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Objective This retrospective cohort study analyzes risk factors for abnormal pre-pregnancy body mass index and abnormal gestational weight gain in twin pregnancies. Methods Data from 10 603/13 682 twin pregnancies were analyzed using uni- and multivariable logistic regression models to determine risk factors for abnormal body mass index and weight gain in pregnancy. Results Multiparity was associated with pre-existing obesity in twin pregnancies (aOR: 3.78, 95% CI: 2.71 – 5.27). Working in academic or leadership positions (aOR: 0.57, 95% CI: 0.45 – 0.72) and advanced maternal age (aOR: 0.96, 95% CI: 0.95 – 0.98) were negatively associated with maternal obesity. Advanced maternal age was associated with a lower risk for maternal underweight (aOR: 0.95, 95% CI: 0.92 – 0.99). Unexpectedly, advanced maternal age (aOR: 0.98, 95% CI: 0.96 – 0.99) and multiparity (aOR: 0.6, 95% CI: 0.41 – 0.88) were also associated with lower risks for high gestational weight gain. Pre-existing maternal underweight (aOR: 1.55, 95% CI: 1.07 – 2.24), overweight (aOR: 1.61, 95% CI: 1.39 – 1.86), obesity (aOR: 3.09, 95% CI: 2.62 – 3.65) and multiparity (aOR: 1.64, 95% CI: 1.23 – 2.18) were all associated with low weight gain. Women working as employees (aOR: 0.85, 95% CI: 0.73 – 0.98) or in academic or leadership positions were less likely to have a low gestational weight gain (aOR: 0.77, 95% CI: 0.64 – 0.93). Conclusion Risk factors for abnormal body mass index and gestational weight gain specified for twin pregnancies are relevant to identify pregnancies with increased risks for poor maternal or neonatal outcome and to improve their counselling. Only then, targeted interventional studies in twin pregnancies which are desperately needed can be performed.

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.

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.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.Pre-pregnancy body mass index ≥25 kg/mIn 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.

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 Knowledge The Social Status of Climate Change Knowledge > Sociology/Anthropology of Climate Knowledge The Social Status of Climate Change Knowledge > Knowledge and Practice, A traveler at the end of the world peeks beyond the limits of the Earth, reaching for the unknown skies. Wood Carving by Unknown Artist in Flammarion, C. (1888). L'atmosphère: Météorologie Populaire. Hachette., German University of Administrative Sciences, Speyer (Germany)

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 relationship between peripheral and central immunity and how these ultimately may cause depressed behaviour has been the focus of a number of imaging studies conducted with Positron Emission Tomography (PET). These studies aimed at testing the immune-mediated model of depression that proposes a direct effect of peripheral cytokines and immune cells on the brain to elicit a neuroinflammatory response via a leaky blood–brain barrier and ultimately depressive behaviour. However, studies conducted so far using PET radioligands targeting the neuroinflammatory marker 18 kDa translocator protein (TSPO) in patient cohorts with depression have demonstrated mild inflammatory brain status but no correlation between central and peripheral immunity. To gain a better insight into the relationship between heightened peripheral immunity and neuroinflammation, we estimated blood-to-brain and blood-to-CSF perfusion rates for two TSPO radiotracers collected in two separate studies, one large cross-sectional study of neuroinflammation in normal and depressed cohorts (N = 51 patients and N = 25 controls) and a second study where peripheral inflammation in N = 7 healthy controls was induced via subcutaneous injection of interferon (IFN)-α. In both studies we observed a consistent negative association between peripheral inflammation, measured with c-reactive protein P (CRP), and radiotracer perfusion into and from the brain parenchyma and CSF. Importantly, there was no association of this effect with the marker of BBB leakage S100β, that was unchanged. These results suggest a different model of peripheral-to-central immunity interaction whereas peripheral inflammation may cause a reduction in BBB permeability. This effect, on the long term, is likely to disrupt brain homeostasis and induce depressive behavioural symptoms.

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.

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 disease of the central nervous system.

