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Measurement of the e+e−→π+π− cross section between 600 and 900 MeV using initial state radiation
(2016)
We extract the e+e− →π+π− cross section in the energy range between 600 and 900 MeV, exploiting the method of initial state radiation. A data set with an integrated luminosity of 2.93 fb−1 taken at a center-of-mass energy of 3.773 GeV with the BESIII detector at the BEPCII collider is used. The cross section is measured with a systematic uncertainty of 0.9%. We extract the pion form factor |Fπ|2 as well as the contribution of the measured cross section to the leading-order hadronic vacuum polarization contribution to (g−2)μ. We find this value to be aππ,LO μ (600–900 MeV) = (368.2 ±2.5stat±3.3sys) ·10−10, which is between the corresponding values using the BaBar or KLOE data.
By analyzing the large-angle Bhabha scattering events e+e− → (γ)e+e− and diphoton events e+e− → (γ)γγ for the data sets collected at center-of-mass (c.m.) energies between 2.2324 and 4.5900 GeV (131 energy points in total) with the upgraded Beijing Spectrometer (BESIII) at the Beijing Electron-Positron Collider (BEPCII), the integrated luminosities have been measured at the different c.m. energies, individually. The results are important inputs for the R value and J/ψ resonance parameter measurements.
Mitigating climate change necessitates global cooperation, yet global data on individuals’ willingness to act remain scarce. In this study, we conducted a representative survey across 125 countries, interviewing nearly 130,000 individuals. Our findings reveal widespread support for climate action. Notably, 69% of the global population expresses a willingness to contribute 1% of their personal income, 86% endorse pro-climate social norms and 89% demand intensified political action. Countries facing heightened vulnerability to climate change show a particularly high willingness to contribute. Despite these encouraging statistics, we document that the world is in a state of pluralistic ignorance, wherein individuals around the globe systematically underestimate the willingness of their fellow citizens to act. This perception gap, combined with individuals showing conditionally cooperative behaviour, poses challenges to further climate action. Therefore, raising awareness about the broad global support for climate action becomes critically important in promoting a unified response to climate change.
It is widely acknowledged that biodiversity change is affecting human well-being by altering the supply of Nature's Contributions to People (NCP). Nevertheless, the role of individual species in this relationship remains obscure. In this article, we present a framework that combines the cascade model from ecosystem services research with network theory from community ecology. This allows us to quantitatively link NCP demanded by people to the networks of interacting species that underpin them. We show that this “network cascade” framework can reveal the number, identity and importance of the individual species that drive NCP and of the environmental conditions that support them. This information is highly valuable in demonstrating the importance of biodiversity in supporting human well-being and can help inform the management of biodiversity in social-ecological systems.
Coercion or privatization? Crisis and planned economies in the debates of the early Frankfurt School
(2023)
The 1930s–1940s underwent profound structural economic and political turmoil following the collapse of the nineteenth century liberal market economies. The intellectual debates of the time were dominated by the question of whether Marx’s theory of the tendency of rate of profit to fall was true, or what consequence could be imagined in the survival of capitalist societies. Placed in the middle of such debates was also the reorganization of national productions into war economies. By means of reconstructive analysis, the paper provides a critical overview of the debates that took place within the circle of the Frankfurt School during those years. It also advances an interpretive thesis suggesting that remedies to capitalist crises of the time turned state powers into privatized, illiberal coercive entities. Coercion and privatization reinforced each other. This general tendency is well illustrated by the famous Pollock-Neumann debate. These intellectuals expressed views not only intended to shed light on the historical period of time, but also to formulate long-term considerations on the authoritarian trends embedded in our contemporary democracies. Through historical reconstruction, the paper’s aim is to identify a long-term structural thread of transformation starting from the transformation of the German economy in 1930s and touching upon post Second World War problems of states’ restructuring along privatization/coercion divides.
Detailed feedback on exercises helps learners become proficient but is time-consuming for educators and, thus, hardly scalable. This manuscript evaluates how well Generative Artificial Intelligence (AI) provides automated feedback on complex multimodal exercises requiring coding, statistics, and economic reasoning. Besides providing this technology through an easily accessible web application, this article evaluates the technology’s performance by comparing the quantitative feedback (i.e., points achieved) from Generative AI models with human expert feedback for 4,349 solutions to marketing analytics exercises. The results show that automated feedback produced by Generative AI (GPT-4) provides almost unbiased evaluations while correlating highly with (r = 0.94) and deviating only 6 % from human evaluations. GPT-4 performs best among seven Generative AI models, albeit at the highest cost. Comparing the models’ performance with costs shows that GPT-4, Mistral Large, Claude 3 Opus, and Gemini 1.0 Pro dominate three other Generative AI models (Claude 3 Sonnet, GPT-3.5, and Gemini 1.5 Pro). Expert assessment of the qualitative feedback (i.e., the AI’s textual response) indicates that it is mostly correct, sufficient, and appropriate for learners. A survey of marketing analytics learners shows that they highly recommend the app and its Generative AI feedback. An advantage of the app is its subject-agnosticism—it does not require any subject- or exercise-specific training. Thus, it is immediately usable for new exercises in marketing analytics and other subjects.
New U–Pb ages of detrital and igneous zircons of the Uppermost Unit of Crete shed light on its provenance and on Eohellenic to Eoalpine imprints in the eastern Mediterranean. The detrital zircons of all nappes show Variscan ages and are characterized by a Minoan-type age spectrum, which is typical for the NE margin of Gondwana. Parts of the metasedimentary rocks are unexpectedly young. Their detrital zircon ages continue via the Permian until the Late Triassic, Middle Jurassic and Early Cretaceous. The high-grade metamorphic rocks of the Asterousia crystalline complex are likely equivalents of the low-grade metamorphic trench and fore-arc deposits of the Vatos nappe pointing to Late Cretaceous slab roll back. The presence of both late Permian detrital zircons and Late Cretaceous arc-type granitoids suggest that the Uppermost Unit of Crete is derived from the late Permian/Late Cretaceous magmatic belt situated north of the Sava–Vardar–Izmir–Ankara Suture in the Strandja–Rhodope area. To achieve their recent position on Crete, the nappes had to travel more than 500 km. The traveling path is well tracked by rocks of the Upper Cycladic Unit, which are similar to those of the Uppermost Unit of Crete. The large displacement of the Cretan nappes was controlled not only by nappe transport, but probably also by dextral strike–slip along the North Anatolian Fault Zone and related counterclockwise rotation of the Anatolian block since the Eocene.
Highlights
• Solidification and cooling of an intruded dyke or sill within the middle or shallow crust generate stresses of order 200 MPa, which relax on time scales of a few years to million years.
• Stresses may exceed the brittle strength forming tensile fractures.
• Combined with the pressure gradient within the over-pressurized felsic melts, this explains the migration of felsic contact melt into shrinkage cracks (Sederholm-type veins).
Abstract
Rapid emplacement of a mafic dyke or sill at mid-crustal depth heats and possibly melts the felsic wall rock followed by solidification. Associated volume changes generate stresses, possibly enforcing brittle failure and melt migration. We model the evolution of melting, solidification, temperature, and stress including visco-elastic relaxation in 1D - dykes or -sills using realistic rock rheologies of the Weschnitz pluton (Odenwald). For deep emplacement (Case 1, 15.3 km) extensive contact melting of the wall rock occurs, for shallow emplacement (Case 2, 10 km) it is negligible. The stresses are zero at high melt fractions, but increase during solidification and cooling: The intrusion orthogonal stress is always zero. The intrusion parallel stress σ‖ within the intrusion is tensile (O(200 MPa)). It relaxes on a time scale between a few years (Case 1) and 0.6 m.y. (Case 2). Within the wall rock σ‖ is compressive during heating, but becomes tensile under solidification and cooling. Wall rock stresses relax on a time scale of months to 100 years. A Deborah number is defined based on viscous to thermal relaxation allowing generalization of our results. Adding lithostatic stresses, the total stresses of Case 1 remain below the brittle strength, while for Case 2 they may exceed it. Adding the lithostatic pressure to the melt pressure, the effective stresses exceed the brittle strength and intrusion orthogonal tensile fractures are predicted. Combined with the pressure gradient within the over-pressurized felsic melts generated in the wall rock, this explains the migration of felsic contact melt into shrinkage cracks of the mafic sill in the Weschnitz pluton.
Highlights
• It is important to distinguish acute provoked seizures due to autoimmune encephalitis from chronic unprovoked seizures due to autoimmune-associated epilepsy.
• Currently it is hardly possible in an individual AIE/ALE/RE patient to separate acute provoked seizures from chronic unprovoked seizures due to limitations in determining seizure outcomes, unclear time courses, potential causal interactions between both seizure origins, compartmentalized immune-inflammation, and a lack of licensed drugs to reliably resolve immune-inflammation in the brain parenchyma.
• This makes it hard to decide when to terminate ASMs and to counsel the individual patient regarding driving abilities and other behavioral restrictions and recommendations.
• Studies are urgently needed to define clinical and paraclinical biomarkers in a hypothesis-free, data-driven approach reliably predicting (or not) the development of AAE and the cognitive and behavioral outcome in the due course of an individual patient´s disease.
• These studies should be experimentally validated in suitable animal models.
Abstract
The current International League Against Epilepsy (ILAE) definition and classification guidelines for the first time introduced the category of immune-mediated focal epilepsy in addition to structural, genetic, infectious, and metabolic aetiologies. Moreover, the ILAE Autoimmunity and Inflammation Taskforce recently provided a conceptual framework for the distinction between acute “provoked” seizures in the acute phase of autoimmune encephalitis from chronic “unprovoked” seizures due to autoimmune-associated epilepsy. The first category predominately applies to those autoimmune encephalitis patients with autoantibodies against cell surface neural antigens, in whom autoantibodies are assumed to exert a direct ictogenic effect without overt structural damage. These patients do not exhibit enduring predisposition to seizures after the “acute phase” encephalitis, and thus do not fulfil the definition of epilepsy. The second category applies to those autoimmune encephalitis patients with autoantibodies against intracellular neural antigens and Rasmussen's encephalitis, in whom T cells are assumed to cause epileptogenic effects through immune-inflammation and overt structural damage. These patients do exhibit enduring predisposition to seizures after the “acute phase” of encephalitis and thus fulfil the definition of epilepsy. AAE may result from both, ongoing brain autoimmunity and associated structural brain damage according to the current ILAE definition and classification guideline. We here discuss the shortcomings and defaults of this concept and suggest an unbiased translationally validated and data-driven approach to predict in an individual encephalitis patient the propensity to develop (or not) AAE and the cognitive and behavioural outcome.
Despite antagonizing attempts from the tobacco industry, passive inhalation of tobacco smoke is known to be cancerogenic and toxic to human health for decades. Nonetheless, millions of non-smoking adults and children are still victims of second-hand smoke. Accumulation of particulate matter (PM) in confined spaces such as the car are particularly harmful due to high concentrations. We here aimed to analyze the specific effects of ventilation conditions in the setting of a car. By the use of the measuring platform TAPaC (tobacco-associated particulate matter emissions inside a car cabin), 3R4F reference cigarettes, Marlboro red, and Marlboro gold were smoked in a car interior with a volume of 3.709 m3. Seven different ventilation conditions (C1–C7) were analyzed. Under C1, all windows were closed. Under C2–C7, the car ventilation was turned on power level 2/4 with the air directed towards the windshield. Only the passenger side window was opened, where an outer placed fan could create an airstream speed of 15.9–17.4 km/h at one meter distance to simulate a driving car. C2: Window 10 cm opened. C3: Window 10 cm opened with the fan turned on. C4: Window half-opened. C5: Window half-opened with the fan turned on. C6: Window fully opened. C7: Window fully opened with the fan turned on. Cigarettes were remotely smoked by an automatic environmental tobacco smoke emitter and a cigarette smoking device. Depending on the ventilation condition the cigarettes emitted different mean PM concentrations after 10 min under condition C1 (PM10: 1272–1697 µg/m3, PM2.5: 1253–1659 µg/m3, PM1: 964–1263 µg/m3) under C2, C4, and C6 (PM10: 68.7–196.2 µg/m3, PM2.5: 68.2–194.7 µg/m3, PM1: 66.1–183.8 µg/m3) C3, C5, and C7 (PM10: 73.7–139 µg/m3, PM2.5: 72–137.9 µg/m3, PM1:68.9–131.9 µg/m3). Vehicle ventilation is insufficient to protect passengers from toxic second-hand smoke completely. Brand-specific variations of tobacco ingredients and mixtures markedly influence PM emissions under ventilation conditions. The most efficient ventilation mode to reduce PM exposure was achieved by opening the passenger´s window 10 cm and turning the onboard ventilation on power level 2/4. In-vehicle smoking should be banned to preserve innocent risk groups (e.g., children) from harm.
