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Electrospinning is used for producing nonwovens for medical polymer-based implants, such as prosthetic valves or covered scaffolds. In this study, nonwovens for prosthetic venous valves are investigated regarding their morphology and mechanics in physiological medium. Spinning molds were developed based on previous venous valve leaflet designs, 3D printed in different sizes and covered with electrospun nonwovens. Samples were stored in a physiological 0.9% saline at 37°C to investigate the influence of fiber rearrangement and swelling in medium for several weeks. Two different nonwovens of thermoplastic silicone-based polycarbonaturethane (TSPCU) were compared. Tensile test results show that storage in medium has a relevant influence on the mechanical properties. SEM images of TSPCU show substantially increased fiber diameters after 8 days stored in medium. After detaching the valve leaflet nonwovens from the molds, shrinkage of the material of approximately 12% was detected. A suitable valve size could be identified for joining with the stent structure into an interventional prosthetic venous valve. The results demonstrate the influence of storage conditions on the morphological and mechanical properties of electrospun TSPCU nonwovens. For development and dimensioning of venous valve leaflets, this change in mechanical behavior and possible shrinkage of the material has to be considered.

A two-step method for investigating the stiffnesses and failure loads of vertebral bodies is presented. It is based on the representation of the spine in a global finite element model of structural elements. A detailed model of two interconnected vertebrae and an intervertebral disc was implemented. Calculations on this model are shown which illustrate the dependencies of structural stiffnesses on vertebral body properties. These structural stiffnesses can then be used to represent the spine in the global model.

The presented three different balloon dilation devices for treating Eustachian tube dysfunction were compared regarding their geometries and designs. The balloon dilation behaviour was investigated by an in vitro test setup consisting of a test chamber with 37 °C water, a 2-axis laser scanner and a pressure controller. All balloons could be properly dilated up to the given nominal pressure (NP) or to rated burst pressure (RBP). The balloons reached their expected balloon diameter and length. The compliance data were 1.07 %/atm (TubaVent short), 1.16 %/atm (Acclarent Aera) and 1.28 %/atm (XprESS LoProfile). The measured profile and compliance data can be used for development of new devices for balloon dilation Eustachian tuboplasty.

Chronic venous insufficiency (CVI) is a common disease characterized by impaired venous drainage leading to congestion in the lower limbs. Currently, there are no artificial or biological venous valve prostheses commercially available. Previous minimally invasive design concepts failed to achieve sufficient long term results in animal or in vitro studies. The aim was to implement structural numerical simulation of clinically relevant loading cases for minimally invasive implantable venous valve prostheses. A bicuspid valve design was chosen as it showed superior results compared to tricuspid valves in previous studies. The selfexpanding support structure was developed by using diamond-shaped elements. Using finite-element analysis (FEA), various loading cases, including expansion and crimping of the stent structure and the release into a venous vessel, were simulated. A hyperelastic constitutive law for the vascular model was generated from uniaxial tensile test data of unfixated human vein walls. This study also compared numerical and experimental results regarding compliance and tensile tests to validate the vein material model. The calculated performance concerning expansion and crimping, as well as the release of the stent into a venous vessel, demonstrated the suitability of the stent design for minimally invasive application.

Introduction: Recent evidence suggests the blood-to-brain influx rate (K1) in TSPO PET imaging as a promising biomarker of blood-brain barrier (BBB) permeability alterations commonly associated with peripheral inflammation and heightened immune activity in the brain. However, standard compartmental modeling quantification is limited by the requirement of invasive and laborious procedures for extracting an arterial blood input function. In this study, we validate a simplified blood-free methodologic framework for K1 estimation by fitting the early phase tracer dynamics using a single irreversible compartment model and an image-derived input function (1T1K-IDIF). Methods: The method is tested on a multi-site dataset containing 177 PET studies from two TSPO tracers ([11C]PBR28 and [18F]DPA714). Firstly, 1T1K-IDIF K1 estimates were compared in terms of both bias and correlation with standard kinetic methodology. Then, the method was tested on an independent sample of [11C]PBR28 scans before and after inflammatory interferon-α challenge, and on test-retest dataset of [18F]DPA714 scans. Results: Comparison with standard kinetic methodology showed good-toexcellent intra-subject correlation for regional 1T1K-IDIF-K1 (ρintra = 0.93 ± 0.08), although the bias was variable depending on IDIF ability to approximate blood input functions (0.03-0.39 mL/cm3/min). 1T1K-IDIF-K1 unveiled a significant reduction of BBB permeability after inflammatory interferon-α challenge, replicating results from standard quantification. High intra-subject correlation (ρ = 0.97 ± 0.01) was reported between K1 estimates of test and retest scans. Discussion: This evidence supports 1T1K-IDIF as blood-free alternative to assess TSPO tracers' unidirectional blood brain clearance. K1 investigation could complement more traditional measures in TSPO studies, and even allow further mechanistic insight in the interpretation of TSPO signal. [ABSTRACT FROM AUTHOR]