Notions of the impending climate crisis have pushed a set of highly contested techno-scientific measures onto policy agendas around the world. Suggestions to deliberately alter, to engineer, the Earth’s climate have gained political currency in recent years not as a positive vision of techno-scientific innovation, but as a daunting measure of last resort. The controversial status of various so-called climate engineering proposals raises a simple, yet pressing question: How has it has come to this? And, more specifically, how did such contested measures earn their place on policy agendas, despite enormous scientific complexities and fierce political contestation? Global societal problems, such as climate change, financial crises, or pandemics have brought the political relevance of scientific expertise to the foreground. This book speaks to scholarship in sociology and science studies, seeking to illuminate the essential entanglements between efforts to understand and efforts to govern such problems. By giving climate engineering a life of its own and following its dynamic trajectory as a contested object of expert work, this book sheds light on the reflexive and historically contingent interplay of science and politics as two distinct, yet increasingly interdependent, realms of society.

BackgroundRecent 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.Methods51 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.ResultsWe found a significantly greater CP volume in depressed subjects compared to HCs (t(76) = +2.17) that was positively correlated with [11C]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 [11C]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.ConclusionThis 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.

Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.

Purpose This technical note seeks to act as a practical guide for implementing a supervised clustering algorithm (SVCA) reference region approach and to explain the main strengths and limitations of the technique in the context of 18-kilodalton translocator protein (TSPO) positron emission tomography (PET) studies in experimental medicine. Background TSPO PET is the most widely used imaging technique for studying neuroinflammation in vivo in humans. Quantifying neuroinflammation with PET can be a challenging and invasive procedure, especially in frail patients, because it often requires blood sampling from an arterial catheter. A widely used alternative to arterial sampling is SVCA, which identifies the voxels with minimal specific binding in the PET images, thus extracting a pseudo-reference region for non-invasive quantification. Unlike other reference region approaches, SVCA does not require specification of an anatomical reference region a priori, which alleviates the limitation of TSPO contamination in anatomically-defined reference regions in individuals with underlying inflammatory processes. Furthermore, SVCA can be applied to any TSPO PET tracer across different neurological and neuropsychiatric conditions, providing noninvasivequantification of TSPO expression. Methods We provide an overview of the development of SVCA as well as step-by-step instructions for implementing SVCA with suggestions for specific settings. We review the literature on SVCAapplications using first- and second- generation TSPO PET tracers and discuss potential clinically relevant limitations and applications. Conclusions The correct implementation of SVCA can provide robust and reproducible estimates of brain TSPO expression. This review encourages the standardisation of SVCA methodology in TSPO PET analysis, ultimately aiming to improve replicability and comparability across study sites.

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 11C-PK11195 PET and peripheral blood immune marker characterization. Depressed subjects were divided into high CRP (>3 mg/L; n = 20) and low CRP (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.

The relationship between peripheral and central immunity and how these ultimately may cause depressed behaviour has been the focus of a number of imaging studies conducted with Positron Emission Tomography (PET). These studies aimed at testing the immune-mediated model of depression that proposes a direct effect of peripheral cytokines and immune cells on the brain to elicit a neuroinflammatory response via a leaky blood-brain barrier and ultimately depressive behaviour. However, studies conducted so far using PET radioligands targeting the neuroinflammatory marker 18 kDa translocator protein (TSPO) in patient cohorts with depression have demonstrated mild inflammatory brain status but no correlation between central and peripheral immunity.To gain a better insight into the relationship between heightened peripheral immunity and neuroinflammation, we estimated blood-to-brain and blood-to-CSF perfusion rates for two TSPO radiotracers collected in two separate studies, one large cross-sectional study of neuroinflammation in normal and depressed cohorts and a second study where peripheral inflammation in healthy controls was induced via subcutaneous injection of interferon (IFN)-α. In both studies we observed a consistent negative association between peripheral inflammation, measured with c-reactive protein P (CRP), and radiotracer perfusion into and from the brain parenchyma and CSF. Importantly, there was no association of this effect with the marker of BBB leakage S100β, that was unchanged, but there was an association between the reduction of tracer perfusion in volunteers injected with interferon (IFN)-α and VEGF, a potent vascular permeability factor.These results support a different model of peripheral-to-central immunity interaction whereas peripheral inflammation causes a “stiffening” of the healthy BBB with consequent reduction of small molecule trafficking to and from the blood into the brain and CSF. This effect, on the long term, is likely to disrupt brain homeostasis and induce depressive behavioural symptoms. Moreover, given the molecular similarity between the TSPO ligands and antidepressant, this phenomenon may underlie treatment resistance in depressive cohorts with heightened peripheral status.