Die Digitalisierung aller Lebensbereiche stellt die Bildungsarbeit in Schulen, Kirchgemeinden und in der Gedenkstättenpädagogik vor neue Herausforderungen. Der Artikel beschreibt vor diesem Hintergrund Digitalisierungsprojekte an der Goethe-Universität in Frankfurt am Main, die sich mit virtuellen Realitäten, ambivalenten Narrativen und fiktiven Entscheidungssituationen beschäftigen. Besondere Aufmerksamkeit erhalten dabei das Judentum und die bildungstheoretischen Anliegen einer Didaktik der Multiperspektivität.
Two new species of Perinereis with single bar-shaped paragnaths on area VI (Group 1) from the rocky shores of Mumbai, Maharashtra, India, are described with barely (Subgroup 1A) or largely (Subgroup 1B) expanded proximal region of dorsal ligule in posterior parapodia. Perinereis malabarensis sp. nov. can be distinguished from the morphologically similar 1B species P. euiini Park & Kim, 2017 by the paragnath count in area I, the laterally isolated paragnaths in area III, and the length of the dorsal cirrus and dorsal ligule. Additionally, P. misrai sp. nov. is more similar to 1A species P. falsovariegata Monro, 1933 and P. villalobosi Rioja, 1947, but differs by the paragnath count in areas III–V and VII–VIII, the isolated paragnaths in area III, and the number of rows in the anterior band of areas VII–VIII. The morphological characters of the current 44 species within Perinereis G1 are compared, and an identification key to the species belonging to this group is also provided.
The taxonomic status of recently described Isophya taxa from Serbia (Tettigoniidae, Phaneropterinae)
(2024)
During recent decades, increasing research of the taxonomy of the genus Isophya resulted in taxonomic descriptions of several new species. The delimitation of these species is mainly based on oscillographic song analysis of the male song in combination with morphological characters, such as the shape of male cerci, tegmina and ovipositor. In the present paper, we used an integrative taxonomic approach in order to resolve the status of four recently described Isophya taxa from Serbia. Based on our molecular and bioacoustic analyses, all analyzed taxa belong to a single species: Isophya modestior. The majority of the morphological characters used to differentiate the taxa showed strong intra- and interpopulational variability, proving that describing new species within the genus Isophya should not rely on morphological characters alone, but needs to consider bioacoustic analyses as the main tool and a larger series of specimens.
A collection of 1149 otoliths of the Ypresian and Ypresian–Lutetian transition (early Eocene) from 18 sites across five states in the eastern and southern regions of the USA was analyzed. In total, 33 otolith-based taxa are documented, of which 27 are identified at the species level. Nine of these are introduced as new species: “Conger” biaculeatus sp. nov., Bauzaia gibbosa sp. nov., Ampheristus brevicaudatus sp. nov., Symmetrosulcus virginicus sp. nov., Neobythites longesulcatus sp. nov., “Neobythites” pamunkeyensis sp. nov., “Neobythites” stringeri sp. nov., Waitakia dorsogibbosa sp. nov., and “Haemulon” ypresiensis sp. nov. The assemblages are distinct when compared to their younger Eocene counterparts in America. This distinction is primarily characterized by the high proportion of the newly introduced species or exclusive Ypresian species. Additionally, we highlight the presence of 10 amphi-Atlantic species originally described in European deposits. Significantly, the composition of the otolith collection supports the interpretation of a shallow-water environment for the sampled sites during the Ypresian. This ecological setting appears to persist into the subsequent middle and late Eocene within the same geographic region.
Sparse sensor networks for Lamb wave-based structural health monitoring (SHM) can detect defects in plate-like structures. However, the limited number of sensor positions provides little information to characterize the unknown scatterer. This can be achieved by full wavefield analysis e.g. using Laser Doppler vibrometry measurements.
This paper proposes deconvolution processing that enhances the acoustic wavefield interpretation by increasing the temporal resolution of the underlying ultrasound signals. Applying this preprocessor to the whole wavefield allows improved non-destructive assessment of the defect. This approach is verified experimentally through a case study on an isotropic aluminum plate with four cracks.
The article presents the results of numerical and experimental investigations of guided wave propagation in aluminum plates with variable thickness. The shapes of plate surfaces have been specially designed and manufactured using a CNC milling machine. The shapes of the plates were defined by sinusoidal functions varying in phase shift, which forced the changes in thickness variability alongside the propagation path. The main aim of the study is to analyze the wave propagation characteristics caused by non-uniform thickness. In the first step, the influence of thickness variability on the time course of propagating waves has been analyzed theoretically. The study proves that the wave propagation signals can be determined based on knowledge about the statistical description of the specimen geometry. The histograms of thickness distribution together with the a priori knowledge of the dispersion curves were used to develop an iterative procedure assuming that the signal from the previous step becomes the excitation in the next step. Such an approach allowed for taking into account the complex geometry of the plate and rejecting the assumption about the constant average thickness alongside the propagation path. In consequence, it was possible to predict correctly the signal time course, as well as the time of flight and number of propagating wave modes in specimens with variable thickness. It is demonstrated that theoretical signals predicted in this way coincide well with numerical and experimental results. Moreover, the novel procedure allowed for the correct prediction of the occurrence of higher-order modes.
The topic of the article is the status of translation and homophony in philosophy, psychoanalysis and philology. The article focuses on the question of how translation is carried out using the basic principle of equivalence of meaning by homophony and what effects this can produce. The analysis of two case studies by Freud and Lacan shows that homophonic transfer from one language to another can be extremely productive for the subjective traversal of a phantasm. It is then shown that this is not, however, of purely subjective interest. Werner Hamacher has sketched the future of philology starting from such homophonic translations; Lacan has tried to advance to another theory of language through homophonic formations.
Die TPTZ-Citrat-Methode für die Eisenbestimmung im Serum bzw. Plasma zeichnet sich durch verschiedene Vorteile gegenüber anderen handelsüblichen Methoden aus.
1. Der Eisennachweis wird nur zu 2% durch Kupfer falsch-positiv gestört.
2. Die Farbreaktion erfolgt in Citratpuffer bei einem pH von 2,1 bis 2,5. Dieses Milieu ist günstig für die Freisetzung von Eisen aus der Transferrinbindung und gleichzeitig optimal für die Farbentwicklung. Es verhindert in der Regel Proteinpräzipitation, so daß ohne Enteiweißung gemessen werden kann. Die Freisetzung von Eisen aus Hämoglobin wird minimiert. Die Automation dieses Eisentests ist unproblematisch.
3. Die TPTZ-Citrat-Methode ist kostengünstig im Vergleich zu handelsüblichen Tests. Auf Reagenzienbasis reduziert sich der Preis pro Analyse auf 1/4 bis 1/10.
Insgesamt 311 Stämme gramnegativer harnwegspathogener Enterobacteriaceen und Nonfermenter, davon 200 Isolate aus frischem Urin der täglichen Routine und 111 ausgewählte, bezüglich ihrer Identifikation problematische Keime aus der Stammsammlung des Zentrums der Hygiene, Frankfurt/Main, wurden mit den Systemen RAS-ID-Gramne9, und API 20 E bzw. NE, vergleichend getestet. Das RAS~ID-Gramne9-System benutzt 10 biochemische Reaktionen zur Identifizierung gramnegativer Bakterien sowie 10 Chemotherapeutika zur Resistenzbestimmung. Von den 200 Routinestämmen zeigten 196 (98%), von den 111 Stämmen aus der Stammsammlung 98 (88,3 %) Übereinstimmung. Die gute Übereinstimmung und die schnelle und einfache Handhabung läßt das RAS-ID-Gramne9-System für die Identifizierung harnwegs-pathogener Routinekeime als kostengünstige Alternative zu anderen aufwendigeren Identifizierungssystemen erscheinen.
Das Virus der Frühsommermeningoenzephalitis (FSME) und Borrelia burgdorferi als Erreger der Lyme-Borreliose sind die klinischbedeutsamsten durch Zecken übertragenen Infektionserreger in Europa. Der vorliegende Fall beschreibt eine serologisch gesicherte. Doppelinfektion mit dem FSME-Virus und Borellia burgdorferi bei einer 69jährigen deutschen Patientin nach einem Zeckenstich in einem österreichischen Endemiegebiet. Klinisch bestand zum Zeitpunkt der Krankenhausaufnahme eine ausgeprägte Somnolenz und ein hochgradiges Doppelbildsehen. Ein passive Immunisierung gegen FSME war postexpositionell erfolgt, konnte eine Infektion jedoch nicht verhindern. Eine Doppelinfektion durch beide Erreger wurde durch den serologischen Nachweis von spezifischen IgG und IgM Antikörpern gegen das FSME-Virus und im weiteren Verlauf auch gegen Borrelia burgdorferi im ELISA beziehungsweise im rekombinanten Immunoblot gesichert. Obwohl Doppelinfektionen durch die beiden genannten Erregerselten sind, sollten sie bei zeckenübertragenen Erkrankungen mit untypischem Verlauf in der Differentialdiagnose berücksichtigt werden.
Im vorliegenden Fall wird von einer Fehldiagnose auf der Grundlage eines falsch-reaktiven Anti-HCV-Tests und eines falsch-reaktiven HCV-Nukleinsäureamplifikationstests (NAT) berichtet, die bei einem 58-jährigen chirurgischen Oberarzt im Rahmen einer arbeitsmedizinischen Vorsorgeuntersuchung im krankenhauseigenen Labor gestellt wurde und zu einem knapp zweimonatigen Berufsverbot führte. Basis dieser Fehldiagnose war ein wiederholt schwach reaktiver HCV-Antikörper-ELISA, der mit einem Nukleinsäureamplifikationstest, der ebenfalls schwach positiv ausfiel, überprüft wurde. Ein Antikörperbestätigungs- bzw. Ergänzungstest (Immunoblot) wurde nicht durchgeführt. Die Fehldiagnose ist jedoch nicht durch einen Testfehler, sondern durch ein Missverständnis entstanden, indem beim Kliniker zwei Laborindizien zu einem Beweis aufsummiert wurden.
