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Maintenance of autonomic homeostasis is continuously calibrated by sensory fibers of the vagus nerve and sympathetic chain that convey compound action potentials (CAPs) to the central nervous system. Lipopolysaccharide (LPS) intravenous challenge reliably elicits a robust inflammatory response that can resemble systemic inflammation and acute endotoxemia. Here, we administered LPS intravenously in nine healthy subjects while recording ventral cervical magnetoneurography (vcMNG)-derived CAPs at the rostral Right Nodose Ganglion (RNG) and the caudal Right Carotid Artery (RCA) with optically pumped magnetometers (OPM). We observed vcMNG RNG and RCA neural firing rates that tracked changes in TNF-α levels in the systemic circulation. Further, endotype subgroups based on high and low IL-6 responders segregate RNG CAP frequency (at 30-120 min) and based on high and low IL-10 response discriminate RCA CAP frequency (at 0-30 min). These vcMNG tools may enhance understanding and management of the neuroimmune axis that can guide personalized treatment based on an individuals distinct endophenotype.

Abstract When evidence-based policymaking is so often mired in disagreement and controversy, how can we know if the process is meeting its stated goals? We develop a novel mathematical model to study disagreements about adequate knowledge utilization, like those regarding wild horse culling, shark drumlines and facemask policies during pandemics. We find that, when stakeholders disagree, it is frequently impossible to tell whether any party is at fault. We demonstrate the need for a distinctive kind of transparency in evidence-based policymaking, which we call transparency of reasoning. Such transparency is critical to the success of the evidence-based policy movement, as without it, we will be unable to tell whether in any instance a policy was in fact based on evidence.

Abstract Maintenance of autonomic homeostasis is continuously calibrated by sensory fibers of the vagus nerve and sympathetic chain that convey compound action potentials (CAPs) to the central nervous system. Lipopolysaccharide (LPS) intravenous challenge reliably elicits a robust inflammatory response that can resemble systemic inflammation and acute endotoxemia. Here, we administered LPS intravenously in nine healthy subjects while recording ventral cervical magnetoneurography (vcMNG)-derived CAPs at the rostral Right Nodose Ganglion (RNG) and the caudal Right Carotid Artery (RCA) with optically pumped magnetometers (OPM). We observed vcMNG RNG and RCA neural firing rates that tracked changes in TNF-α levels in the systemic circulation. Further, endotype subgroups based on high and low IL-6 responders segregate RNG CAP frequency (at 30-120 min) and based on high and low IL-10 response discriminate RCA CAP frequency (at 0-30 min). These vcMNG tools may enhance understanding and management of the neuroimmune axis that can guide personalized treatment based on an individual’s distinct endophenotype.

Aim of the study: Although neonatal resuscitation is rare, and high-risk births usually occur in specialised centres, unexpected resuscitation measures may be necessary during births that are initially considered low-risk. This survey assessed the practices of healthcare providers in Austrian hospitals for postnatal resuscitation and evaluated their self-assessed airway management skills for newborns. Methods: An online survey was distributed to all staff members responsible for the postnatal care of newborns in hospitals with obstetrics in Austria through the heads of departments (paediatrics, obstetrics, and anaesthesiology). The results are presented in terms of hospital care level and birth volume. Results: In total, 79.5 % of all hospitals with maternity units in Austria participated in the survey. Preparedness was found to be improved with the level of care provided by the hospital. Overall, 50.4 % of the respondents did not feel adequately prepared for neonatal emergencies, and 35.0 % rated their face mask ventilation skills as insufficient. According to the survey results in 61.3 % of included hospitals or 52.5 % of births in Austria, safe endotracheal intubation cannot be provided. Conclusion: A significant proportion of healthcare workers in Austria responsible for postnatal newborn care do not feel adequately prepared for newborn emergencies.