BACKGROUNDImmune mechanisms have been implicated in the pathogenesis of depression, and translocator-protein (TSPO) targeted positron emission tomography (PET) has been used to assess neuroinflammation in major depressive disorder. We aimed to: (i) test the prior hypothesis of significant case-control differences in TSPO binding in anterior cingulate (ACC), prefrontal (PFC) and insular (INS) cortical regions; and (ii) explore the relationship between cerebral TSPO binding and peripheral blood concentration of C-reactive protein (CRP).METHODS51 depressed cases with Hamilton Depression Rating Scale score > 13 (median 17; IQR 16-22) and 25 healthy matched controls underwent dynamic brain 11C-PK11195 PET and peripheral blood immune marker characterisation. Depressed cases were divided into high CRP (>3mg/L;N=20) and low CRP (RESULTSAcross the three regions, TSPO binding was significantly increased in cases vs controls (; F(1,71)=6.97, P=0.01). which was not influenced by differences in body mass index (BMI). The case-control difference was greatest in ACC (d=0.49; t(74)=2.00, .P=0.03) and not significant in PFC or INS (d=0.27; d=0.36). Following CRP stratification, significantly higher TSPO binding was observed in low CRP depression compared to controls (d=0.53; t(54)=1.96, P=0.03). These effect sizes are comparable to prior MDD case-control TSPO PET data. No significant correlations were observed between TSPO and CRP measures.CONCLUSIONSConsistent with previous findings, there is a modest increase in TSPO binding in depressed cases compared to healthy controls. The lack of a significant correlation between brain TSPO binding and blood CRP concentration or BMI poses questions about the interactions between central and peripheral immune responses in the pathogenesis of depression.

This contribution explores the political dimension of TechnoScienceSocieties. We assume that technoscientific knowledge production as well as the governance of technoscience is guided by historically contingent rationales. Such rationales have been conceptualized as „sociotechnical imaginaries“ by STS scholars. However, these imaginaries often remain vague and implicit and it is unclear how they are entangled with mundane STI policies. Against this background, our hypothesis is that one way for sociotechnical imaginaries to become politically explicit is the popular reference to “grand challenges.” To illustrate this, we trace the trajectories of two technoscientific discourses, both of which evolve around specific global problems: energy security and climate engineering. By means of historical discourse analysis, we follow their origin and transformations, as well as their proposed response measures through history and through various social and cultural contexts. The case studies illustrate how historical actors translate (implicit) visions encoded in sociotechnical imaginaries into (explicit) problems framed as “grand challenges.” The contribution concludes by reflecting on how an analysis of “grand challenges” can contribute to a refinement of the sociotechnical imaginaries framework.

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.

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.

This contribution explores the role of quantified scientific expertise for U.S. geoengineering politics. Drawing on empirical evidence from federal proceedings, it assesses how climate measures, models, targets, and thresholds have shaped the trajectory of geoengineering within U.S. climate policy between 1990 and 2015. The analysis distinguishes three stages, in which this “career” of geoengineering has been advanced, each pointing to distinct capacities of quantified expertise: from contesting the “discernible human influence” on the climate, to quantifying the size of this challenge, all the way to devising an “emergency tool”. Going beyond the specific case of geoengineering, this contribution thus illuminates how context dependent not only our understanding of societal problems is, but also our comprehension of the kinds of responses we deem legitimate. Specifically, it demonstrates how numbers “work” in communicating global challenges, and how they guide the choices we make in seeking to address them.

