface albedo and water vapour to temperature. The atmosphere is treated as a grey gas and the flux of longwave radiation is governed by the two-stream Schwarzschild equations. Water vapour concentration is determined by the Clausius-Clapeyron equation. Representative concentration pathways (RCPs) are used to model carbon dioxide concentrations into the future. The resulting 9D two-point boundary value problem is solved under various RCPs and the solutions analysed. The model predicts that under the highest carbon pathway, the Arctic climate will undergo an irreversible bifurcation to a warm steady state, which would correspond to annually ice-free conditions. Under the lowest carbon pathway, corresponding to very aggressive carbon emission reductions, the model exhibits only a mild increase in Arctic temperatures. Under the two intermediate carbon pathways, temperatures increase more substantially, and the system enters a region of bistability where external perturbations could possibly cause an irreversible switch to a warm, ice-free state.

BACKGROUND: Intracranial pressure (ICP) and arterial blood pressure (ABP) are related to each other through cerebral autoregulation. Central venous pressure (CVP) is often measured to estimate cardiac filling pressures as an approximate measure for the volume status of a patient. Prior modelling efforts have formalized the functional relationship between CVP, ICP and ABP. However, these models were used to explain short segments of data during controlled experiments and have not yet been used to explain the slowly evolving ICP increase that occurs typically in patients after aneurysmal subarachnoid hemorrhage (SAH). OBJECTIVE: To analyze the functional relationship between ICP, ABP and CVP recorded from SAH patients in the first five days after aneurysm. METHODS: Two methods were used to elucidate this relationship on the running average of the signals: First, using Spearman correlation coefficients calculated over 30 min segments Second, for each patient, linear state space models of ICP as the output and ABP and CVP as inputs were estimated. RESULTS: The mean and variance of the data and the correlation coefficients between ICP-ABP and ICP-CVP vary over time as the patient progresses through their stay in the ICU. On average, after an SAH event, the models show that a) ABP is the bigger driver of changes in ICP than CVP and that increasing ABP leads to reduction in ICP and (b) increasing CVP leads to an increase in ICP. CONCLUSIONS: Finding a) agrees with the hypothesis that patients with subarachnoid hemorrhage have defective autoregulation, and b) agrees with the positive correlation observed between central venous pressure and intracranial pressure in the literature.

Explainable AI (XAI) is considered the number one solution for overcoming implementation hurdles of AI/ML in clinical practice. However, it is still unclear how clinicians and developers interpret XAI (differently) and whether building such systems is achievable or even desirable. This longitudinal multi-method study queries (n=112) clinicians and developers as they co-developed the DCIP – an ML-based prediction system for Delayed Cerebral Ischemia. The resulting framework reveals that ambidexterity between exploration and exploitation can help bridge opposing goals and requirements to improve the design and implementation of AI/ML in healthcare.

Background: Rapid diagnosis of SARS-CoV-2 infection in patients not primarily assigned with the diagnosis of COVID-19 is highly relevant to effectively rule out virus transmission among patients and medical staff. The purpose is to develop a model for the prediction of the actual presence of a SARS-CoV-2 infection before a valid test result is available and to avoid unnecessary testing in Critical Care Units. Methods: Datasets of laboratory and blood gas analysis tests were collected retrospectively for the development and subsequent validation of machine learning (ML) based models. The data set was composed of 1. 254 SARS-CoV-2 positive cases, collected in an ICU dedicated to patients with COVID-19 pneumonia, 2a. 914 SARS-CoV-2 negative patients treated in a Neurocritical Care Unit and 2b. 32 patients treated for severe influenza pneumonia in a Medical ICU at the same hospital. The models were subsequently validated on a dataset collected from the Neurocritical Care Unit that consisted of data from 7 positive and 42 negative patients. Models were adapted to newly available laboratory values throughout their ICU stay. Extremely Randomized Trees (ERT) and Random Forest (RF) models were evaluated. A baseline model comprising fully grown trees, an optimized model including optimal values for the maximum depth, and a simplified model that only uses the 6 most important features were trained. Results: The overall best model, evaluated via crossvalidation on the development set, is an optimized ERT model with a ROC AUC value of 0.946. The model performance on the validation set is best for the simplified RF model achieving a ROC AUC value of 0.701. Gini feature and permutation importance for the simplified RF model revealed hemoglobin, procalcitonin, C-reactive protein, glomerular filtration rate based on CKD-EPI equation, creatinine, and urea as the most important input features. Using the simplified RF model and a threshold of 0.012 for the probability, a sensitivity ab