Background Evidence-based policymaking is a paradigm aimed at increasing the use of evidence by actors involved in policymaking processes. The COVID-19 pandemic highlighted a heavy reliance on emerging evidence for policymaking during emergencies.Objective This study describes the focus and types of evidence in journal articles self-described as relevant to policymaking using the COVID-19 pandemic as a case study, identifying gaps in evidence and highlighting author stated perceived biases specifically in evidence-based policy making.Design Evidence mapping.Data sources We systematically searched SCOPUS, PubMed and LexisNexis for literature identifying policy-relevant evidence available on the COVID-19 pandemic.Eligibility criteria The study included only peer-reviewed literature identified as ‘article’, ‘book chapter’, ‘review’ covering the period from January 2020 to December 2022. Inclusion criteria required that articles have an abstract, authorship attribution and are written in English.Data extraction and synthesis A minimum of two authors independently extracted and coded for every level and final outputs were compared for consistency.Results A total of 213 articles met the inclusion criteria and were reviewed in this study. Lead authorship affiliations were from 50 countries with 70% of the outputs from developed economies including USA (20.2%), UK (18.3%) and Australia (7.5%). The most common purpose of the articles was the presentation of research findings the authors considered of relevance to policy (60.1%), followed by work that examined the impact of policy (28.6%) or highlighted or supported a policy need (22.5%), while some papers had multiple stated purposes. The most common challenges in policymaking identified by the authors of the reviewed papers were process failures and poor evidence utilisation during policymaking.Conclusions The evidence map identified the need for an interdisciplinary policy approach involving relevant stakeholders and driven by quality research as a progressive step towards prevention of future public health crises/pandemics.

Abstract Background The use of cerebral magnetic resonance imaging (MRI) in observational studies has increased exponentially in recent years, making it critical to provide details about the study sample, image processing, and extracted imaging markers to validate and replicate study results. This article reviews the cerebral MRI dataset from the now-completed BiDirect cohort study, as an update and extension of the feasibility report published after the first two examination time points. Methods We report the sample and flow of participants spanning four study sessions and twelve years. In addition, we provide details on the acquisition protocol; the processing pipelines, including standardization and quality control methods; and the analytical tools used and markers available. Results All data were collected from 2010 to 2021 at a single site in Münster, Germany, starting with a population of 2,257 participants at baseline in 3 different cohorts: a population-based cohort (n = 911 at baseline, 672 with MRI data), patients diagnosed with depression (n = 999, 736 with MRI data), and patients with manifest cardiovascular disease (n = 347, 52 with MRI data). During the study period, a total of 4,315 MRI sessions were performed, and over 535 participants underwent MRI at all 4 time points. Conclusions Images were converted to Brain Imaging Data Structure (a standard for organizing and describing neuroimaging data) and analyzed using common tools, such as CAT12, FSL, Freesurfer, and BIANCA to extract imaging biomarkers. The BiDirect study comprises a thoroughly phenotyped study population with structural and functional MRI data. Relevance statement The BiDirect Study includes a population-based sample and two patient-based samples whose MRI data can help answer numerous neuropsychiatric and cardiovascular research questions. Key points • The BiDirect study included characterized patient- and population-based cohorts with MRI data. • Data were standardized to Brain Imaging Data Structure and processed with commonly available software. • MRI data and markers are available upon request. Graphical Abstract

Introduction: Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of “trial-ineligible” and “potentially trial-eligible” patients. Methods: Data from the prospective, clinical research platform CRISP were used to compare patient characteristics, treatment, and outcome of patients with programmed cell death-ligand 1 tumor proportion score greater than or equal to 50% tumors treated with pembrolizumab monotherapy who are deemed either “potentially trial-eligible” or “trial-ineligible” according to inclusion and exclusion criteria of the registrational studies (KEYNOTE-024 and -042). Results: Of 746 patients included, 343 patients (46.0%) were classified as “trial-ineligible” and had significantly worse outcomes compared with “potentially trial-eligible” patients (n = 403, 54.0%): median progression-free survival: 6.2 (95% confidence interval [CI]: 5.2–8.4) versus 10.3 (95% CI: 8.4–13.8) months, hazard ratio (trial-ineligible versus potentially trial-eligible) of 1.43 (95% CI: 1.19–1.72), p less than 0.001; median overall survival: 15.9 (95% CI: 11.4–20.3) versus 25.3 (95% CI: 19.8–30.4) months, hazard ratio of 1.36 (95% CI: 1.10–1.67), p equals 0.004. Conclusions: Our data reveal that a considerable proportion of patients with mNSCLC are not eligible to participate in a clinical trial and were found to have worse outcomes than potentially trial-eligible patients, whose outcomes were comparable with those obtained from pivotal clinical trials. This is of substantial clinical relevance for physicians discussing outcomes to be expected with their patients and stresses the need for real-world effectiveness analyses.