Creativity and innovation are important inputs in the global knowledge economy. However, while the theoretical concepts and the measurement of creativity on the individual level have made considerable progress during the last decades, so-called sectoral approaches to measuring creativity and innovation on the level of aggregate units are less well developed. The article is the first to review and compare the different approaches of the most popular international creativity rankings. Analyzed sectors are countries, companies, and universities. It becomes apparent that company rankings, in particular, are virtually arbitrary, yet different country and university rankings show much higher correlations. Weaknesses in the rankings' operationalization and modeling of creativity and innovation measures, as well as potential improvements in methodology, are discussed in the context of the current debate in the literature.

Introduction: To date, there have only been provisional recommendations about the appropriate gestational weight gain in twin pregnancies. This study aimed to contribute evidence to this gap of knowledge. Material and methods: Using a cohort of 10 603 twin pregnancies delivered between 2000 and 2015 in the state of Hessen, Germany, the individual and combined impact of maternal body mass index and gestational weight gain on maternal and neonatal outcomes was analyzed using uni‐ and multivariable logistic regression models. The analysis used newly defined population‐based quartiles of gestational weight gain in women carrying twin pregnancies (Q1: <419.4 g/week [low weight gain], Q2–Q3: 419.4–692.3 g/week [optimal weight gain], Q4: >692.3 g/week [high weight gain]) and the World Health Organization body mass index classification. Results: Pre‐pregnancy body mass index ≥25 kg/m2 was associated with significantly increased rates of cesarean deliveries (aOR1.2, 95% CI: 1.01–1.41) and pregnancy‐induced hypertensive disorders (aOR 1.53, 95% CI: 1.11–2.1) but not with any adverse neonatal outcome. Perinatal mortality (aOR 2.23, 95% CI: 1.38–3.6), preterm birth (aOR 1.88, 95% CI: 1.58–2.25), APGAR′5 < 7 (aOR 1.61, 95% CI: 1.19–2.17) and admissions to the neonatal intensive care unit (aOR 1.6, CI: 1.38–1.85) were increased among women with low gestational weight gain. Rates of cesarean deliveries were high in both women with low (aOR 1.25, 95% CI: 1.05–1.48) and high gestational weight gain (aOR 1.17, 95% CI: 1.01–1.35). A high gestational weight gain was also associated with higher rates of hypertensive disorders in pregnancy (aOR 2.32, 95% CI: 1.79–3.02) and postpartum hemorrhage (aOR 1.72, 95%CI: 1.12–2.63). The risk of preterm birth, low Apgar scores and NICU admissions showed a converse linear relation with pre‐pregnancy body mass index in women with low gestational weight gain. Conclusions: In twin pregnancies, nonoptimal weekly maternal weight gain seems to be strongly associated with maternal and neonatal adverse outcomes. Since gestational weight gain is a modifiable risk factor, health care providers have the opportunity to counsel pregnant women with twins and target their care accordingly. Additional research to confirm the validity and generalizability of our findings in different populations is warranted. [ABSTRACT FROM AUTHOR]