Die steigende Zahl von Pilzinfektionen, die Entwicklung und Einführung neuer anti-mykotischer Substanzen sowie die Möglichkeit der Resistenzentwicklung unter Therapie mit Antimykotikahaben in der Vergangenheit zu einem ständig wachsenden Bedarf an standardisierten Verfahren zur Empfindlichkeitstestung von pathogenen Pilzen geführt. Hierbei entstand unter anderem eine Vielzahl kommerzieller Testverfahren, bei denen mit Hilfe vorgefertigter Testkits eine einfache und schnelle Durchführung der Empfindlichkeitsprüfung erzielt werden soll. Eine dieser Methoden, welche in manchen Laboratorien in Deutschland angewendet wird, ist das so genannte LD 2Ring-Verfahren, welches auf dem Prinzip der Agardiffusion beruht unter Verwendung vorgefertigter, antimy-kotika-beschichteter Papierringe. In der vorliegenden Arbeit wird dieses Verfahren auf seine Reproduzierbarkeit bei der Testung von zehn Qualitätskontrollstämmen hin überprüft. Die Ergebnisse zeigen eine starke Schwankungsbreite und somit eine schlechte Reproduzierbarkeit, so dass dieses Verfahren zwar für die Bearbeitung von wissenschaftlichen Fragestellungen, nicht jedoch für die Routinetestung als geeignet angesehen werden kann. Des Weiteren erfolgte eine Untersuchung auf das Vor-liegen eines so genannten "minor error", man erhält für einen sensiblen Stamm das Ergebnis "resistent", "major error", man erhält für einen intermediären Stamm das Ergebnis "sensibel", und "very major error", man erhaält für einen resistenten Stamm das Ergebnis "sensibel". Hierbei kam es in 16,25% der untersuchten Fälle zum Vorliegen eines "minor errors". Ein "major error" wurde nicht beobachtet
Background: Novel treatments are needed to control refractory status epilepticus (SE). This study aimed to assess the potential effectiveness of fenfluramine (FFA) as an acute treatment option for SE. We present a summary of clinical cases where oral FFA was used in SE.
Methods: A case of an adult patient with Lennox–Gastaut syndrome (LGS) who was treated with FFA due to refractory SE is presented in detail. To identify studies that evaluated the use of FFA in SE, we performed a systematic literature search.
Results: Four case reports on the acute treatment with FFA of SE in children and adults with Dravet syndrome (DS) and LGS were available. We report in detail a 30-year-old woman with LGS of structural etiology, who presented with generalized tonic and dialeptic seizures manifesting at high frequencies without a return to clinical baseline constituting the diagnosis of SE. Treatment with anti-seizure medications up to lacosamide 600 mg/d, brivaracetam 300 mg/d, valproate 1,600 mg/d, and various benzodiazepines did not resolve the SE. Due to ongoing refractory SE and following an unremarkable echocardiography, treatment was initiated with FFA, with an initial dose of 10 mg/d (0.22 mg/kg body weight [bw]) and fast up-titration to 26 mg/d (0.58 mg/kg bw) within 10 days. Subsequently, the patient experienced a resolution of SE within 4 days, accompanied by a notable improvement in clinical presentation and regaining her mobility, walking with the assistance of physiotherapists. In the three cases reported in the literature, DS patients with SE were treated with FFA, and a cessation of SE was observed within a few days. No treatment-emergent adverse events were observed during FFA treatment in any of the four cases.
Conclusions: Based on the reported cases, FFA might be a promising option for the acute treatment of SE in patients with DS and LGS. Observational data show a decreased SE frequency while on FFA, suggesting a potentially preventive role of FFA in these populations.
Key points
* We summarize four cases of refractory status epilepticus (SE) successfully treated with fenfluramine.
* Refractory SE resolved after 4–7 days on fenfluramine.
* Swift fenfluramine up-titration was well-tolerated during SE treatment.
* Treatment-emergent adverse events on fenfluramine were not observed.
* Fenfluramine might be a valuable acute treatment option for SE in Dravet and Lennox–Gastaut syndromes.
Purpose: Seizures pose a significant burden in patients with primary and secondary brain tumors during the end-of-life period. A wide range of 6 to 56% of clinically observed epileptic seizures at the end of life has been reported. We aimed to analyse the incidence of epileptic seizures at the end of life in brain tumor patients more accurately using not only clinical but also electrophysiological findings.
Methods: This retrospective, single center study included brain tumor patients who died during the stay on the ward or within 7 days after discharge between 01/2015 and 08/2020. Clinical observation of seizures derived from the original medical records and EEG findings (within 45 days prior to death) were analyzed to determine the incidence of seizures in that period.
Results: Of the 68 eligible patients, 50 patients (73.5%) suffered from seizures within 45 days prior to death, of which n = 24 had a status epilepticus. The diagnosis of seizures/ status epilepticus was determined either by the presentation of clinical signs in 45 patients and if not, by the detection of a (possible) non-convulsive status epilepticus in the EEG of five patients.
Conclusion: In the presence of neurologically trained staff and with the frequent use of routine EEG, we were able to identify seizures and to distinguish status epilepticus from encephalopathy/ hypoactive delirium. We detected a higher incidence of seizures and status epilepticus at the end of life in neurooncological patients than previously reported.
The article investigates the results obtained from numerical simulations and experimental tests concerning the propagation of guided waves in corroded steel plates. Developing innovative methodologies for assessing corrosion-induced degradation is crucial for accurately diagnosing offshore and ship structures exposed to harsh environmental conditions. The main aim of the research is to analyze how surface irregularities affect wave propagation characteristics. An investigation was conducted for antisymmetric fundamental mode A0. Specifically, the study examines the asymmetrical wavefronts generated by nonuniform thickness in damaged specimens. Initially, numerical analysis explores the impact of thickness variation on wave field symmetry. Corroded plates with varying levels of degradation are modeled using the random fields approach, with degradation levels ranging from 0 % to 60 %. Subsequently, the research investigates how the standard deviation of thickness distribution (from 5 % to 20 % of the initial thickness) and excitation frequency (from 50 to 150 kHz) influence recorded signals and the shape of reconstructed wavefronts. Each scenario compares wavefront symmetry levels estimated using rotational and bilateral symmetry degrees as indicative parameters. The numerical simulations are complemented by experimental tests conducted on plates with three different degradation levels. The results demonstrate the efficacy of the proposed wave field analysis approach for assessing structural integrity, as evidenced by the agreement between numerical predictions and experimental observations.
Oncogenic transformation of lung epithelial cells is a multistep process, frequently starting with the inactivation of tumour suppressors and subsequent development of activating mutations in proto-oncogenes, such as members of the PI3K or MAPK families. Cells undergoing transformation have to adjust to changes, including altered metabolic requirements. This is achieved, in part, by modulating the protein abundance of transcription factors. Here, we report that the ubiquitin carboxyl-terminal hydrolase 28 (USP28) enables oncogenic reprogramming by regulating the protein abundance of proto-oncogenes such as c-JUN, c-MYC, NOTCH and ∆NP63 at early stages of malignant transformation. USP28 levels are increased in cancer compared with in normal cells due to a feed-forward loop, driven by increased amounts of oncogenic transcription factors such as c-MYC and c-JUN. Irrespective of oncogenic driver, interference with USP28 abundance or activity suppresses growth and survival of transformed lung cells. Furthermore, inhibition of USP28 via a small-molecule inhibitor resets the proteome of transformed cells towards a ‘premalignant’ state, and its inhibition synergizes with clinically established compounds used to target EGFRL858R-, BRAFV600E- or PI3KH1047R-driven tumour cells. Targeting USP28 protein abundance at an early stage via inhibition of its activity is therefore a feasible strategy for the treatment of early-stage lung tumours, and the observed synergism with current standard-of-care inhibitors holds the potential for improved targeting of established tumours.
Background and objectives: Our study aimed at examining the long-time inflammatory effects of rheumatoid arthritis (RA) as chronic immune-mediated disease on pain sensation and neuropathy development compared to healthy subjects (HS).
Methods: We used the quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain and Electroencephalography (EEG)–based contact heat evoked potentials (CHEPs) before and after topical capsaicin application. We recruited 16 RA patients in remission or low disease activity state (mean age: 59.38 years [± 10.18]) and 16 healthy subjects (mean age: 56.69 years [± 8.92]).
Results: The application of capsaicin cream on the thigh provoked a stronger effect in HS for both mechanical and heat pain thresholds (MPT and HPT, resp.), according to the area under the receiver operation characteristic (AUROC) (HS: HPT: 0.8965, MPT: 0.7402; RA: HPT: 0.7012, MPT: 0.6113). We observed contrary effects regarding changes in CHEPs (HS: g*max = − 0.65; RA patients: g*max = 0.72).
Conclusion: As the overall effect of topical capsaicin application was higher in HS for QST, we suggest the existence of a sensitization of TRPV1 channels in RA patients caused by long-time chronical inflammation, despite a lack of clinical signs of inflammation due to adequate treatment. The effect in CHEPs probably uncovers neuropathic symptoms. The effect of topical capsaicin on HPTs and CHEPs can act as a marker for the extent of sensitization and the development of neuropathic symptoms. Further studies are needed to prove if our proposed method can act as a marker for the success of anti-inflammatory treatment.
The ligand-sensing transcription factor Nurr1 emerges as a promising therapeutic target for neurodegenerative pathologies but Nurr1 ligands for functional studies and therapeutic validation are lacking. Here pronounced Nurr1 modulation by statins for which clinically relevant neuroprotective effects are demonstrated, is reported. Several statins directly affect Nurr1 activity in cellular and cell-free settings with low micromolar to sub-micromolar potencies. Simvastatin as example exhibits anti-inflammatory effects in astrocytes, which are abrogated by Nurr1 knockdown. Differential gene expression analysis in native and Nurr1-silenced cells reveals strong proinflammatory effects of Nurr1 knockdown while simvastatin treatment induces several neuroprotective mechanisms via Nurr1 involving changes in inflammatory, metabolic and cell cycle gene expression. Further in vitro evaluation confirms reduced inflammatory response, improved glucose metabolism, and cell cycle inhibition of simvastatin-treated neuronal cells. These findings suggest Nurr1 involvement in the well-documented but mechanistically elusive neuroprotection by statins.
Human feline leukaemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and FLVCR2) are members of the major facilitator superfamily1. Their dysfunction is linked to several clinical disorders, including PCARP, HSAN and Fowler syndrome2,3,4,5,6,7. Earlier studies concluded that FLVCR1 may function as a haem exporter8,9,10,11,12, whereas FLVCR2 was suggested to act as a haem importer13, yet conclusive biochemical and detailed molecular evidence remained elusive for the function of both transporters14,15,16. Here, we show that FLVCR1 and FLVCR2 facilitate the transport of choline and ethanolamine across the plasma membrane, using a concentration-driven substrate translocation process. Through structural and computational analyses, we have identified distinct conformational states of FLVCRs and unravelled the coordination chemistry underlying their substrate interactions. Fully conserved tryptophan and tyrosine residues form the binding pocket of both transporters and confer selectivity for choline and ethanolamine through cation–π interactions. Our findings clarify the mechanisms of choline and ethanolamine transport by FLVCR1 and FLVCR2, enhance our comprehension of disease-associated mutations that interfere with these vital processes and shed light on the conformational dynamics of these major facilitator superfamily proteins during the transport cycle.