Substrate facies monitoring is critical for the understanding of fluvial geomorphologic and ecohydraulic patterns and processes. However, direct substrate measurement is time-consuming and subjected to data sparsity because of small sample, size, and limited data collections within an area of interest, which make it difficult to capture facies patterns. Most new experimental studies focus on mapping substrate based on median grain size of a specific grain size class using automatic or semiautomatic photosieving techniques. This study aimed to develop and apply a method to accurately predict size-mixture facies patterns on exposed riverbeds with minimal ground truth plots (100) using airborne lidar and machine learning. The selected testbed river was a 37.5-km stretch of the regulated lower Yuba River in California, USA, mapped at sub-meter resolution in 2017. First, we designed a grid-by-point grain size sampling method and binned grain sizes into representative mixtures, such as fine or large gravel, to assign subaerial facies labels. Second, we classified facies based on a multivariate cluster analysis. Third, we generated 15 lidar-derived topographic and spectral predictors. Six distinct size-mixture facies were identified from field data and a seventh, pure sand facies, from UAV data. A random forest predictive model with an 86% 10-fold cross-validation accuracy was applied to produce a facies map at the 1.54 m pixel scale. The detrended elevation was identified as the most important variable for predicting facies spatial patterning, followed by baseflow, wetted area proximity, and green lidar intensity. We conclude that machine learning combined with intensity lidar data is highly effective for distinguishing mixed classes of substrates. Ultimately, the new substrate mixture-binning approach also provides novel insights into the arrangement of river sediment facies patterns.

Abstract Global change alters hydro-climatic conditions, affects land use, and contributes to more frequent droughts and floods. Large artificial reservoirs may effectively alleviate hydro-climatic extremes, but their storage capacities are threatened by sedimentation processes, which in turn are exacerbated by land use change. Envisioning strategies for sustainable reservoir management requires interdisciplinary model chains to emulate key processes driving sedimentation under global change scenarios. Therefore, we introduce a model chain for the long-term prediction of complex three-dimensional (3d) reservoir sedimentation considering concurrent catchment, hydro-climatic, and land-use conditions. Applied to a mountainous Mediterranean catchment, the model chain predicts increased sediment production and decreased discharge for high and medium emission pathways. Increased winter precipitation, accompanied by a transition from snowfall to rainfall, is projected to aggravate reduced summer precipitation, emphasizing a growing need for reservoirs. Additionally, higher winter precipitation proliferates sediment production and reservoir sedimentation. Land use change can outweigh the increased reservoir sedimentation originating from hydro-climatic change, which highlights the significance of localized actions to reduce sediment production. Finally, a 3d hydro-morphodynamic model provides insights into interactions between global change and reservoir sedimentation with spatially explicit information on future sedimentation patterns facilitating the implementation of management strategies.

Electrodiagnosis is routinely integrated into clinical neurophysiology practice for peripheral nerve disease diagnoses, such as neuropathy, demyelinating disorders, nerve entrapment/impingement, plexopathy, or radiculopathy. Measured with conventional surface electrodes, the propagation of peripheral nerve action potentials along a nerve is the result of ionic current flow which, according to Ampere's Law, generates a small magnetic field that is also detected as an "action current" by magnetometers, such as superconducting quantum interference device (SQUID) Magnetoencephalography (MEG) systems. Optically pumped magnetometers (OPMs) are an emerging class of quantum magnetic sensors with a demonstrated sensitivity at the 1 fT/√Hz level, capable of cortical action current detection. But OPMs were ostensibly constrained to low bandwidth therefore precluding their use in peripheral nerve electrodiagnosis. With careful OPM bandwidth characterization, we hypothesized OPMs may also detect compound action current signatures consistent with both Sensory Nerve Action Potential (SNAP) and the Hoffmann Reflex (H-Reflex). In as much, our work confirms OPMs enabled with expanded bandwidth can detect the magnetic signature of both the SNAP and H-Reflex. Taken together, OPMs now show potential as an emerging electrodiagnostic tool.

The increasing volume of personal motorized vehicles (PMVs) in cities has become a serious issue leading to congestion, noise, air pollution and high land consumption. To ensure the sustainability of urban transportation, it is imperative to transition the current transportation paradigm toward a more sustainable state. Transitions within socio-technical systems often arise from niche innovation. Therefore, this paper pursues the technical optimization of such a niche innovation by applying a technical sustainability perspective on an innovative mobility and logistics concept within a case study. This case study is based on a centrally managed connected, automated, shared and electric (CASE) vehicle fleet which might replace PMV use in urban city centers of the future. The key technical system components of the envisioned mobility and logistics concept are analyzed and optimized with regard to economic, ecological and social sustainability dimensions to maximize the overall sustainability of the ecosystem. Specifically, this paper identifies key challenges and proposes possible solutions across the vehicle components as well as the orchestration of the vehicles’ operations within the envisioned mobility and logistics concept. Thereby, the case study gives an example of how different engineering disciplines can contribute to different sustainability dimensions, highlighting the interdependences. Finally, the discussion concludes that the early integration of sustainability considerations in the technical optimization efforts of innovative transportation systems can provide an important building block for the transition of the current transportation paradigm to a more sustainable state.