BackgroundFlow diversion treatment of ruptured cerebral aneurysms remains challenging due to the need for double-antiplatelet therapy. We report our experience with flow-diverter stent (FDS) reconstruction with single-antiplatelet therapy of ruptured cerebral blood blister and dissecting aneurysms.MethodsIn this case series we performed a retrospective analysis of all patients with ruptured cerebral aneurysms who were treated with a phosphoryl-bonded FDS between 2019 and 2022 in a single center. Periprocedurally, all patients received weight-adapted eptifibatide IV and heparin IV. After 6–24 hours, eptifibatide was switched to oral prasugrel as monotherapy. We analyzed the rate of bleeding complications, thromboembolic events, occlusion rate and clinical outcome.ResultsNine patients with subarachnoid hemorrhage were treated, eight within 24 hours of symptom onset. Seven patients were treated with one FDS and two patients received two FDS in a telescopic fashion. Two aneurysms were additionally coil embolized. Fatal re-rupture occurred in one case; eight patients survived and had no adverse events associated with the FDS. Six patients showed complete occlusion of the aneurysm after 3 months (n=2) and 1 year (n=4), respectively. Two patients showed subtotal occlusion of the aneurysm at the last follow-up after 3 months and 6 months, respectively. Favorable clinical outcome was achieved in five patients.ConclusionsPeri-interventional single-antiplatelet therapy with eptifibatide followed by prasugrel was sufficient to prevent thromboembolic events and reduce re-bleeding using an anti-thrombogenic FDS. FDS with single-antiplatelet therapy might be a viable option for ruptured blood blister and dissecting cerebral aneurysms.

Objective This pilot study assesses the feasibility to detect covert consciousness in clinically unresponsive patients by means of functional near infrared spectroscopy (fNIRS) in a real intensive care unit setting. We aimed to verify if the hemodynamic response to familiar music measured with fNIRS varies according to the level consciousness of the patients. Methods 22 neurocritical patients and 6 healthy controls were included. The experiment consisted in 3 subsequent blocks including a first resting state recording, a period of music playback and a second resting state recording. fNIRS measurement were performed on each subject with two optodes on the forehead. Main oscillatory frequencies of oxyhemoglobin signal were analyzed. Spectral changes of low frequency oscillations (LFO) between subsequent experimental blocks were used as a marker of cortical response. Cortical response was compared to the level of consciousness of the patients and their functional outcome, through validated clinical scores. Results Cortical hemodynamic response to music on the left prefrontal brain was associated with the level of consciousness of the patients and with their clinical outcome after three months. Conclusions Variations in LFO spectral power measured with fNIRS may be a new marker of cortical responsiveness to detect covert consciousness in neurocritical patients. Left prefrontal cortex may play an important role in the perception of familiar music. Significance We showed the feasibility of a simple fNIRS approach to detect cortical response in the real setting of an intensive care unit.

Background: Blood pressure variability (BPV) is associated with outcome after endovascular thrombectomy in acute large vessel occlusion stroke. We aimed to provide the optimal sampling frequency and BPV index for outcome prediction by using high-resolution blood pressure (BP) data. Methods: Patient characteristics, 3-month outcome, and BP values measured intraarterially at 1 Hz for up to 24 h were extracted from 34 patients treated at a tertiary care center neurocritical care unit. Outcome was dichotomized (modified Rankin Scale 0-2, favorable, and 3-6, unfavorable) and associated with systolic BPV (as calculated by using standard deviation, coefficient of variation, averaged real variability, successive variation, number of trend changes, and a spectral approach using the power of specific BP frequencies). BP values were downsampled by either averaging or omitting all BP values within each prespecified time bin to compare the different sampling rates. Results: Out of 34 patients (age 72 ± 12.7 years, 67.6% men), 10 (29.4%) achieved a favorable functional outcome and 24 (70.6%) had an unfavorable functional outcome at 3 months. No group differences were found in mean absolute systolic BP (SBP) (130 ± 18 mm Hg, p = 0.82) and diastolic BP (DBP) (59 ± 10 mm Hg, p = 1.00) during the monitoring time. BPV only reached predictive significance when using successive variation extracted from downsampled (averaged over 5 min) SBP data (median 4.8 mm Hg [range 3.8-7.1]) in patients with favorable versus 7.1 mmHg [range 5.5-9.7] in those with unfavorable outcome, area under the curve = 0.74 [confidence interval (CI) 0.57-0.85; p = 0.031], or the power of midrange frequencies between 1/20 and 1/5 min [area under the curve = 0.75 (CI 0.59-0.86), p = 0.020]. Conclusions: Using high-resolution BP data of 1 Hz, downsampling by averaging all BP values within 5-min intervals is essential to find relevant differences in systolic BPV, as noise can be avoided (confirmed by the significanc