Cerebrospinal fluid (CSF) plays an important role in the clearance of solutes and maintenance of brain homeostasis. 11C-PiB PET was recently proposed as a tool for detection of CSF clearance alterations in Alzheimer’s disease. The current study seeks to investigate the magnitude of 11C-PiB PET signal in the lateral ventricles of an independent group of Alzheimer’s and mild cognitive impairment subjects. We have also evaluated multiple sclerosis as a model of disease with CSF clearance alterations without amyloid-beta tissue accumulation.MethodsA set of Alzheimer’s and mild cognitive impairment subjects and a set of multiple sclerosis subjects with matched healthy controls underwent MRI and dynamic 11C-PiB PET. Manual lateral ventricle regions of interest were generated from MRI data. PET data was analysed using a simplified reference tissue model with cerebellum or a supervised reference region, for the Alzheimer’s and multiple sclerosis datasets, respectively. Magnitude of 11C-PiB signal in the lateral ventricles was calculated as area under curve from 35 to 80 minutes and standard uptake value ratio (SUVR) from 50 to 70 minutes. Compartmental modelling analysis was performed on a separate dataset containing Alzheimer’s and matched healthy control data with an arterial input function to further understand the kinetics of the lateral ventricular 11C-PiB signal.ResultsAnalysis of variance revealed significant group differences in lateral ventricular SUVR across the Alzheimer’s, mild cognitive impairment, and healthy control groups (p=0.004). Additional pairwise comparisons revealed significantly lower lateral ventricular SUVR in Alzheimer’s compared to healthy controls (p11C-PiB signal from blood (p=0.005) and brain tissue (p=0.004) to the lateral ventricles in Alzheimer’s compared to healthy controls. This analysis also revealed significantly lower clearance of 11C-PiB signal out of the lateral ventricles in Alzheimer’s compared to healthy controls (p=0.002).ConclusionOverall, these results indicate that dynamic 11C-PiB PET can be used to observe pathological changes in cerebrospinal fluid dynamics and that cerebrospinal fluid-mediated clearance is reduced in Alzheimer’s disease and multiple sclerosis compared to healthy controls.

Ever since the Enlightenment, „science has been associated with an ideal of speaking truth to power“ (T. M. Porter 2006, p. 1288). Even more so today, in the face of ‘Grand Societal Challenges’ and ‘Wicked Problems’, scientific expertise seems to be an increasingly essential asset to modern politics. But in spite of extensive social scientific research on the matter, the question remains: How should we conceptualize this ‘speaking truth to power’? The paper contributes to tackling precisely this research question. A conceptual framework is outlined, which explores approaching the question via the organizational interface of politics and its knowledgerelevant environment. By focusing on the specific instances and diverse organizational forms that process this science-politics interface, the article aims at contributing to substantiate and understand the genuinely political relevance of scientific expertise. Keywords: ‘Scientization’, scientific expertise, political decision-making, science-politics interface, organizational analysis ----- Organisationen als Schnittstelle zwischen Politik und Wissenschaft. Vorschlag eines analytischen Rahmenprogramms Zusammenfassung Spatestens seit der Aufklarung des 18. Jahrhunderts wird der Wissenschaft das Ideal von „speaking truth to power“ (Porter 2006, p.1288) zugeschrieben. Eine Assoziation, welche gerade unter dem gegenwartigen Eindruck von ‚Grand Societal Challenges’ und ‚Wicked Problems’ fur die moderne Politik, die scheinbar mehr denn je auf wissenschaftliche Expertise angewiesen ist, erneut an Aktualitat gewinnt. Doch trotz umfassender sozialwissenschaftlicher Auseinandersetzung mit dem Thema bleibt die Frage nach einer aufschlussreichen Konzeptualisierung dieses ‚speaking truth to power’ soziologisch weiterhin umstritten. Der vorliegende Artikel mochte zur Beantwortung eben jener Frage beitragen. Dazu wird ein analytisches Rahmenprogramms skizziert, welches die Organisationen an der Schnittstelle von Politik und ihrer wissensrelevanten Umwelt in den Blick nimmt: Uber das Studium der konkreten Instanzen und spezifischen organisationalen Konstellationen, welche die Kopplung von Wissenschaft und Politik steuern, mochte der Artikel zum Verstandnis der genuin politischen Bedeutung wissenschaftlicher Expertise beitragen. Schlagworte: Verwissenschaftlichung, wissenschaftliche Expertise, politische Entscheidungsprozesse, Organisationsanalyse ----- Bibliographie: Schubert, Julia: The Organizational Interface of Science and Politics, dms, 1-2016, S. 51-64. https://doi.org/10.3224/dms.v9i1.23640