Since the early 2000s, proposals to deliberately modify the Earth's climate have gained political traction as a controversial last resort measure against dangerous global warming. The article provides a 'longue durée' picture of such climate engineering proposals. It traces their historical trajectory from the late 1950s to their most recent arrival on mainstream climate policy agendas. This perspective suggests that the history of climate engineering unfolds not only along historically specific modes of understanding climatic change. It also corresponds to changing alliances between climate science and the state. By bringing together historical scholarship with contributions from sociology and science policy studies, the article sheds new light on the rise of climate engineering proposals. It recontextualizes these proposals within the bigger history of the political cultivation of climate science. This perspective highlights how deeply entwined efforts to understand and efforts to govern climatic change have always been. This article is categorized under:Climate, History, Society, Culture > Ideas and KnowledgeThe Social Status of Climate Change Knowledge > Sociology/Anthropology of Climate KnowledgeThe Social Status of Climate Change Knowledge > Knowledge and Practice [ABSTRACT FROM AUTHOR]

The brain is protected by the endothelial blood–brain barrier (BBB) that limits the access of micro‐organisms, tumour cells, immune cells and autoantibodies to the parenchyma. However, the classic model of disease spread across a disrupted BBB does not explain the focal distribution of lesions seen in a variety of neurological diseases and why lesions are frequently adjacent to the cerebrospinal fluid (CSF) spaces. We have critically reviewed the possible role of a blood–CSF–brain route as a disease entry pathway into the brain parenchyma. The initial step of this pathway is the transfer of pathogens or immune components from the blood into the CSF at the choroid plexuses, where the blood–CSF barrier (BCSFB) is located. The flow of CSF results in disease dissemination throughout the CSF spaces. Access to the brain parenchyma from the CSF can then occur across the ependymal layer at the ventricular surface or across the pial–glial barrier of the subarachnoid space and the Virchow–Robin spaces. We have reviewed the anatomy and physiology of the blood–CSF–brain pathway and the brain barriers controlling this process. We then summarised the evidence supporting this brain entry route in a cross‐section of neurological diseases including neuromyelitis optica, multiple sclerosis, neurosarcoidosis, neuropsychiatric lupus, cryptococcal infection and both solid and haematological tumours. This summary highlights the conditions that share the blood–CSF–brain pathway as a pathogenetic mechanism. These include the characteristic proximity of lesions to CSF, evidence of disruption of the brain barriers and the identification of significant pathology within the CSF. An improved understanding of pathological transfer through the CSF and across all brain barriers will inform on more effective and targeted treatments of primary and secondary diseases of the central nervous system. [ABSTRACT FROM AUTHOR]

An inherent tension between the global and the national frame of reference defines the modern research university. This seems to be the conflicting diagnosis of two recently published volumes on the matter: In their book on The University and the Global Knowledge Society, David J. Frank and John W. Meyer (2020) link the spectacular rise of the university to its lasting claim to generate "universalized truths" (Frank & Meyer 2020). John Aubrey Douglass and others (2021), in contrast, paint a decidedly different picture. In their volume on Neo-Nationalism and Universities, Douglass and eleven co-authors trace how universities have increasingly come under pressure by a recent wave of neo-nationalism that has challenged the very idea of the global research university right to its core. In presenting these contrasting accounts, the two volumes raise a number of pressing questions for science studies and higher education research more broadly: How do recent developments of neonationalism and populism connect to the longer history of national interests in science as a tool at the hand of the state? How do such nationalist tendencies play into, or counter, the global expansion of the university? And finally, how can we secure the transnational and open idea of a university in times when the specific organizations as well as their cultural core are threatened by national governments? To engage with these questions, this Review Symposium brings together an interdisciplinary group of scholars who discuss the two volumes and share their diverse perspectives on Universities between Inter- and Re-Nationalization. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance spectroscopy quantitatively monitors biomarkers of neuron-myelin coupling (N-acetylaspartate (NAA)), and inflammation (total creatine (tCr), total choline (tCho), myo-inositol (mI)) in the brain. Objective: This study aims to investigate how ocrelizumab and interferon beta-1a differentially affects imaging biomarkers of neuronal-myelin coupling and inflammation in patients with relapsing multiple sclerosis (MS). Methods: Forty patients with relapsing MS randomized to either treatment were scanned at 3T at baseline and weeks 24, 48, and 96 follow-up. Twenty-four healthy controls were scanned at weeks 0, 48, and 96. NAA, tCr, tCho, mI, and NAA/tCr were measured in a single large supra-ventricular voxel. Results: There was a time × treatment interaction in NAA/tCr (p = 0.04), primarily driven by opposing tCr trends between treatment groups after 48 weeks of treatment. Patients treated with ocrelizumab showed a possible decline in mI after week 48 week, and stable tCr and tCho levels. Conversely, the interferon beta-1a treated group showed possible increases in mI, tCr, and tCho over 96 weeks. Conclusions: Results from this exploratory study suggest that over 2 years, ocrelizumab reduces gliosis compared with interferon beta-1a, demonstrated by declining ml, and stable tCr and tCho. Ocrelizumab may improve the physiologic milieu by decreasing neurotoxic factors that are generated by inflammatory processes. [ABSTRACT FROM AUTHOR]