BACKGROUND: Comprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far. OBJECTIVE: To analyze systematically the CSF profile in COVID-19. METHODS: Retrospective analysis of 150 lumbar punctures in 127 patients with PCR-proven COVID-19 and neurological symptoms seen at 17 European university centers RESULTS: The most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72-50.8]), which was present in 58/116 (50%) samples from patients without pre-/coexisting CNS diseases (group I). QAlb remained elevated > 14d (47.6%) and even > 30d (55.6%) after neurological onset. CSF total protein was elevated in 54/118 (45.8%) samples (median 65.35 mg/dl [45.3-240.4]) and strongly correlated with QAlb. The CSF white cell count (WCC) was increased in 14/128 (11%) samples (mostly lympho-monocytic; median 10 cells/µl, > 100 in only 4). An albuminocytological dissociation (ACD) was found in 43/115 (37.4%) samples. CSF L-lactate was increased in 26/109 (24%; median 3.04 mmol/l [2.2-4]). CSF-IgG was elevated in 50/100 (50%), but was of peripheral origin, since QIgG was normal in almost all cases, as were QIgA and QIgM. In 58/103 samples (56%) pattern 4 oligoclonal bands (OCB) compatible with systemic inflammation were present, while CSF-restricted OCB were found in only 2/103 (1.9%). SARS-CoV-2-CSF-PCR was negative in 76/76 samples. Routine CSF findings were normal in 35%. Cytokine levels were frequently elevated in the CSF (often associated with BCB dysfunction) and serum, partly remaining positive at high levels for weeks/months (939 tests). Of note, a positive SARS-CoV-2-IgG-antibody index (AI) was found in 2/19 (10.5%) patients which was associated with unusually high WCC in both of them and a strongly increased interleukin-6 (IL-6) index in one (not tested in the other). Anti-neuronal/anti-glial autoantibodies were mostly absent in t

In March 2020, at the onset of the coronavirus disease 2019 (COVID-19) pandemic in the United States, the Southern California Extracorporeal Membrane Oxygenation (ECMO) Consortium was formed. The consortium included physicians and coordinators from the 4 ECMO centers in San Diego County. Guidelines were created to ensure that ECMO was delivered equitably and in a resource effective manner across the county during the pandemic. A biomedical ethicist reviewed the guidelines to ensure ECMO use would provide maximal community benefit of this limited resource. The San Diego County Health and Human Services Agency further incorporated the guidelines into its plans for the allocation of scarce resources. The consortium held weekly video conferences to review countywide ECMO capacity (including census and staffing), share data, and discuss clinical practices and difficult cases. Equipment exchanges between ECMO centers maximized regional capacity. From March 1 to November 30, 2020, consortium participants placed 97 patients on ECMO. No eligible patients were denied ECMO due to lack of resources or capacity. The Southern California ECMO Consortium may serve as a model for other communities seeking to optimize ECMO resources during the current COVID-19 or future pandemics.

Purpose The COVID-19 pandemic has transformed medical care worldwide. General surgery has been affected in elective procedures, yet the implications for emergency surgery are unclear. The current study analyzes the effect of the COVID-19 lockdown in spring 2020 on appendicitis treatment in Germany. Methods Hospitals that provided emergency surgical care during the COVID-19 lockdown were invited to participate. All patients diagnosed with appendicitis during the lockdown period (10 weeks) and, as a comparison group, patients from the same period in 2019 were analyzed. Clinical and laboratory parameters, intraoperative and pathological findings, and postoperative outcomes were analyzed. Results A total of 1915 appendectomies from 41 surgical departments in Germany were included. Compared to 2019 the number of appendectomies decreased by 13.5% (1.027 to 888, p=0.003) during the first 2020 COVID-19 lockdown. The delay between the onset of symptoms and medical consultation was substantially longer in the COVID-19 risk group and for the elderly. The rate of complicated appendicitis increased (58.2 to 64.4%), while the absolute number of complicated appendicitis decreased from 597 to 569, (p=0.012). The rate of negative appendectomies decreased significantly (6.7 to 4.6%; p=0.012). Overall postoperative morbidity and mortality, however, did not change. Conclusion The COVID-19 lockdown had significant effects on abdominal emergency surgery in Germany. These seem to result from a stricter selection and a longer waiting time between the onset of symptoms and medical consultation for risk patients. However, the standard of emergency surgical care in Germany was maintained.