Die Epoche des Vormärz ist von einer Intensivierung staatlicher Geheimdiensttätigkeit sowie einer Professionalisierung und Institutionalisierung der staatlichen Überwachungs- und Zensurbehörden gekennzeichnet. Die in dieser Zeit sich herausbildenden Kontrolltechniken und -strukturen bildeten die Grundlage für spätere Überwachungsregime. Es war eine Zäsur für die deutsche Geschichte generell und für die Geschichte der deutschen Inlandsspionage im Besonderen. Von 1833 bis 1842 wurden die Ermittlungen des Deutschen Bundes gegen politisch Andersdenkende durch die Bundeszentralbehörde in Frankfurt am Main und das Mainzer Informationsbüro durchgeführt; in Preußen wurde 1833 die zweite Ministerialkommission ins Leben gerufen, die bereits 1819 bis 1828 aktiv gewesen war und sämtliche "politischen Umtriebe" in Preußen überwachte. [...] Die staatlichen Überwachungsapparate funktionierten nur mit Hilfe von zahlreichen beteiligten Menschen: von hohen Ministerialbeamten über Polizeibeamte bis zu informellen Zuträgern, die unter vielen Namen bekannt sind - Konfidenten, Informanten, Agenten, V-Leute, Spitzel. Über die Biographien und die konkreten Tätigkeiten dieser untergeordneten Akteure liegen bislang nur verstreute Forschungen vor. Der vorliegende Aufsatz stellt einen von ihnen vor - den Literaten und geheimen Informanten Joel Jacoby. Joel Jacoby (1811-1863) war eine der berüchtigtsten Figuren des Vormärz. Um sein Leben und Wirken als preußischer Spitzel rankten sich schon zu Lebzeiten zahlreiche Legenden. Doch bislang gab es nur wenig gesichertes Faktenwissen darüber, worin sein geheimdienstliches Wirken eigentlich genau bestand. Neu aufgefundene Geheimberichte, die Jacoby an die preußischen Überwachungsbehörden sandte, erlauben nun erstmals Einblicke in seine Tätigkeit. Jacobys Berichte stellen einen Schatz sowohl für die Erforschung seiner Biographie als auch des Geheimdienstwesens im Vormärz dar. Ich gebe im Folgenden einen ersten Überblick über die Berichte aus der Frühzeit von Jacobys Spitzeltätigkeit. Sie führen vor Augen, wie umfangreich, akribisch, aber auch widersprüchlich die Arbeit eines Agenten sein konnte, der die Rollen eines Verfolgers und Verfolgten, eines Spitzels und Schriftstellers in seiner Person vereinte. Es wird sich zeigen, welch großen Stellenwert Literatur und Presse für die Agententätigkeit hatte und wie sehr die Berichte an dem jeweiligen Empfänger ausgerichtet waren.
Charles Cros, Erfinder technischer Reproduzierbarkeit von Wahrnehmung in Nachmärz und Moderne
(2023)
Charles Cros (1842-1888) verkörpert den Weg der französischen Lyrik von der Spätromantik über Parnass und Symbolismus zur Moderne in überraschender Dichte, anders, aber nicht weniger typisch als Verlaine, Rimbaud und Mallarmé. [...] Die naturwissenschaftlichen Erfindungen von Charles Cros sind durchweg kommunikativer Natur und zielen auf die Reproduzierbarkeit von Sinneseindrücken wie seine Poesie auf die "Wiederholbarkeit von Träumen". Der Zusammenhang von technischer Reproduzierbarkeit - hier durchaus im Sinne von Walter Benjamins einschlägigem Essay verstanden - und der lyrischen 'Chansons perpétuelles' von Cros ist indessen noch niemals untersucht worden.
Der eurozentrische Blick des 18. und 19. Jahrhunderts, den es hier zu untersuchen gilt, definiert und interpretiert das Wahrgenommene über vergleichende Studien. Stets steht eine Differenz in der Subjekt-Objekt Beziehung zwischen Beobachtendem und Wahrgenommenem. Dies gelingt am ehesten, wenn das Objekt der Betrachtung abstrahiert und verallgemeinert und zugleich aus einer sicher wirkenden Distanz beschrieben wird. Beschreibungen von Menschen verschiedener Herkunft basieren auf Vergleichen, deren Kriterien die Untersuchungsergebnisse von vornherein festlegen. Sie fokussieren sich auf Körpermerkmale und deren unterstellte Einflüsse auf intellektuelle und kulturelle Entwicklungsmöglichkeiten. Sie betrachten gesellschaftliche Strukturen und ziehen daraus ihre verallgemeinernden Schlüsse. Solche Untersuchungen entstehen auf unterschiedlichen Ebenen: Im bildungsbürgerlichen Haushalt finden sich populärwissenschaftliche Publikationen wie Lexika für Erwachsene und Kinder. Die sich etablierende Anthropologie bedient sich ebenfalls der Vergleichsmodelle in der Beschreibung des Andersseins. Versuche, die Perspektive zu ändern und einen kulturellen Transfer überhaupt erst zu denken, lenken den Blick auf ein weiteres wichtiges Phänomen der Wahrnehmung in Selbsterkenntnis. Als Quellentexte und Anschauungsmaterialien sind solche Publikationen zusammengestellt, in welchen die Differenz zwischen Europäer:innen und Afrikaner:innen herausgearbeitet wird. Der afrikanische Kontinent gewinnt im 19. Jahrhundert zunehmend an Bedeutung. Das Innere des Kontinents lockt Forschungsreisende, Missionare und später Kolonialmächte an. Aus den Begegnungen und Beschreibungen leiten sich nicht nur Bilder, sondern zugleich Argumentationslinien für europäische Handlungsstrategien ab, die bis heute nachwirken.
Was in diesem Aufsatz unternommen werden soll, lässt sich als eine Phänomenologie der pathischen Wahrnehmung charakterisieren: Es geht um die Wahrnehmung, insofern sie als ein leibliches Widerfahrnis erlebt wird. Genauer gesagt: In der Wahrnehmung geschieht eine Einwirkung des Wahrgenommenen auf den Wahrnehmenden, also eine angenehme oder unangenehme Einwirkung des Wahrnehmungsobjekts auf das Wahrnehmungssubjekt, die sich als phänomenaler Bestand erfassen lässt. Das Widerfahrnis gehört daher selbst zum Wahrnehmungsgehalt des wahrnehmenden Subjekts, und nur insoweit ist es das Thema einer Phänomenologie der pathischen Wahrnehmung. [...] Das Ziel dieser Untersuchung besteht darin, die Aufmerksamkeit auf bestimmte Qualitäten der Wahrnehmungsobjekte zu richten, welche in einer jeden Wahrnehmungsphilosophie unter den Tisch fallen, welche sich üblicherweise an epistemischen Fragestellungen orientiert und die Wahrnehmung deshalb primär als sinnliche Erkenntnis befragt. [...] Eine entscheidende Hürde, die einer Phänomenologie der pathischen Wahrnehmung im Wege steht, ist nun jene bereits erwähnte und in Philosophie und Wissenschaft weit verbreitete Auffassung, Wahrnehmung sei sinnliche Erkenntnis und sonst gar nichts - zumindest nichts, was einer philosophischen Untersuchung wert sei. Es bietet sich an, diese Hürde als Primat der Erkenntnis zu charakterisieren. Allerdings ist dies nicht die einzige Hürde, die es zu überwinden gilt, um die Philosophie weiter ins Dickicht der Wahrnehmung hinein zu führen. Es lassen sich immerhin noch zwei weitere unterscheiden, die als Primat der Praxis und Primat des Leibes bezeichnen werden können. Von einem Primat der Praxis lässt sich dort sprechen, wo eine pragmatische Verkürzung in dem Sinne vorliegt, dass Widerfahrnisse nur als Widerstände gegen unser Handeln berücksichtigt werden und das Unangenehme sich damit auf das Hinderliche reduziert. Demgegenüber soll von einem Primat des Leibes, bei dem die häufige Leibvergessenheit der Wahrnehmungsphilosophie geradezu durch eine Leibversessenheit überkompensiert wird, dann die Rede sein, wenn zwar pathische Qualitäten im Mittelpunkt stehen, diese jedoch lediglich als eigenleibliche Zustände verstanden und damit von jeglicher Wahrnehmung weltlicher Objekte abgetrennt werden. In den nun anschließenden Überlegungen sollen zunächst durch eine kritische Abgrenzung gegenüber den genannten drei Hürden die Konturen eines alternativen wahrnehmungsphilosophischen Ansatzes tentativ sichtbar werden. Nach dieser kritischen Auseinandersetzung folgt dann der positive Gegenentwurf, in dem anhand von konkreten Beispielen der Versuch einer Phänomenologie der pathischen Wahrnehmung unternommen wird.
Der Mediziner und Psychiater Erwin Straus (1891-1975) hat für die Welt der Wahrnehmung eine eigene Ästhesiologie, in der er Wahrnehmung selbst als ein leibliches Empfinden differenziert, entwickelt und gewinnt über seine Kritik der Trennung von Wahrnehmung und Wirklichkeit ein eigenes Konzept der kommunikativen Struktur von Wahrnehmung und Welt jenseits der polaren Struktur von Subjekt und Objekt. [...] Im Folgenden werde ich Straus' Ästhesiologie in drei Schritten vorstellen: Beginnen werde ich mit den leiblichen wie welthaften Grundlagen der Wahrnehmung im Empfinden, dem inkarnierten Subjekt in pathischer und gnostischer Kommunikation mit der Welt, wie Straus dies differenziert. Zweitens bauen sich aus der raum-zeitlichen Struktur dieser Kommunikation Erfahrungen in einem historischen - einem Lebenskontext - auf; hier rekurriert Straus dann auch auf das spezifisch menschliche Wahrnehmen. Abschließend werde ich Straus' Entwicklung einer aus der Situation des Wahrnehmenden gewonnenen Theorie der Norm vorstellen, mit der er nicht nur auf dem Feld der Psychiatrie psychopathologisch wie auch ärztlich argumentiert, sondern auch generell für die Grundlage sinnhafter Erfahrungen unserer Wirklichkeit als sinnliche Subjekte in einer Welt für Selbst- und Fremdwahrnehmung, um gegen Reduktionismen mancher empirischen Forschungen wieder den Reichtum einer gemeinsam erlebten Welt wiederzugewinnen: Als Reichtum der phänomenalen Vielfalt, der unreduzierbaren Eigen- und Andersheit, nicht als Regel, sondern als Sinn der Sinne. Eben jenes, worum Büchner und die Personen seiner Vormärz-Dramen ringen.
Der Gestank der Armen : philosophische Notizen zur Topografie eines moralisch anästhesierten Sinnes
(2023)
In seiner reich instrumentierten Kulturgeschichte des Geruchs beschreibt der französische Historiker Alain Corbin die Großstädte des 18. Jahrhunderts als Orte olfaktorischer Zumutungen. Als der junge Rousseau 1731 nach Paris kam, fand er ein "Amphitheater von Latrinen" vor. Selbst in den Tuilerien und in den Gärten des Palais Royal konnte man den übelerregenden Dunstschwaden, die von den Ufern der Seine herüberwehten, nicht entgehen. Paris stank buchstäblich zum Himmel. [...] Noch taten sich Standesunterschiede nicht in der Abwesenheit von schlechten Gerüchen kund. Die Ordnung von Macht und Stand fand ihren Ausdruck in einer Steigerung "sozialer Sichtbarkeit", um die sich Angehörige höherer Stände ohnehin nicht besorgen mussten, weil sie ihnen qua Geburt schon immer gegeben war. Man musste sich nicht waschen, um das gemeine Volk in seine Schranken zu weisen. Selbst der Souverän stank. [...] Alain Corbin beschreibt die Phase von der zweiten Hälfte des 18. bis zum Ende des 19. Jahrhunderts als eine Epoche der Desodorierung, die mit einem grundlegenden Wandel in der Wahrnehmung, Bewertung und Interpretation von Gerüchen einhergeht. Der Fokus verschiebt sich "vom Lebenden zum Sozialen", wie Corbin betont. Die Geruchstoleranz gegenüber der sozialen Mitwelt sinkt. Hygiene und Sauberkeit markieren zunehmend "soziale Positionen, soziale Unterschiede und soziale Pflichten". Insbesondere der öffentliche Raum wird zum Schauplatz hygienischer Disziplinierung. [...] Wenngleich sich Corbins Analysen nur zeitverschoben auf das vormärzliche Deutschland übertragen lassen, wächst auch hier mit den demografischen und industriellen Umwälzungen das Interesse an 'sozialen' Gerüchen. Gerüche werden zu affektiven Operatoren "sozialer Fremd-eigen Differenzen".