Ischemic stroke due to an acute occlusion of the extracranial internal carotid artery (eICA) is associated with high morbidity and mortality. The best treatment option remains unclear. This study aims to increase the available therapeutic experience documented for surgical recanalization of acute eICA occlusions. We retrospectively reviewed all hospital records of the University Hospital Jena between 2006 and 2018 to identified patients with acute ischemic stroke due to an occlusion of the eICA who underwent emergent surgical recanalization. We analyzed clinical data, surgical reports, imaging data, and outpatient records. The primary outcome parameter was the modified Rankin Scale (mRS) at 3 months. During the survey, 12 patients (mean age: 62.3 ± 10.8 years; range: 35-87) underwent emergent surgical recanalization for an acutely symptomatic eICA occlusion. All patients presented with neurological deficits with a mean National Institutes of Health Stroke Scale score at admission of 15.0 ± 5.1 (range 2-23). Patients were selected for surgery mainly due to the extent of the perfusion mismatch, while stroke severity and age were also considered. The median time from symptom onset to surgery was 309 ± 122 minutes (range 112-650 minutes). Complete recanalization was obtained in all 12 patients. No patient deteriorated postoperatively, no intracranial hemorrhage was observed, and no patient died in the following 3 months. Favorable outcomes (mRS: 0-2) after 3 months were achieved in 7 of 12 patients. The current study adds support to previous findings that the surgical recanalization of acute eICA occlusions is a possible and safe treatment option. However, a critical patient selection based on mismatch size in perfusion imaging is crucially important for successful treatment. [ABSTRACT FROM AUTHOR]

Creativity and innovation are important inputs in the global knowledge economy. However, while the theoretical concepts and the measurement of creativity on the individual level have made considerable progress during the last decades, so-called sectoral approaches to measuring creativity and innovation on the level of aggregate units are less well developed. The article is the first to review and compare the different approaches of the most popular international creativity rankings. Analyzed sectors are countries, companies, and universities. It becomes apparent that company rankings, in particular, are virtually arbitrary, yet different country and university rankings show much higher correlations. Weaknesses in the rankings’ operationalization and modeling of creativity and innovation measures, as well as potential improvements in methodology, are discussed in the context of the current debate in the literature. [ABSTRACT FROM AUTHOR]

Brain fluid clearance by pathways including the recently described paravascular glymphatic system is a critical homeostatic mechanism by which metabolic products, toxins, and other wastes are removed from the brain. Brain fluid clearance may be especially important after traumatic brain injury (TBI), when blood, neuronal debris, inflammatory cells, and other substances can be released and/or deposited. Using a non-invasive dynamic positron emission tomography (PET) method that models the rate at which an intravenously injected radiolabeled molecule (in this case 11 C-flumazenil) is cleared from ventricular cerebrospinal fluid (CSF), we estimated the overall efficiency of brain fluid clearance in humans who had experienced complicated-mild or moderate TBI 3-6 months before neuroimaging ( n  = 7) as compared to healthy controls ( n  = 9). While there was no significant difference in ventricular clearance between TBI subjects and controls, there was a significant group difference in dependence of ventricular clearance upon tracer delivery/blood flow to the ventricles. Specifically, in controls, ventricular clearance was highly, linearly dependent upon blood flow to the ventricle, but this relation was disrupted in TBI subjects. When accounting for blood flow and group-specific alterations in blood flow, ventricular clearance was slightly (non-significantly) increased in TBI subjects as compared to controls. Current results contrast with past studies showing reduced glymphatic function after TBI and are consistent with possible differential effects of TBI on glymphatic versus non-glymphatic clearance mechanisms. Further study using multi-modal methods capable of assessing and disentangling blood flow and different aspects of fluid clearance is needed to clarify clearance alterations after TBI., Competing Interests: No competing financial interests exist., (© Tracy Butler et al., 2024; Published by Mary Ann Liebert, Inc.)