Spontaneous plastome mutants have been used as a research tool since the beginning of genetics. However, technical restrictions have severely limited their contributions to research in physiology and molecular biology. Here, we used full plastome sequencing to systematically characterize a collection of 51 spontaneous chloroplast mutants in Oenothera (evening primrose). Most mutants carry only a single mutation. Unexpectedly, the vast majority of mutations do not represent single nucleotide polymorphisms but are insertions/deletions originating from DNA replication slippage events. Only very few mutations appear to be caused by imprecise double-strand break repair, nucleotide misincorporation during replication, or incorrect nucleotide excision repair following oxidative damage. U-turn inversions were not detected. Replication slippage is induced at repetitive sequences that can be very small and tend to have high A/T content. Interestingly, the mutations are not distributed randomly in the genome. The underrepresentation of mutations caused by faulty double-strand break repair might explain the high structural conservation of seed plant plastomes throughout evolution. In addition to providing a fully characterized mutant collection for future research on plastid genetics, gene expression, and photosynthesis, our work identified the spectrum of spontaneous mutations in plastids and reveals that this spectrum is very different from that in the nucleus.

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.

ObjectiveTo assess intensive care unit (ICU) complications, their management, and prognostic factors associated with outcomes in a cohort of patients with autoimmune encephalitis (AE).MethodsThis 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.ResultsOf 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.ConclusionIn 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.

This appendix supplements the following article: 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.

Die Diagnosen von Postdemokratie und Verwissenschaftlichung der Politik treffen sich in ihrer Krisendiagnose der modernen Demokratie: Politische Entscheidungen wurden zunehmend von Experten und Wissenschaftlern oder gar von unpersonlichen „decision technologies“ (Porter, 2006) getroffen. Der vorliegende Beitrag untersucht die Darstellung politischer Entscheidungen in drei deutschen Printmedien zwischen 1946 und 2011 und stellt die Frage, ob diese in einem zunehmend verwissenschaftlichten Kontext prasentiert werden. Das Konzept einer Verwissenschaftlichung wird dabei – in Auseinandersetzung mit zentralen Diskursen der Wissensgesellschaft – in drei Dimensionen unterteilt: „akademische („klassische“) Wissenschaft“, „Expertise“ sowie „Quantifizierung und Prazision“. Es kann gezeigt werden, dass die drei Dimensionen unterschiedliche Kontexte des Verweisens auf Wissenschaft bezeichnen. Die Hypothese einer zunehmenden Verwissenschaftlichung politischer Entscheidungen muss jedoch abgelehnt werden: Weder zeigt sich eine eindeutig zu- oder abnehmende Tendenz, noch lassen sich signifikante Hoch- oder Tiefpunkte der allgemeinen Verwissenschaftlichung beobachten. Andererseits kann ein grundsatzlicher Ruckgang der massenmedialen Thematisierung politischen Entscheidens verzeichnet werden – es wird also ganz allgemein zunehmend weniger uber politische Entscheidungen gesprochen. Diese Ergebnisse werden in vier Fallstudien genauer uberpruft.