Die folgenden Überlegungen zielen darauf ab, den Übergangscharakter der Erkenntnislehre Feuerbachs auszuweisen, die einerseits an die objektivistische Linie der empiristisch-sensualistischen Philosophie unter den französischen Materialisten anschließt und andererseits auf die ökologische Fundierung des menschlichen Bewusstseins und seiner Leistungen vorausweist, die seit dem letzten Drittel des neunzehnten Jahrhunderts in Philosophie und Wissenschaften Verbreitung gefunden und der aktuellen, in Philosophie und Neurowissenschaften vertretenen Embodiment-Forschung den Weg bereitet hat. So stehen Feuerbachs 'reformatorische' Bemühungen um eine Erneuerung der deutschsprachigen Philosophie nach dem Idealismus in einer bislang noch unbeachtet gebliebenen Fernbeziehung mit den Bemühungen der Gegenwart um eine Revision des klassischen Leib-Seele-Dualismus. Zur Veranschaulichung des Kerngehalts von Feuerbachs französischen Vorläufern greife ich zunächst auf die Radikalisierung des Empirismus einerseits durch den erkenntnistheoretischen Sensualismus und andererseits durch den physiologischen Materialismus zurück, indem ich exemplarisch Etienne Bonnot de Condillacs "Traité des sensations" und Julien Offray de La Mettrie's "L'Homme Machine" als realtypische Ausdrucksgestalten dieser französischen Entwicklungslinie darstelle (1). In einem zweiten Schritt zeige ich Gemeinsamkeiten und Differenzen Ludwig Feuerbachs im Verhältnis zu dieser sensualistischmaterialistischen Traditionslinie des empiristischen Philosophierens auf (2) und schließe damit, wie Feuerbachs Umformung dieser Tradition zugleich auf die Ökologisierung der Erkenntnistheorie um 1900 und vermittelt darüber auch auf die gegenwärtige Forschung zur Philosophie der Verkörperung vorausweist (3).
So unterschiedlich auch immer J. G. Fichtes und Hegels Auffassung des Ich sind, unterscheidet sich I. H. Fichte - der posthume Herausgeber der Werke seines Vaters - in der "Erste[n] Abtheilung: Das Erkennen als Selbsterkennen" seiner Grundzüge zum Systeme der Philosophie 1833 in mehreren Hinsichten, die für den Vormärz charakteristisch sind, noch stärker von ihnen als die beiden voneinander: 1. Am Anfang dessen Entwicklung steht das Ich weder Sachen gegenüber noch setzt es ein Objekt sich gegenüber, sondern das Ich wird von einer Mannigfaltigkeit der Empfindung geradezu besetzt. 2. Die Entwicklung des Ich beginnt nicht mit einer völligen Aktivität, sondern mit einer völligen Passivität, aus der allmählich (keine unbegrenzte) Aktivität entsteht. 3. Das Ich ist am Anfang dessen Entwicklung Mannigfaltigkeit; es konstituiert sich als Ich erst allmählich. 4. Das Ich ist am Anfang weder ein rein universelles Subjekt, in dem Sinne, in dem jedes Ich jedem Ich gleich ist, sondern das Ich ist individuell. Auch im Laufe dessen Entwicklung entsteht kein reines, universelles Ich, sondern es bleibt immer individuell. 5. Anders als das reine Ich bei J. G. Fichte und Hegel steht I. H. Fichtes Ich am "Anfang" seines "System der Philosophie". Die Wahrnehmung steht als "Erste Epoche" am Anfang der Entwicklung des Ich. Die erste Epoche enthält wiederum drei "Stufen" der Wahrnehmung.
Das Wachsein ist kein Privileg, sondern ein besonderes Ergebnis förderlicher Umstände. Wir können die Figurationen solcher Privilegien, d. h. auch die Umstände, auf denen sie beruhen, nicht verlassen, ohne dass Elemente starker Dysfunktion den Frieden dieser Anordnung einmal gestört hätten. Im 19. Jahrhundert sind die Sinne nicht nur bezogen auf das, was sie wahrnehmen, sondern tangieren jenseits der Inhaltsschübe die Strukturen und Selbstverhältnisse derjenigen, die zu diesem Zeitpunkt das symbolische Medium der Sprache verwenden. Im Vormärz störte eine Krise des Autoritarismus die unbefangene Herrschaft; Metternich et al. wurden zu Chiffren dessen, was eine staatliche Ordnung nicht mehr reibungslos beförderte, sondern im Zuge revolutionierender Prozesse Fragen aufwarf: Nach Geltung, der Verlässlichkeit der eigenen Wahrnehmung, die bislang meist von autoritären Strukturen geleitet worden war, nach möglichen Eigenanteilen an dem, was die politische Struktur bisher hergegeben hatte. Strukturwandel trat als Wahrnehmungswandel in die Geschichte ein. Die Sinne und allgemein die Wahrnehmungsfähigkeit werden im Vormärz im Gesehenen herausgefordert. Wahrnehmung ist eine 'contested area', ein umkämpftes Gebiet, in dem sich alte und neue Wahrnehmungsformen überlagern und kreuzen. Gezeigt werden soll, dass Wahrnehmung, mit Erwin Straus, ästhesiologisch aufzufassen ist, d. h. dass im alltäglichen Vollzug des sinnlichen Erlebens unser Interesse beim Gegenstand, der Welt, dem Anderen ist, nicht nur beim bestätigenden Sehen des Gesehenen, sondern dem Gesehenen als Quelle möglicher Änderung. Es gibt immer die Möglichkeit der Bewegung, die Möglichkeit, sich zum Wahrgenommenen zu verhalten. In diesem Sinne sind die Bewegung und Bewegtheit des Vormärz ein politisches Phänomen: aus den sensuellen Erfahrungen folgt etwas. Die bewegte und bewegende Beziehung zum Wahrgenommenen begründet im Vormärz einen Anspruch auf Partizipation, der einem Wachwerden der Sinne gleichkommt.
Die Vormärzforschung befasste sich in der Vergangenheit vor allem mit Themen des Liberalismus, insbesondere mit juristischen Fragen und der Gründung einer verfassungsgebenden Versammlung. Dabei wurde die Kluft zwischen einem - oft akademisch geschulten - 'gehobenen Bürgertum' und der großen Mehrzahl der Menschen in Dörfern, Kleinstädten und einer sich noch vielfach als Heimarbeit etablierenden Industrie oft übersehen. Diese Arbeit wird sich auf die allmählich einsetzende Wahrnehmung dieser Mehrzahl konzentrieren, mit dem Ziel, ihr politisches Verständnis und ihren Willen zur demokratischen Partizipation zu analysieren. Hierbei geht es vornehmlich um ein "Gewahrwerden sinnlich vermittelter Gegebenheiten" und ihrer geistigen Verarbeitung. Bei diesem Prozess wird das geistig rationale 'Verständnis' der Gegebenheiten erweckt und zu einer empirisch vermittelten 'Sicht' der Dinge hingeführt. Bei solchen Sinneswahrnehmungen geht es in erster Linie um das Sehvermögen; das von den Augen Gesehene wird über Nerven an das Gehirn transportiert, wir machen uns ein 'Bild' davon, das im weiteren Verlauf zu einer 'Ansicht' oder 'Anschauung' werden kann. Ähnliches gilt für andere Sinneseinwirkungen: Das 'Gefühlte' komprimiert sich zu einem 'Gefühl', wobei neben anderen Sinneswahrnehmungen auch ein mentaler Prozess mit im Spiel ist. Von der Forschung wenig beachtet ist eine Umkehrung dieses Vorgangs: Mental Wahrgenommenes kann über die Imagination auch sinnlich anschaulich werden, ein Prozess, der vor allem in der Romantik häufig stattfand. Eine genauere Erörterung der Begriffe 'Wahrnehmung' oder 'Perzeption' ist hier nicht vorgesehen, doch wird im Kontext der dargestellten Beispiele auf weitere, vor allem literarische und philosophische Diskussionen dieser Begriffe eingegangen.
Wahrnehmung wurde zu Beginn des 20. Jahrhunderts bestimmt als "Organ unseres ursprünglichen Welt-Erlebens." Das ursprüngliche Welterleben war das des Flaneurs, der mit allen Sinnen Umwelt wahrnimmt, um sich zu situieren und aus dieser Verortung Sicherheit und Anderssein zu gewinnen; die Verortung war aber auch über die Individualebene hinaus von politischer, sozialer, ökonomischer und kultureller Bedeutung. Man greift nicht zu hoch, wenn der Vormärz als Zeitspanne betrachtet wird, in der eine vollere Realität in sehr spezifischer Weise greifbar wurde. Die Vielschichtigkeit der Vormärz-Welt war dabei eine konstanter Innovation, die eine Initiierung jener Selbstbilder bedeutete, die über das Wahrnehmen bestätigt wurden, das selbst ein anderes geworden war. Nicht mehr informierte Wahrnehmung über die tautologisch so genannten sozialen Tatsachen; sie schuf diese vielmehr um und damit neu - das Organ des Welterlebens wirkte hier auf die Welt ein und musste Erlebnisse nicht mehr erleiden. Die Erfahrung der Welt-Erlebnisse bestand auch darin, die Sinne als sinnenöffnend zu sehen, indem die theoretische Vorrangstellung des Informationsaspekts der Wahrnehmung zurücktrat und Indices von Engagement, Eingreifen und Emanzipation deutlich werden konnten. Dies bedeutete, eine Form des "Wirklichkeitskontakts" zu suchen, die bisher nicht bestanden hatte. War der Kontakt vorher so geschehen, dass die Sinne eine bestätigende Funktion den sozialen und politischen Valeurs gegenüber einnahmen, die bezogen auf Emanzipationsprozesse und deren Möglichkeit einer Schließung gleichkam, öffnete nun die Veränderung der Wahrnehmung neue Formen des Wirklichkeitskontakts. In diesem Kontakt war vor allem entscheidend, dass nun die Bedingungen der Wahrnehmung ersichtlich wurden, sich als veränderbar auswiesen und nicht mehr im umfassenden Konstrukt "Wahrnehmung" aufgingen.
In natural environments, background noise can degrade the integrity of acoustic signals, posing a problem for animals that rely on their vocalizations for communication and navigation. A simple behavioral strategy to combat acoustic interference would be to restrict call emissions to periods of low-amplitude or no noise. Using audio playback and computational tools for the automated detection of over 2.5 million vocalizations from groups of freely vocalizing bats, we show that bats (Carollia perspicillata) can dynamically adapt the timing of their calls to avoid acoustic jamming in both predictably and unpredictably patterned noise. This study demonstrates that bats spontaneously seek out temporal windows of opportunity for vocalizing in acoustically crowded environments, providing a mechanism for efficient echolocation and communication in cluttered acoustic landscapes.
Forest wildflowers bloom earlier as Europe warms: lessons from herbaria and spatial modelling
(2022)
Today plants often flower earlier due to climate warming. Herbarium specimens are excellent witnesses of such long-term changes. However, the magnitude of phenological shifts may vary geographically, and the data are often clustered. Therefore, large-scale analyses of herbarium data are prone to pseudoreplication and geographical biases.
We studied over 6000 herbarium specimens of 20 spring-flowering forest understory herbs from Europe to understand how their phenology had changed during the last century. We estimated phenology trends with or without taking spatial autocorrelation into account.
On average plants now flowered over 6 d earlier than at the beginning of the last century. These changes were strongly associated with warmer spring temperatures. Flowering time advanced 3.6 d per 1°C warming. Spatial modelling showed that, in some parts of Europe, plants flowered earlier or later than expected. Without accounting for this, the estimates of phenological shifts were biased and model fits were poor.
Our study indicates that forest wildflowers in Europe strongly advanced their phenology in response to climate change. However, these phenological shifts differ geographically. This shows that it is crucial to combine the analysis of herbarium data with spatial modelling when testing for long-term phenology trends across large spatial scales.
Background: Despite advances in treatment of patients with non-small cell lung cancer, carriers of certain genetic alterations are prone to failure. One such factor frequently mutated, is the tumor suppressor PTEN. These tumors are supposed to be more resistant to radiation, chemo- and immunotherapy.