Background: Recent studies have shown that choroid plexuses (CP) may be involved in the neuro-immune axes, playing a role in the interaction between the central and peripheral inflammation. Here we aimed to investigate CP volume alterations in depression and their associations with inflammation., Methods: 51 depressed participants (HDRS score > 13) and 25 age- and sex-matched healthy controls (HCs) from the Wellcome Trust NIMA consortium were re-analysed for the study. All the participants underwent full peripheral cytokine profiling and simultaneous [11C]PK11195 PET/structural MRI imaging for measuring neuroinflammation and CP volume respectively., Results: We found a significantly greater CP volume in depressed subjects compared to HCs (t (76) = +2.17) that was positively correlated with [ 11 C]PK11195 PET binding in the anterior cingulate cortex (r = 0.28, p = 0.02), prefrontal cortex (r = 0.24, p = 0.04), and insular cortex (r = 0.24, p = 0.04), but not with the peripheral inflammatory markers: CRP levels (r = 0.07, p = 0.53), IL-6 (r = -0.08, p = 0.61), and TNF-α (r = -0.06, p = 0.70). The CP volume correlated with the [ 11 C]PK11195 PET binding in CP (r = 0.34, p = 0.005). Integration of transcriptomic data from the Allen Human Brain Atlas with the brain map depicting the correlations between CP volume and PET imaging found significant gene enrichment for several pathways involved in neuroinflammatory response., Conclusion: This result supports the hypothesis that changes in brain barriers may cause reduction in solute exchanges between blood and CSF, disturbing the brain homeostasis and ultimately contributing to inflammation in depression. Given that CP anomalies have been recently detected in other brain disorders, these results may not be specific to depression and might extend to other conditions with a peripheral inflammatory component., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Immune mechanisms have been implicated in the pathogenesis of depression. Translocator protein (TSPO)-targeted positron emission tomography (PET) has been used to assess neuroinflammation in major depressive disorder. We aimed to 1) test the hypothesis of significant case-control differences in TSPO binding in the anterior cingulate cortex, prefrontal cortex, and insula regions; and 2) explore the relationship between cerebral TSPO binding and peripheral blood C-reactive protein (CRP) concentration., Methods: A total of 51 depressed subjects with Hamilton Depression Rating Scale score >13 (median 17; interquartile range, 16-22) and 25 healthy control subjects underwent dynamic brain 11 C-PK11195 PET and peripheral blood immune marker characterization. Depressed subjects were divided into high CRP (>3 mg/L; n = 20) and low CRP (<3 mg/L; n = 31)., Results: Across the three regions, TSPO binding was significantly increased in depressed versus control subjects (η 2 p  = .09; F 1,71  = 6.97, p = .01), which was not influenced by body mass index. The case-control difference was greatest in the anterior cingulate cortex (d = 0.49; t 74  = 2.00, p = .03) and not significant in the prefrontal cortex or insula (d = 0.27 and d = 0.36, respectively). Following CRP stratification, significantly higher TSPO binding was observed in low-CRP depression compared with controls (d = 0.53; t 54  = 1.96, p = .03). These effect sizes are comparable to prior major depressive disorder case-control TSPO PET data. No significant correlations were observed between TSPO and CRP measures., Conclusions: Consistent with previous findings, there is a modest increase in TSPO binding in depressed patients compared with healthy control subjects. The lack of a significant correlation between brain TSPO binding and blood CRP concentration or body mass index poses questions about the interactions between central and peripheral immune responses in the pathogenesis of depression., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Cerebrospinal fluid (CSF) plays an important role in solute clearance and maintenance of brain homeostasis. 