Putative XyG xylosyltransferases from Tropaeolum majus (nasturtium) and Solanum lycopersicum (tomato) homologous to characterized Arabidopsis genes were identified and shown to functionally complement Arabidopsis mutants lacking xyloglucan demonstrating they represent xyloglucan xylosyltransferases. Xyloglucan is a major hemicellulose in the plant cell wall and is important for the structural organization of the wall. The fine structure of xyloglucan can vary dependent on plant species and tissue type. Most vascular seed-bearing plants including Arabidopsis thaliana and nasturtium (Tropaeolum majus) have a xyloglucan structure, in which three out of four backbone glucosyl-residues are substituted with xylosyl-residues. In contrast, the xyloglucan found in plants of the Solanaceae family, which includes tomato (Solanum lycopersicum), is typically less xylosylated with only two of the four backbone glucosyl-residues substituted with xylosyl-residues. To investigate the genetics of xyloglucan xylosylation, candidate xyloglucan xylosyltransferase genes (XXTs) homologous to known A. thaliana XXTs were cloned from nasturtium and tomato. These candidate XXTs were expressed in the A. thaliana xxt1/2 double and xxt1/2/5 triple mutant, whose walls lack detectable xyloglucan. Expression of the orthologs of XXT5 resulted in no detectable xyloglucan in the transgenic A. thaliana plants, consistent with a lack of xyloglucan in the A. thaliana xxt1/2 double mutant. However, transformation of both the tomato and nasturtium orthologs of AtXXT1 and AtXXT2 resulted in the production of xyloglucan with a xylosylation pattern similar to wild type A. thaliana indicating that both SlXXT2 and TmXXT2 likely have xylosyltransferase activity. As the expression of the SlXXT2 did not result in xyloglucan with a decreased xylosylation frequency found in tomato, this gene is not responsible for the unique xylosylation pattern found in the solanaceous plants.

In glioblastoma multiforme (GBM), a tumor still characterized by dismal prognosis, recent research focuses on novel-targeted compounds, in addition to standard temozolomide (TMZ) chemotherapy. One of these emerging compounds is cilengitide (CGT), which by binding to integrins (i.e., αvβ3 and αvβ5) may inhibit angiogenesis and also is directly cytotoxic to tumor cells by interfering with intracellular signaling pathways. A total of ten patient-derived ultra-low passage GBM cell lines were treated with increasing doses of CGT, TMZ, and a combination of both substances. Inhibitory concentrations of 50 % (IC50) were determined for the single agents and as a combination. Cell lines were stratified according to MGMT promoter methylation. The expression of relevant integrins was assessed by flow cytometry. In monotherapy, all GBM cell lines showed higher sensitivity to CGT than to TMZ, as determined by IC50 values in relation to clinically relevant patient plasma levels. MGMT promoter methylation correlated with a significantly higher TMZ response, but tended to be associated with a lower CGT response. Response to CGT was not correlated with cell surface integrin expression as measured by flow cytometry. Finally, addition of CGT to TMZ enhanced growth inhibition, but only in those cell lines with a methylated MGMT promoter. As suggested by this analysis, patients with MGMT promoter-methylated GBM may benefit from addition of CGT to the standard TMZ treatment, while patients with MGMT promoter-unmethylated GBM may better respond to CGT monotherapy.

e13053 Background: Glioblastoma multiforma (GBM) still has a very poor prognosis even with today’s multimodal combination therapy of resection followed by radio-chemotherapy with temozolomide. Both new molecular inhibitors and immunotherapy may represent future therapeutical tools but due to the variability of the molecular composition in individual GBM, they probably depend on better response prediction. Methods: Based on a close cooperation and logistics between surgery, pathology, laboratory researchers and animal care facilities, we established and analysed cell lines of about 30 primary brain tumors, most of them GBM. Tumors and cell lines were characterised by morphology, growth behaviour, numerous extra- and intracellular antigens, and particularly regarding molecular features. Further, tumors were established in a subcutaneous xenograft mouse model, and growth characteristics were described. These in vitro and in vivo models represent an ideal tool for response analysis of single agent or combined treatment in early cell passages in order to predict response. Besides, relevant antigens and possible shifts of antigen-presentation in tumors can be assessed. Numerous analyses using established and new antitumor compounds – e.g. the integrin inhibitor cilengitide – were performed. Results: We found that although the specific integrin expression is individually different in the tumors analysed, cilengitide sensitivity was similar in most. Addition of temozolomide led to additional, yet not over-additive cytotoxicity. In our panel of GBM specimens we found a very heterogenous pattern of molecular alterations, going along with variations of drug sensitivity. Conclusions: This indicates that, in the future field of individualized approaches, such models are required, in order to enable future strategies to predict the efficacy of immunological, small molecular, biological-based, cytotoxic or other therapeutic strategies. The project was supported by the Förderkreis für krebskranke Kinder Rostock e.V., by a Mecklenburg-Vorpommern graduate scholarship, and by a cooperation with Merck-Serono Research and Development (gift of drug).