TNF-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL-R2) can induce apoptosis in cancer cells upon crosslinking by TRAIL. However, TRAIL-R2 is highly expressed by many cancers suggesting pro-tumor functions. Indeed, TRAIL/TRAIL-R2 also activate pro-inflammatory pathways enhancing tumor cell invasion, migration, and proliferation. In addition, nuclear TRAIL-R2 (nTRAIL-R2) promotes malignancy by inhibiting miRNA let-7-maturation. Here, we show that TRAIL-R2 interacts with the tumor suppressor protein p53 in the nucleus, assigning a novel pro-tumor function to TRAIL-R2. Knockdown of TRAIL-R2 in p53 wild-type cells increases the half-life of p53 and the expression of its target genes, whereas its re-expression decreases p53 protein levels. Interestingly, TRAIL-R2 also interacts with promyelocytic leukemia protein (PML), a major regulator of p53 stability. PML-nuclear bodies are also the main sites of TRAIL-R2/p53 co-localization. Notably, knockdown or destruction of PML abolishes the TRAIL-R2-mediated regulation of p53 levels. In summary, our finding that nTRAIL-R2 facilitates p53 degradation and thereby negatively regulates p53 target gene expression provides insight into an oncogenic role of TRAIL-R2 in tumorigenesis that particularly manifests in p53 wild-type tumors.

The nonlinear interaction of copropagating optical solitons enables a large variety of intriguing bound-states of light. We here investigate the interaction dynamics of two initially superimposed fundamental solitons at distinctly different frequencies. Both pulses are located in distinct domains of anomalous dispersion, separated by an interjacent domain of normal dispersion, so that group velocity matching can be achieved despite a vast frequency gap. We demonstrate the existence of two regions with different dynamical behavior. For small velocity mismatch we observe a domain in which a single heteronuclear pulse compound is formed, which is distinct from the usual concept of soliton molecules. The binding mechanism is realized by the mutual cross phase modulation of the interacting pulses. For large velocity mismatch both pulses escape their mutual binding and move away from each other. The crossover phase between these two cases exhibits two localized states with different velocity, consisting of a strong trapping pulse and weak trapped pulse. We detail a simplified theoretical approach which accurately estimates the parameter range in which compound states are formed. This trapping-to-escape transition allows to study the limits of pulse-bonding as a fundamental phenomenon in nonlinear optics, opening up new perspectives for the all-optical manipulation of light by light.

Cyanide, among with NOₓ, CO₂, and CO, is one of the adverse compounds that form in the ironmaking and steelmaking industry. High-temperature processes are suitable environments for cyanide formation, and cyanide can form as a result of recombination in electric arc plasma. Even though the cyanides might not survive e.g. the post-combustion process, understanding the formation mechanisms of hazardous materials in the steelmaking industry is important. In this work, the recombination of cyanide in a pilot-scale AC electric arc furnace is studied with optical emissions from the CN molecule. The results show how the optical emissions from the cyanide change in different process steps. Electric input, plasma temperature, and interaction of the arc with solid charge material were observed to have an impact on the CN signal. Additionally, equilibrium composition computation highlights how different sources of carbon change the recombination rate and that the highest recombination occurs at 6821 K.

A Barker sequence is a binary sequence for which all nontrivial aperiodic autocorrelations are either 0, 1 or -1. The only known Barker sequences have length 2, 3, 4, 5, 7, 11 or 13. It is an old conjecture that no longer Barker sequences exist and in fact, there is an overwhelming evidence for this conjecture. For binary sequences of odd length, this conjecture is known to be true, whereas for even length it is still open, whether a Barker sequence of even length greater 4 exists. Similar to the well-known fact that a Barker sequence of odd length is necessarily skew-symmetric, we show that in the case of even length there is also a form of symmetry albeit weaker. In order to exploit this symmetry, we derive different formulas for the calculation of the aperiodic correlation. We prove by using only elementary methods that there is no Barker sequence of even length n>4 with $C_{1}=C_{3}=\cdots=C_{\frac{n}{2}-1}$, where $C_{k}$ denotes the $k$th aperiodic autocorrelation of the sequence., Comment: 8 pages, no figures

Secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH-SBI) contributes to poor outcomes in patients after rupture of an intracranial aneurysm. The lack of diagnostic biomarkers and novel drug targets represent an unmet need. The aim of this study was to investigate the clinical and pathophysiological association between cerebrospinal fluid hemoglobin (CSF-Hb) and SAH-SBI. In a cohort of 47 patients, we collected daily CSF-samples within 14 days after aneurysm rupture. There was very strong evidence for a positive association between spectrophotometrically determined CSF-Hb and SAH-SBI. The accuracy of CSF-Hb to monitor for SAH-SBI markedly exceeded that of established methods (AUC: 0.89 [0.85-0.92]). Temporal proteome analysis revealed erythrolysis accompanied by an adaptive macrophage response as the two dominant biological processes in the CSF-space after aneurysm rupture. Ex-vivo experiments on the vasoconstrictive and oxidative potential of Hb revealed critical inflection points overlapping CSF-Hb thresholds in patients with SAH-SBI. Selective depletion and in-solution neutralization by haptoglobin or hemopexin efficiently attenuated the vasoconstrictive and lipid peroxidation activities of CSF-Hb. Collectively, the clinical association between high CSF-Hb levels and SAH-SBI, the underlying pathophysiological rationale, and the favorable effects of haptoglobin and hemopexin in ex-vivo experiments position CSF-Hb as a highly attractive biomarker and potential drug target.

Background: Nimodipine is routinely administered in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the effect of nimodipine on oxygen exchange in the lungs is insufficiently explored. Methods: The study explored nimodipine medication in artificially ventilated patients with aSAH. The data collection period was divided into nimodipine-dependent (ND) and nimodipine-independent (NID) periods. Values for arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2) were collected and compared between the periods. Patients were divided in those with lung injury (LI), defined as median Horowitz index (PaO2/FiO2) ≤40 kPa (≤300 mmHg), and without and in those with lower respiratory tract infection (LRTI) and without. Results: A total of 53 out of 150 patients were artificially ventilated, and in 29 patients, the Horowitz index could be compared between ND and NID periods. A linear mixed model showed that during ND period the Horowitz index was 2.3 kPa (95% CI, 1.0-3.5 kPa, P<0.001) lower when compared to NID period. The model suggested that in the presence of LI, ND period is associated with a decrease of the index by 2.8 kPa (95% CI, 1.2-4.3 kPa, P<0.001). The decrease was more pronounced with LRTI than without: 3.4 kPa (95% CI, 0.8-6.1 kPa) vs. 2.1 kPa (95% CI, 0.7-3.4 kPa), P=0.011 and P=0.002, respectively. Conclusions: In patients with LI or LRTI in the context of aSAH, pulmonary function may worsen with nimodipine treatment. The drop of 2 to 3 kPa of the Horowitz index in patients with no lung pathology may not outweigh the benefits of nimodipine. However, in individuals with concomitant lung injury, the effect may be clinically relevant. Keywords: Aneurysmal subarachnoid hemorrhage; Ca-channel blocker; Intrapulmonary shunt; Lung injury; Nimodipine; Pulmonary function.

Recognition of typical patterns of brain response to external stimuli using near-infrared spectroscopy (fNIRS) may become a gateway to detecting covert consciousness in clinically unresponsive patients. This is the first fNIRS study on the cortical hemodynamic response to favorite music using a frequency domain approach. The aim of this study was to identify a possible marker of cognitive response in healthy subjects by investigating variations in the oscillatory signal of fNIRS in the spectral regions of low-frequency (LFO) and very-low-frequency oscillations (VLFO). The experiment consisted of two periods of exposure to preferred music, preceded and followed by a resting phase. Spectral power in the LFO region increased in all the subjects after the first exposure to music and decreased again in the subsequent resting phase. After the second music exposure, the increase in LFO spectral power was less distinct. Changes in LFO spectral power were more after first music exposure and the repetition-related habituation effect strongly suggest a cerebral origin of the fNIRS signal. Recognition of typical patterns of brain response to specific environmental stimulation is a required step for the concrete validation of a fNIRS-based diagnostic tool.

Efficient all-optical switching is a challenging task as photons are bosons and cannot immediately interact with each other. Consequently, one has to resort to nonlinear optical interactions, with the Kerr gate being the classical example. However, the latter requires strong pulses to switch weaker ones. Numerous approaches have been investigated to overcome the resulting lack of fan-out capability of all-optical switches, most of which relied on types of resonant enhancement of light-matter interaction. Here we experimentally demonstrate a novel approach that utilizes switching between different portions of soliton fission induced supercontinua, exploiting an optical event horizon. This concept enables a high switching efficiency and contrast in a dissipation free setting. Our approach enables fan-out, does not require critical biasing, and is at least partially cascadable. Controlling complex soliton dynamics paves the way towards building all-optical logic gates with advanced functionalities., Peer Reviewed