Results: We demonstrate that loss of PTEN led to altered expression of transcriptional programs which directly regulate therapy resistance, resulting in establishment of radiation resistance. While PTEN-deficient tumor cells were not dependent on DNA-PK for IR resistance nor activated ATR during IR, they showed a significant dependence for the DNA damage kinase ATM. Pharmacologic inhibition of ATM, via KU-60019 and AZD1390 at non-toxic doses, restored and even synergized with IR in PTEN-deficient human and murine NSCLC cells as well in a multicellular organotypic ex vivo tumor model.
Conclusion: PTEN tumors are addicted to ATM to detect and repair radiation induced DNA damage. This creates an exploitable bottleneck. At least in cellulo and ex vivo we show that low concentration of ATM inhibitor is able to synergise with IR to treat PTEN-deficient tumors in genetically well-defined IR resistant lung cancer models.
We conducted a systematic review investigating the efficacy and tolerability of adrenocorticotropic hormone (ACTH) and corticosteroids in children with epilepsies other than infantile epileptic spasm syndrome (IESS) that are resistant to anti-seizure medication (ASM). We included retrospective and prospective studies reporting on more than five patients and with clear case definitions and descriptions of treatment and outcome measures. We searched multiple databases and registries, and we assessed the risk of bias in the selected studies using a questionnaire based on published templates. Results were summarized with meta-analyses that pooled logit-transformed proportions or rates. Subgroup analyses and univariable and multivariable meta-regressions were performed to examine the influence of covariates. We included 38 studies (2 controlled and 5 uncontrolled prospective; 31 retrospective) involving 1152 patients. Meta-analysis of aggregate data for the primary outcomes of seizure response and reduction of electroencephalography (EEG) spikes at the end of treatment yielded pooled proportions (PPs) of 0.60 (95% confidence interval [CI] 0.52–0.67) and 0.56 (95% CI 0.43–0.68). The relapse rate was high (PP 0.33, 95% CI 0.27–0.40). Group analyses and meta-regression showed a small benefit of ACTH and no difference between all other corticosteroids, a slightly better effect in electric status epilepticus in slow sleep (ESES) and a weaker effect in patients with cognitive impairment and “symptomatic” etiology. Obesity and Cushing's syndrome were the most common adverse effects, occurring more frequently in trials addressing continuous ACTH (PP 0.73, 95% CI 0.48–0.89) or corticosteroids (PP 0.72, 95% CI 0.54–0.85) than intermittent intravenous or oral corticosteroid administration (PP 0.05, 95% CI 0.02–0.10). The validity of these results is limited by the high risk of bias in most included studies and large heterogeneity among study results. This report was registered under International Prospective Register of Systematic Reviews (PROSPERO) number CRD42022313846. We received no financial support.
Key points
* Systematic review resulting in low to moderately solid evidence on the efficacy and tolerability of adrenocorticotropic hormone (ACTH) and corticosteroid treatment in children with epilepsy other than infantile spasms.
* Meta-analysis based on aggregate data from 2 controlled prospective, 5 uncontrolled prospective, and 31 retrospective studies.
* Pooled data showing a seizure response in 60% and electroencephalography (EEG) response in 56% of patients, with no major differences between drugs. However, 30%–40% of patients relapse after the cessation of treatment.
* The most frequent adverse effects are obesity and Cushing's syndrome, occurring in 70% of patients under continuous treatment for some weeks, but in less than 10% undergoing pulsed, intermittent regimens.
* More prospective, randomized-controlled studies are needed to improve the level of evidence and define the optimal doses and treatment duration.
Background: Epilepsy surgery is an established treatment for drug-resistant focal epilepsy (DRFE) that results in seizure freedom in about 60% of patients. Correctly identifying an epileptogenic lesion in magnetic resonance imaging (MRI) is challenging but highly relevant since it improves the likelihood of being referred for presurgical diagnosis. The epileptogenic lesion’s etiology directly relates to the surgical intervention’s indication and outcome. Therefore, it is vital to correctly identify epileptogenic lesions and their etiology presurgically.
Methods: We compared the final histopathological diagnoses of all patients with DRFE undergoing epilepsy surgery at our center between 2015 and 2021 with their MRI diagnoses before and after presurgical diagnosis at our epilepsy center, including MRI evaluations by expert epilepsy neuroradiologists. Additionally, we analyzed the outcome of different subgroups.
Results: This study included 132 patients. The discordance between histopathology and MRI diagnoses significantly decreased from 61.3% for non-expert MRI evaluations (NEMRIs) to 22.1% for epilepsy center MRI evaluations (ECMRIs; p < 0.0001). The MRI-sensitivity improved significantly from 68.6% for NEMRIs to 97.7% for ECMRIs (p < 0.0001). Identifying focal cortical dysplasia (FCD) and amygdala dysplasia was the most challenging for both subgroups. 65.5% of patients with negative NEMRI were seizure-free 12 months postoperatively, no patient with negative ECMRI achieved seizure-freedom. The mean duration of epilepsy until surgical intervention was 13.6 years in patients with an initial negative NEMRI and 9.5 years in patients with a recognized lesion in NEMRI.
Conclusions: This study provides evidence that for patients with DRFE—especially those with initial negative findings in a non-expert MRI—an early consultation at an epilepsy center, including an ECMRI, is important for identifying candidates for epilepsy surgery. NEMRI-negative findings preoperatively do not preclude seizure freedom postoperatively. Therefore, patients with DRFE that remain MRI-negative after initial NEMRI should be referred to an epilepsy center for presurgical evaluation. Nonreferral based on NEMRI negativity may harm such patients and delay surgical intervention. However, ECMRI-negative patients have a reduced chance of becoming seizure-free after epilepsy surgery. Further improvements in MRI technique and evaluation are needed and should be directed towards improving sensitivity for FCDs and amygdala dysplasias.
Background: Patients with epilepsy often require a specialized treatment, which may differ because of the responsibility of the federal states for healthcare policy in Germany.
Objective: State-specific differences in healthcare structures based on inpatient hospital cases of epilepsy patients between 2000 and 2020 in relation to specialized treatment offers.
Material and methods: The inpatient hospital cases of the German federal states were evaluated using the Friedman test and time series trend analysis. A state-specific inpatient undertreatment or overtreatment of inpatient hospital cases outside the registered state was analyzed by comparing residence-related and treatment site-related case numbers with a threshold of ±5%.
Results: After age adjustment, significantly more inpatient cases were found in the “new states” compared to the “old states” (p < 0.001); the highest number of cases nationwide was found in Saarland with 224.8 ± 11.5 cases per 100,000 inhabitants. The trend analysis showed an increase in cases until the end of 2016 with a trend reversal from 2017 and a further significant decrease in hospital cases in the COVID year 2020. A relative inpatient undertreatment was shown for Brandenburg, Lower Saxony, Rhineland-Palatinate, Saxony-Anhalt, Schleswig-Holstein and Thuringia. Additional, possibly compensatory, inpatient care was found for all city states (Hamburg, Bremen and Berlin) and Baden-Wuerttemberg. In federal states with a relative inpatient undertreatment and/or high inpatient hospital case numbers, there was often a lower availability of specialized epilepsy centers, specialized outpatient clinics and epilepsy outpatient clinics.
Conclusion: In Germany there are state-specific differences in the structure of care, with higher inpatient hospital care in the “new states” and Saarland. In addition, there were federal states with disproportionately higher treatment of patients not registered in this federal state. A potential influencing factor may be the availability of centers with specialized treatment for epilepsy patients.
Der Status epilepticus (SE) stellt eine schwerwiegende akute Erkrankung dar, die eine frühzeitige und gezielte Therapie erfordert. Insbesondere der refraktäre SE (RSE) sowie der superrefraktäre SE (SRSE) sind bereits bei jungen Menschen eine interdisziplinäre therapeutische Herausforderung. Bei Patienten in höherem Lebensalter sind hierbei weitere relevante Aspekte zu beachten, die sich einerseits aufgrund einer abweichenden Pharmakokinetik und -dynamik ergeben, andererseits aber auch aus Komorbiditäten, Polypharmazie und möglichen medizinischen Therapielimitationen bzw. Patientenpräferenzen resultieren. Ziel dieses Artikels ist es, diese besonderen Aspekte im Rahmen der SE-Versorgung älterer Menschen aufzuarbeiten und potenzielle Therapiestrategien jenseits der Leitlinie aufzuzeigen. Insbesondere wird hierbei auf alternative Applikationswege und mögliche konservative Eskalationsformen der Therapie eingegangen, die v. a. bei relevant vorerkrankten Patienten von Bedeutung sind, bei denen eine intensivmedizinische Behandlung die ohnehin schon hohe Mortalität des SE im gehobenen Alter weiter erhöhen würde. Mit unterschiedlichen parenteralen Applikationsformen von Benzodiazepinen im SE sowie dem mittlerweile gut beschriebenen Einsatz weiterer Antikonvulsiva wie Brivaracetam, Perampanel, Stiripentol, Topiramat und Zonisamid in RSE und SRSE stehen auch für diese vulnerable Patientengruppe adäquate Therapieoptionen zur Verfügung. Nichtsdestotrotz sollte in der Therapie des SE im gehobenen Alter insbesondere in Anbetracht der per se hohen Mortalität verstärkt auf Patientenpräferenzen und medizinethische Aspekte geachtet werden.
The developmental and epileptic encephalopathies encompass a group of rare syndromes characterised by severe drug-resistant epilepsy with onset in childhood and significant neurodevelopmental comorbidities. The latter include intellectual disability, developmental delay, behavioural problems including attention-deficit hyperactivity disorder and autism spectrum disorder, psychiatric problems including anxiety and depression, speech impairment and sleep problems. Classical examples of developmental and epileptic encephalopathies include Dravet syndrome, Lennox–Gastaut syndrome and tuberous sclerosis complex. The mainstay of treatment is with multiple anti-seizure medications (ASMs); however, the ASMs themselves can be associated with psychobehavioural adverse events, and effects (negative or positive) on cognition and sleep. We have performed a targeted literature review of ASMs commonly used in the treatment of developmental and epileptic encephalopathies to discuss the latest evidence on their effects on behaviour, mood, cognition, sedation and sleep. The ASMs include valproate (VPA), clobazam, topiramate (TPM), cannabidiol (CBD), fenfluramine (FFA), levetiracetam (LEV), brivaracetam (BRV), zonisamide (ZNS), perampanel (PER), ethosuximide, stiripentol, lamotrigine (LTG), rufinamide, vigabatrin, lacosamide (LCM) and everolimus. Bromide, felbamate and other sodium channel ASMs are discussed briefly. Overall, the current evidence suggest that LEV, PER and to a lesser extent BRV are associated with psychobehavioural adverse events including aggressiveness and irritability; TPM and to a lesser extent ZNS are associated with language impairment and cognitive dulling/memory problems. Patients with a history of behavioural and psychiatric comorbidities may be more at risk of developing psychobehavioural adverse events. Topiramate and ZNS may be associated with negative effects in some aspects of cognition; CBD, FFA, LEV, BRV and LTG may have some positive effects, while the remaining ASMs do not appear to have a detrimental effect. All the ASMs are associated with sedation to a certain extent, which is pronounced during uptitration. Cannabidiol, PER and pregabalin may be associated with improvements in sleep, LTG is associated with insomnia, while VPA, TPM, LEV, ZNS and LCM do not appear to have detrimental effects. There was variability in the extent of evidence for each ASM: for many first-generation and some second-generation ASMs, there is scant documented evidence; however, their extensive use suggests favourable tolerability and safety (e.g. VPA); second-generation and some third-generation ASMs tend to have the most robust evidence documented over several years of use (TPM, LEV, PER, ZNS, BRV), while evidence is still being generated for newer ASMs such as CBD and FFA. Finally, we discuss how a variety of factors can affect mood, behaviour and cognition, and untangling the associations between the effects of the underlying syndrome and those of the ASMs can be challenging. In particular, there is enormous heterogeneity in cognitive, behavioural and developmental impairments that is complex and can change naturally over time; there is a lack of standardised instruments for evaluating these outcomes in developmental and epileptic encephalopathies, with a reliance on subjective evaluations by proxy (caregivers); and treatment regimes are complex involving multiple ASMs as well as other drugs.