Electromyostimulation (EMS) is an up-and-coming training method that demands further fundamental research regarding its safety and efficacy. To investigate the influence of different stimulation parameters, electrode positions and electrode sizes on the resulting voltage in the tissue, a tissue mimicking phantom is needed. Therefore, this study describes the fabrication of a hydrogel arm phantom for EMS applications with the tissue layers of skin, fat, blood and muscle. The phantom was dielectrically validated in the frequency range of 20 Hz to 100 Hz. We also conducted electromyography (EMG) recordings during EMS on the phantom and compared them with the same measurements on a human arm. The phantom reproduces the dielectric properties of the tissues with deviations ranging from 0.8% to more than 100%. Although we found it difficult to find a compromise between mimicking the permittivity and electrical conductivity at the same time, the EMS–EMG measurements showed similar waveforms (1.9–9.5% deviation) in the phantom and human. Our research contributes to the field of dielectric tissue phantoms, as it proposes a multilayer arm phantom for EMS applications. Consequently, the phantom can be used for initial EMS investigations, but future research should focus on further improving the dielectric properties.

Abstract Background Tuberculous meningitis, a rare but severe form of extrapulmonary tuberculosis, frequently affects cranial nerves. While nerves III, VI and VII are commonly involved, involvement of caudal cranial nerves is rarely described. Here, we report a rare case of bilateral vocal cord palsy secondary to caudal cranial nerve involvement in tuberculous meningoencephalitis, that occurred in Germany, a country with low tuberculosis incidence. Case presentation A 71-year-old woman was transferred for further treatment of hydrocephalus as a complication of presumed bacterial meningitis with unknown pathogen at that time. Because of decreased consciousness, intubation was performed and an empiric antibiotic therapy with ampicillin, ceftriaxone and acyclovir was initiated. Upon admission to our hospital, an external ventricular drainage was placed. Cerebrospinal fluid analysis revealed Mycobacterium tuberculosis as the causative pathogen, and antitubercular treatment was initiated. Extubation was possible one week after admission. Eleven days later, the patient developed inspiratory stridor that worsened within a few hours. Flexible endoscopic evaluation of swallowing (FEES) revealed new-onset bilateral vocal cord palsy as the cause of respiratory distress, which required re-intubation and tracheostomy. The bilateral vocal cord palsy persisted despite continued antitubercular therapy on the follow-up examination. Conclusion Considering the aetiology of infectious meningitis, cranial nerve palsies may be suggestive for tuberculous meningitis as underlying disease given their rarity in other bacterial forms of meningitis. Nevertheless, intracranial involvement of inferior cranial nerves is rare even in this specific entity, as only extracranial lesions of inferior cranial nerves have been reported in tuberculosis. With this report of a rare case of bilateral vocal cord palsy due to intracranial involvement of the vagal nerves, we emphasize the importance of timely initiation of treatment for tuberculous meningitis. This may help to prevent serious complications and associated poor outcome since the response to anti-tuberculosis therapy may be limited.

Abstract The placement of wood in rivers is a common restoration method used to locally affect hydraulic and morphologic conditions to create habitat. Laboratory experiments demonstrated that wood placements can also promote surface declogging, that is, removal of fine sediment from a gravel bed, thereby restoring spawning grounds for fish. Logs of different size and submergence level were placed on a gravel bed clogged with fines. Surface declogging was observed in regions of elevated turbulence in the log wake and elevated velocity adjacent to the log. A criteria for declogging was identified based on a modified non‐dimensional Shields parameter combining mean and turbulent velocity at the bed. The footprint of declogged bed scaled with log dimensions. Emergent logs produced a larger declogging footprint compared to submerged logs of the same length, due to their stronger influence on the flow field. Logs were also shown to prevent clogging over similar areas.