11 C-Pittsburgh compound B (PiB) PET was recently proposed as a tool for detection of CSF clearance alterations in Alzheimer disease. The current study investigates the magnitude of 11 C-PiB PET signal in the lateral ventricles of an independent group of Alzheimer and mild cognitive impairment subjects. We have also evaluated multiple sclerosis as a model of disease with CSF clearance alterations without amyloid-β tissue accumulation. Methods: A set of 11 Alzheimer and 12 mild cognitive impairment subjects and a set of 20 multiple sclerosis subjects with matched controls underwent MRI and dynamic 11 C-PiB PET. Lateral ventricle regions of interest were generated manually from MRI data. PET data were analyzed using cerebellum or a supervised reference region for the Alzheimer and multiple sclerosis data sets, respectively. The magnitude of 11 C-PiB signal in the lateral ventricles was calculated as area under the curve from 35 to 80 min and SUV ratio (SUVR) from 50 to 70 min. Compartmental modeling analysis was performed on a separate data set containing 11 Alzheimer and matched control subjects; this analysis included an arterial input function, to further understand the kinetics of the lateral ventricular 11 C-PiB signal. Results: ANOVA revealed significant group differences in lateral ventricular SUVR across the Alzheimer, mild cognitive impairment, and healthy control groups ( P = 0.004). Pairwise comparisons revealed significantly lower lateral ventricular SUVR in Alzheimer subjects than in healthy controls ( P < 0.001) or mild cognitive impairment subjects ( P = 0.029). Lateral ventricular SUVR was significantly lower in multiple sclerosis subjects than in healthy controls ( P = 0.008). Compartmental modeling analysis revealed significantly lower uptake rates of 11 C-PiB signal from blood ( P = 0.005) and brain tissue ( P = 0.004) to the lateral ventricles and significantly lower 11 C-PiB signal clearance out of the lateral ventricles ( P = 0.002) in Alzheimer subjects than in healthy controls. Conclusion: These results indicate that dynamic 11 C-PiB PET can be used to observe pathologic changes in CSF dynamics. We have replicated previous work demonstrating CSF clearance deficits in Alzheimer disease associated with amyloid-β deposits and have extended the observations to include ventricular CSF clearance deficits in mild cognitive impairment and multiple sclerosis., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: To assess intensive care unit (ICU) complications, their management, and prognostic factors associated with outcomes in a cohort of patients with autoimmune encephalitis (AE)., Methods: This study was an observational multicenter registry of consecutively included patients diagnosed with AE requiring Neuro-ICU treatment between 2004 and 2016 from 18 tertiary hospitals. Logistic regression models explored the influence of complications, their management, and diagnostic findings on the dichotomized (0-3 vs 4-6) modified Rankin Scale score at hospital discharge., Results: Of 120 patients with AE (median age 43 years [interquartile range 24-62]; 70 females), 101 developed disorders of consciousness, 54 autonomic disturbances, 42 status epilepticus, and 39 severe sepsis. Sixty-eight patients were mechanically ventilated, 85 patients had detectable neuronal autoantibodies, and 35 patients were seronegative. Worse neurologic outcome at hospital discharge was associated with necessity of mechanical ventilation (sex- and age-adjusted OR 6.28; 95% CI, 2.71-15.61) tracheostomy (adjusted OR 6.26; 95% CI, 2.68-15.73), tumor (adjusted OR 3.73; 95% CI, 1.35-11.57), sepsis (adjusted OR 4.54; 95% CI, 1.99-10.43), or autonomic dysfunction (adjusted OR 2.91; 95% CI, 1.24-7.3). No significant association was observed with autoantibody type, inflammatory changes in CSF, or pathologic MRI., Conclusion: In patients with AE, mechanical ventilation, sepsis, and autonomic dysregulation appear to indicate longer or incomplete convalescence. Classic ICU complications better serve as prognostic markers than the individual subtype of AE. Increased awareness and effective management of these AE-related complications are warranted, and further prospective studies are needed to confirm our findings and to develop specific strategies for outcome improvement.