Eine barrierefreie Teilnahme am alltäglichen Leben stellt für Menschen mit aktiver Epilepsie häufig eine Herausforderung dar. Epileptische Anfälle können in Kindergarten, Schule und am Arbeitsplatz sowie im häuslichen Umfeld Unsicherheit und Überforderung hervorrufen. Individuell erstellte Pläne für Betreuende, Angehörige, Aufsichtspersonen und den Rettungsdienst sollen im Falle eines akuten Anfalls geeignete Handlungsanweisungen geben. Bisher gibt es hierfür im deutschsprachigen Raum keine standardisierten Vorlagen. Mit den Handlungsplänen bei epileptischen Anfällen für Laien (HEAL) bzw. Therapeuten (HEAT) werden hier 2 Formulare vorgestellt, die zum einen eine standardisierte Grundlage bieten und andererseits leicht auf den individuellen Bedarf angepasst werden können.
Eine barrierefreie Teilnahme am alltäglichen Leben stellt für Menschen mit aktiver Epilepsie häufig eine Herausforderung dar. Epileptische Anfälle können in Kindergarten, Schule und am Arbeitsplatz sowie im häuslichen Umfeld Unsicherheit und Überforderung hervorrufen. Individuell erstellte Pläne für Betreuende, Angehörige, Aufsichtspersonen und den Rettungsdienst sollen im Falle eines akuten Anfalls geeignete Handlungsanweisungen geben. Bisher gibt es hierfür im deutschsprachigen Raum keine standardisierten Vorlagen. Mit den Handlungsplänen bei epileptischen Anfällen für Laien (HEAL) bzw. Therapeuten (HEAT) werden hier 2 Formulare vorgestellt, die zum einen eine standardisierte Grundlage bieten und andererseits leicht auf den individuellen Bedarf angepasst werden können.
Tuberous sclerosis complex (TSC) is a rare genetic disease that is, besides cutaneous and visceral organ manifestations, typically associated with a severe, usually drug refractory epilepsy at a very early stage of the disease. Due to its direct effect on the mTOR signaling pathway dysregulated by TSC and its synergistic effects on other organ manifestations, the rapamycin derivative everolimus (EVE) is increasingly being used. The aim of this systematic review is to evaluate the efficacy, safety and tolerability of EVE in patients with TSC-associated, refractory epilepsy.
The hydrothermal vent tubeworm Riftia pachyptila hosts a single 16S rRNA phylotype of intracellular sulfur-oxidizing symbionts, which vary considerably in cell morphology and exhibit a remarkable degree of physiological diversity and redundancy, even in the same host. To elucidate whether multiple metabolic routes are employed in the same cells or rather in distinct symbiont subpopulations, we enriched symbionts according to cell size by density gradient centrifugation. Metaproteomic analysis, microscopy, and flow cytometry strongly suggest that Riftia symbiont cells of different sizes represent metabolically dissimilar stages of a physiological differentiation process: While small symbionts actively divide and may establish cellular symbiont-host interaction, large symbionts apparently do not divide, but still replicate DNA, leading to DNA endoreduplication. Moreover, in large symbionts, carbon fixation and biomass production seem to be metabolic priorities. We propose that this division of labor between smaller and larger symbionts benefits the productivity of the symbiosis as a whole.
We investigate the possible formation of a Bose-Einstein condensed phase of pions in the early Universe at nonvanishing values of lepton flavor asymmetries. A hadron resonance gas model with pion interactions, based on first-principle lattice QCD simulations at nonzero isospin density, is used to evaluate cosmic trajectories at various values of electron, muon, and tau lepton asymmetries that satisfy the available constraints on the total lepton asymmetry. The cosmic trajectory can pass through the pion condensed phase if the combined electron and muon asymmetry is sufficiently large: |le+lμ|≳0.1, with little sensitivity to the difference le−lμ between the individual flavor asymmetries. Future constraints on the values of the individual lepton flavor asymmetries will thus be able to either confirm or rule out the condensation of pions during the cosmic QCD epoch. We demonstrate that the pion condensed phase leaves an imprint both on the spectrum of primordial gravitational waves and on the mass distribution of primordial black holes at the QCD scale, e.g., the black hole binary of recent LIGO event GW190521 can be formed in that phase.
Hintergrund: Die chirurgische Facharztweiterbildung erfordert neben dem Erlernen theoretischen Wissens ebenfalls den Erwerb praktisch-chirurgischer Kompetenzen. Eine Alternative zur Aus- und Weiterbildung am Patienten stellen simulationsbasierte Lehrkonzepte dar. Ziel der vorliegenden Studie ist die Analyse der Verteilung und des Einsatzes chirurgischer Simulatoren in deutschen Kliniken.
Methoden: Die Datenanalyse erfolgte auf Basis eines individuellen Onlinefragebogens mit insgesamt 19 standardisierten Fragen. Dieser wurde über die E‑Mail-Verteiler der deutschen chirurgischen Fachgesellschaften an die leitenden chirurgischen Klinikärzte versendet.
Ergebnisse: Insgesamt 267 vollständige Antwortdatensätze wurden analysiert (Rücklaufquote 12,0 %). 84,0 % der Teilnehmer gaben ihre Tätigkeit an einem Lehrkrankenhaus an. Zum Zeitpunkt der Untersuchung waren 143 chirurgische Simulatoren an 35,0 % der in die Auswertung eingeschlossenen Kliniken vorhanden. Regional zeigten sich deutliche Unterschiede zwischen den einzelnen Bundesländern. 21,1 % der Teilnehmer, an deren Klinik kein Simulator zur Verfügung steht, planten eine Neubeschaffung. Studierende (41,1 %) und Ärzte in Weiterbildung (ÄiW, 32,5 %) nutzten das Simulationstraining am häufigsten. Eine Integration in die chirurgische Weiterbildung bestand zu 81,8 % nicht. 94,0 % der beteiligten Kliniken zeigten Interesse an einer zukünftigen Integration in die chirurgische Facharztweiterbildung.
Schlussfolgerung: Die vorliegenden Ergebnisse bestätigen die besondere Bedeutung des simulationsbasierten Trainings für die chirurgische Weiterbildung an deutschen Kliniken. Gleichzeitig bestehen deutliche Informationsdefizite über das Nutzungsverhalten sowie eine defizitär empfundene Integration des Simulationstrainings in die chirurgische Weiterbildung.
Thermally stable and highly conductive SAMs on Ag substrate — the impact of the anchoring group
(2021)
Self-assembled monolayers (SAMs) on metal substrates are an important part of modern interfacial chemistry and nanotechnology. The robustness of SAMs strongly depends on their thermal stability, which, together with electric conductivity, crucial for their applications in molecular/organic electronics. In this context, using a multidisciplinary approach, the structure, stability, and conductivity properties of conjugated aromatic SAMs featuring the naphthalene backbone and S, Se, or COO group, mediating bonding to the Ag substrate are addressed. Whereas thermal stability of these SAMs exhibits a strong dependence on anchoring group, their conductivity is similar, which is rationalized by tentative model considering redistribution of charge density along the molecular framework. The thermal stability of model naphthalenethiol SAM, emphasized by desorption energy of ≈1.69 eV, is better than that of typical N-heterocyclic carbene (NHC) monolayers considered currently as the most stable SAMs on metal substrates. However, in contrast to NHC SAMs, which are highly insulating, the naphtalene-based SAM, with S, Se or COO anchoring groups, are highly conductive, even in comparison with analogous oligophenyl SAMs (by a factor of 10). A unique combination of the ultimate thermal stability and superior conductivity for the naphthalenethiol SAM on Ag makes it highly attractive for applications.
The Born cross sections and effective form factors for process 𝑒+𝑒−→Ξ−¯Ξ+ are measured at eight center-of-mass energies between 2.644 and 3.080 GeV, using a total integrated luminosity of 363.9 pb−1 𝑒+𝑒− collision data collected with the BESIII detector at BEPCII. After performing a fit to the Born cross section of 𝑒+𝑒−→Ξ−¯Ξ+, no significant threshold effect is observed.
The present study aims to report the currently available epidemiology of focal onset seizures in children aged >1 month to 4 years with the help of a literature review. The terms ‘seizure*’ OR ‘epilepsy’ combined with pediatric and epidemiology terms were used to search Embase, PubMed, and Web of Science up to November 16, 2021. Due to the scarcity of epidemiology data on focal onset seizures, the incidence and prevalence were estimated using the proportion of focal onset seizures in epilepsy patients from the most recently published articles. The estimated annual incidence per 100,000 children of focal onset seizures in children of 0–4 years of age ranged from 25.1 (95 % confidence interval [CI] 18.9–32.7) in the United Kingdom to 111.8 in the United States. The estimated period prevalence of focal onset seizures in children 0–4 years of age ranged from 0.15 % (99 % CI 0.13–0.18) in Canada to 0.61 % in the United States. Neurodevelopmental outcomes and psychiatric disorders were the most commonly reported comorbidities in children with epilepsy of age 0–4 years. Presence of focal onset seizures in children with different epilepsy syndromes needs to be thoroughly considered in the treatment planning of this population of interest.
Background: Multiple studies have focused on medical and pharmacological treatments and outcome predictors of patients with status epilepticus (SE). However, a sufficient understanding of recurrent episodes of SE is lacking. Therefore, we reviewed recurrent SE episodes to investigate their clinical characteristics and outcomes in patients with relapses.
Methods: In this retrospective, multicenter study, we reviewed recurrent SE patient data covering 2011 to 2017 from the university hospitals of Frankfurt and Marburg, Germany. Clinical characteristics and outcome variables were compared among the first and subsequent SE episodes using a standardized form for data collection.
Results: We identified 120 recurrent SE episodes in 80 patients (10.2% of all 1177 episodes). The mean age at the first SE episode was 62.2 years (median 66.5; SD 19.3; range 21–91), and 42 of these patients were male (52.5%). A mean of 262.4 days passed between the first and the second episode. Tonic–clonic seizure semiology and a cerebrovascular disease etiology were predominant in initial and recurrent episodes. After subsequent episodes, patients showed increased disability as indicated by the modified Rankin Scale (mRS), and 9 out of 80 patients died during the second episode (11.3%). Increases in refractory and super-refractory SE (RSE and SRSE, respectively) were noted during the second episode, and the occurrence of a non-refractory SE (NRSE) during the first SE episode did not necessarily provide a protective marker for subsequent non-refractory episodes. An increase in the use of intravenous-available anti-seizure medication (ASM) was observed in the treatment of SE patients. Patients were discharged from hospital with a mean of 2.8 ± 1.0 ASMs after the second SE episode and 2.1 ± 1.2 ASMs after the first episode. Levetiracetam was the most common ASM used before admission and on discharge for SE patients.
Conclusions: This retrospective, multicenter study used the mRS to demonstrate worsened outcomes of patients at consecutive SE episodes. ASM accumulations after subsequent SE episodes were registered over the study period. The study results underline the necessity for improved clinical follow-ups and outpatient care to reduce the health care burden from recurrent SE episodes.
Highlights
• German patients with LGS identified using most specific algorithm to date.
• Prevalence of probable LGS with epilepsy diagnosis before age 6 was 6.5 per 100,000.
• High healthcare costs of €22,787 PPY; mostly due to inpatient and home nursing care.
• Costs were greater in patients prescribed rescue medications.
• Over 10 years, LGS patients had significant mortality vs. controls (2.88 vs. 0.01%).