Neste estudo se aborda o uso de róticos em posição de coda na Região Metropolitana de Porto Alegre, particularmente a articulação retroflexa, na perspectiva da Sociolinguística Variacionista (Labov, 1966, 1972). O estudo é composto por 45 entrevistas do corpus Ricardo-Schwindt, abrangendo 5 cidades da região. Os resultados indicaram baixa presença do rótico retroflexo na Região Metropolitana em comparação com outras variedades do português brasileiro, mas um aumento significativo quando comparado ao seu uso na capital, Porto Alegre, nas décadas de 1980 e 1990. A pronúncia retroflexa parece estar relacionada, entre outros aspectos, a contextos que compartilham propriedades fonéticas com essa variante, sugerindo alguma motivação assimilatória para sua emergência. Identificaram-se, além disso, diferenças significativas no uso do retroflexo entre as cidades analisadas.

ObjectiveMechanical thrombectomy (MT) has become the standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO). First-pass (FP) reperfusion of the occluded vessel and fewer passes with stent retrievers show improvement in functional outcomes in stroke patients, while higher numbers of passes are associated with higher complication rates and worse outcomes. Studies indicate that a larger size of the stent-retriever is associated with a higher rate of first-pass reperfusion and improved clinical outcomes. In this retrospective study, we investigated the clinical performance of a recently developed and one of the largest stent-retrievers available in the treatment of LVO (pRESET 6-50, phenox GmbH, Bochum).Materials and methodsAll consecutive patients with ischemic stroke due to proximal large vessel occlusion treated with MT using the pRESET 6-50 stent-retriever in two tertiary stroke centers between 09/2021 and 07/2022 were included in this study. The reperfusion rate after MT was quantified by the modified thrombolysis in cerebral infarction (mTICI) score, and functional neurological outcome was evaluated with the National Institutes of Health Stroke Scale (NIHSS) score and the major early neurological recovery (mENR) rate after 24 h. Successful FP reperfusion was defined as mTICI ≥ 2b. Successful and complete reperfusion were defined as mTICI ≥ 2b and mTICI ≥ 2c, respectively.ResultsIn total, 98 patients (52 men and 46 women) with a median age of 75 (range 25–95 years) were included. A total of 70 (72%) patients presented with an occlusion of the middle cerebral artery (MCA) in the M1 segment, 6 (6%) patients with an occlusion of the M2 segment, 17 (17%) patients with an occlusion of the internal carotid artery (ICA), and 5 (5%) patients with an occlusion of the obstructed basilar artery (BA). Successful FP reperfusion was achieved in 58 patients (62%). Successful and complete reperfusion were achieved in 95 (97%) and 82 (83%) patients, respectively. The median National Institutes of Health Stroke Scale (NIHSS) in all treated patients improved from 17 to 7.5. Major early neurological recovery (mENR) was observed in 34 patients (35.1%).ConclusionMT with the pRESET 6-50 stent-retriever achieves high successful first-pass and final reperfusion rates in patients with AIS and LVO. The results of this study support the thesis to use large-format stent-retriever in proximal vessel occlusion MT whenever feasible in order to improve high FP and final reperfusion rate, which are known predictors of good clinical outcome.

Rivers provide dynamic habitats with ecological niches, particularly in their mobile sand, gravel, and cobble riverbed patches that create an active hyporheic zone. Natural or artificial deposition of fine sediment may clog the porous matrix of the hyporheic zone, impairing exchange processes between the subsurface and surface water. Clogging reduces the permeability of the sediment matrix, thus degrading the ecological functionality of the hyporheic zone. Once clogged, the ecological functions may be recovered through active stream restoration, which requires considerate site assessment. To this end, clogging is typically assessed by expert opinion of substrate characteristics including grain size characteristics, porosity, hydraulic conductivity, and interstitial oxygen content. To overcome limitations of expert assessment, such as subjectivity expressed in noisy decision-making, this study introduces a novel fuzzy-logic method based on physically sound rules. The method provides quantitative indicators for clogging and declogging to evaluate the effectiveness of stream restoration. We applied the fuzzy-logic method to test whether the placement of large wood, a common restoration practice, can locally prevent or reduce clogging. Two measurement series from before and after a morphologically effective flood suggested that large wood placements perpendicular to the flow generate elevated amounts of declogging. The tested logs caused a greater amount of declogging within their region of influence than observed at a reference point. The effect was stronger for a log emergent at baseflow. The declogging assessment showed that the novel fuzzy-logic indicators can reasonably overcome subjective judgment by accounting for multi-variate quantitative changes rather than individual parameter trends.