Abstract
Objective: This retrospective study examined patients with probable Lennox-Gastaut syndrome (LGS) identified from German healthcare data.
Methods: This 10-year study (2007–2016) assessed healthcare insurance claims information from the Vilua Healthcare research database. A selection algorithm considering diagnoses and drug prescriptions identified patients with probable LGS. To increase the sensitivity of the identification algorithm, two populations were defined: all patients with probable LGS (broadly defined) and only those with a documented epilepsy diagnosis before 6 years of age (narrowly defined). This specific criterion was used as LGS typically has a peak seizure onset between age 3 and 5 years. Primary analyses were prevalence and demographics; secondary analyses included healthcare costs, hospitalization rate and length of stay (LOS), medication use, and mortality.
Results: In the final year of the study, 545 patients with broadly defined probable LGS (mean [range] age: 31.4 [2–89] years; male: 53%) were identified. Using the narrowly defined probable LGS definition, the number of patients was reduced to 102 (mean [range] age: 7.4 [2–14] years; male: 52%). Prevalence of broadly defined and narrowly defined probable LGS was 39.2 and 6.5 per 100,000 people. During the 10-year study, 208 patients with narrowly defined probable LGS were identified and followed up for 1379 patient-years. The mean annual cost of healthcare was €22,787 per patient-year (PPY); greatest costs were attributable to inpatient care (33%), home nursing care (13%), and medication (10%). Mean annual healthcare costs were significantly greater for those with prescribed rescue medication (45% of patient-years) versus those without (€33,872 vs. €13,785 PPY, p < 0.001). Mean (standard deviation [SD]) annual hospitalization rate was 1.6 (2.0) PPY with mean (SD) annual LOS of 22.7 (46.0) days. Annual hospitalization rate was significantly greater in those who were prescribed rescue medication versus those who were not (2.2 [2.3] vs. 1.1 [1.6] PPY, p < 0.001). The mean (SD) number of different medications prescribed was 11.3 (7.3) PPY and 33.8 (17.0) over the entire observable time per patient (OET); antiepileptic drugs only accounted for 2.1 (1.1) of the medications prescribed PPY and 3.8 (2.0) OET. Over the 10-year study period, mortality in patients with narrowly defined probable LGS was significantly higher than the matched control population (six events [2.88%] vs. one event [0.01%], p < 0.001).
Conclusion: Annual healthcare costs incurred by patients with probable LGS in Germany were substantial, and mostly attributable to inpatient care, home nursing care, and medication. Patients prescribed with rescue medication incurred significantly greater costs than those who were not. Patients with narrowly defined probable LGS had a higher mortality rate versus control populations.
Highlights
• Prevalence of probable DS identified from German healthcare data: 4.7 per 100,000.
• Healthcare costs: €11,048 per patient-year, mostly inpatient care 47%, medication 26%.
• Costs and hospitalizations greater in patients with rescue medication than without.
• Mean (SD) of 5.0 (2.5) different ASMs prescribed per patient over study period.
• Patients with probable DS had significantly higher mortality risk vs. controls (11.88% vs. 1.19%).
Abstract
Objective: Ten-year retrospective study to assess burden of illness in patients with probable Dravet syndrome (DS) identified from German healthcare data.
Methods: In the absence of an International Classification of Diseases code, patients with probable DS were identified using a selection algorithm considering diagnoses and drug prescriptions. Primary analyses were prevalence and demographics; secondary analyses included healthcare costs, annual hospitalization rate (AHR) and length of stay (LOS), medication use, and mortality.
Results: In the final study year, 64 patients with probable DS (mean [range] age: 33.2 [3–82] years; male: 48%) were identified. Prevalence: 4.7 per 100,000 people. During the study, 160 patients with probable DS were identified and followed up for 1,261 patient-years. Mean cost of healthcare was €11,048 per patient-year (PPY), mostly attributable to inpatient care (47%), medication (26%), and services and devices (19%). Annual healthcare costs were significantly greater for those with prescribed rescue medication (15% of patient-years) vs. without (€16,123 vs. €10,125 PPY, p < 0.001). Mean (standard deviation [SD]) AHR and LOS were 1.1 (1.7) and 17.5 (33.5) days PPY. AHR was significantly greater in patients with prescribed rescue medication vs. without (1.6 [2.0] vs. 1.0 [1.6] PPY, p < 0.001). Mean (SD) number of antiseizure medications prescribed was 2.6 (1.2) PPY and 5.0 (2.5) over the entire observable time for each patient. Mortality rate was significantly higher for probable DS vs. matched controls (11.88% [19 events] vs. 1.19% [172 events], p < 0.001).
Conclusion: Probable DS is associated with substantial healthcare costs in Germany.
An important goal is to identify the direct activation domain (AD)-interacting components of the transcriptional machinery within the context of native complexes. Toward this end, we first demonstrate that the multisubunit TFIID, SAGA, mediator, and Swi/Snf coactivator complexes from transcriptionally competent whole-cell yeast extracts were all capable of specifically interacting with the prototypic acidic ADs of Gal4 and VP16. We then used hexahistidine tags as genetically introduced activation domain-localized cross-linking receptors. In combination with immunological reagents against all subunits of TFIID and SAGA, we systematically identified the direct AD-interacting subunits within the AD-TFIID and AD-SAGA coactivator complexes enriched from whole-cell extracts and confirmed these results using purified TFIID and partially purified SAGA. Both ADs directly cross-linked to TBP and to a subset of TFIID and SAGA subunits that carry histone-fold motifs.
Mnemonic but not contextual feedback signals defy dedifferentiation in the aging early visual cortex
(2024)
Perception is an intricate interplay between feedforward visual input and internally generated feedback signals that comprise concurrent contextual and time-distant mnemonic (episodic and semantic) information. Yet, an unresolved question is how the composition of feedback signals changes across the lifespan and to what extent feedback signals undergo age-related dedifferentiation, that is, a decline in neural specificity. Previous research on this topic has focused on feedforward perceptual representation and episodic memory reinstatement, suggesting reduced fidelity of neural representations at the item and category levels. In this fMRI study, we combined an occlusion paradigm that filters feedforward input to the visual cortex and multivariate analysis techniques to investigate the information content in cortical feedback, focusing on age-related differences in its composition. We further asked to what extent differentiation in feedback signals (in the occluded region) is correlated to differentiation in feedforward signals. Comparing younger (18–30 years) and older female and male adults (65–75 years), we found that contextual but not mnemonic feedback was prone to age-related dedifferentiation. Semantic feedback signals were even better differentiated in older adults, highlighting the growing importance of generalized knowledge across ages. We also found that differentiation in feedforward signals was correlated with differentiation in episodic but not semantic feedback signals. Our results provide evidence for age-related adjustments in the composition of feedback signals and underscore the importance of examining dedifferentiation in aging for both feedforward and feedback processing.
Highlights
• Short- and long-delay memory consolidation is less robust in children than in young adults.
• Short-delay brain profile comprised of hippocampal, cerebellar, and neocortical brain regions.
• Long-delay brain profile comprised of neocortical and selected hippocampal brain regions.
• Brain profiles differ between children and young adults.
Abstract
From early to middle childhood, brain regions that underlie memory consolidation undergo profound maturational changes. However, there is little empirical investigation that directly relates age-related differences in brain structural measures to memory consolidation processes. The present study examined memory consolidation of intentionally studied object-location associations after one night of sleep (short delay) and after two weeks (long delay) in normally developing 5-to-7-year-old children (n = 50) and young adults (n = 39). Behavioural differences in memory retention rate were related to structural brain measures. Our results showed that children, in comparison to young adults, retained correctly learnt object-location associations less robustly over short and long delay. Moreover, using partial least squares correlation method, a unique multivariate profile comprised of specific neocortical (prefrontal, parietal, and occipital), cerebellar, and hippocampal head and subfield structures in the body was found to be associated with variation in short-delay memory retention. A different multivariate profile comprised of a reduced set of brain structures, mainly consisting of neocortical (prefrontal, parietal, and occipital), hippocampal head, and selective hippocampal subfield structures (CA1–2 and subiculum) was associated with variation in long-delay memory retention. Taken together, the results suggest that multivariate structural pattern of unique sets of brain regions are related to variations in short- and long-delay memory consolidation across children and young adults.
Childhood is a period when memory consolidation and knowledge base undergo rapid changes. The present study examined short-delay (overnight) and long-delay (after a 2-week period) consolidation of new information either congruent or incongruent with prior knowledge in typically developing 6- to 8-year-old children (n = 32), 9- to 11-year-old children (n = 33), and 18- to 30-year-old young adults (YA; n = 39). Both memory accessibility (cued recall of objects) and precision (precision of object placement) of initially well-learned object–scene pairs were measured. Our results showed that overnight, memory accessibility declined similarly in all age groups; memory precision improved more in younger children (YC) compared to older children (OC) and even declined in YA. After a 2-week period, both memory accessibility and precision became worse. Specifically, while age groups showed similar decline in memory accessibility, precision decline was less in YC than in OC and YA. The accessibility and precision of congruent and incongruent information changed similarly with consolidation in all age groups. Taken together, our results showed that, for initially well-learned information, YC have robust memory consolidation, despite their overall lower mnemonic performance compared to OC and YA, which is potentially crucial for stable and precise knowledge accumulation early on in development.
Preparing auditory task switching in a task with overlapping and non-overlapping response sets
(2023)
We used a variant of cued auditory task switching to investigate task preparation and its relation to response-set overlap. Previous studies found increased interference with overlapping response sets across tasks relative to non-overlapping motor response sets. In the present experiments, participants classified either pitch or loudness of a simple tone as low or high, hence, both tasks were constructed around common underlying integrated semantic categories ranging from low to high. Manual responses overlapped in both category and modality for both tasks in Experiment 1A, whereas each task was related to a specific response category and response modality (manual vs. vocal) in Experiment 1B. Focusing on the manual responses in both experiments, the data showed that non-overlapping response sets (Experiment 1B) resulted in a decreased congruency effect, suggesting reduced response-based crosstalk and thus better task shielding, but at the same time switch costs were increased, suggesting less efficient switching between task sets. Moreover, varying preparation time (cue-stimulus interval, CSI) showed that long CSI led to better performance overall. Our results thus suggest that when non-overlapping response sets share common semantic categories across tasks, there is no general benefit over overlapping response sets.
The role of response set overlap for flexibility and cognitive control in auditory multitasking
(2022)
Highlights
• We introduced a new variant of auditory task-switching.
• Motor response set overlap was varied systematically across two experiments.
• Switch costs and congruency effects were similar for manual and vocal responses.
• Switch costs were not reduced with reduced motor response set overlap.
• We dissociated effects of motor response modality from motor response set overlap.
Abstract
We developed a new variant of auditory task-switching in order to systematically investigate shifting and cognitive control in auditory task-switching and their relation to motor response overlap in a comprehensive way. In two experiments, participants classified either pitch or loudness of a simple tone as either low or high, hence, both tasks were constructed around a common underlying dimension ranging from low to high. In Experiment 1, response sets overlapped in both category and motor modality (both manual), whereas each task was related to a specific response category and motor response modality (manual vs. vocal) in Experiment 2. The data revealed reliable switch costs that were, contrary to our expectations, not reduced with reduced response set overlap. In addition, we found reliable congruency effects and their sequential modulation in both experiments with manual as well as vocal responses, and in the absence of competing motor activation (i.e., without motor response overlap). Congruency effects after auditory task switches were smaller when response sets did not overlap. Our data thus provides an important empirical generalization of known effects to auditory stimuli as well as with both manual and vocal responses. In addition, we demonstrated that reduced congruency effects after switches for non-overlapping response sets were due to the extent of overlap between different response sets in task-switching.
The Board of Directors of the German Society of Epileptology and the committee on epilepsy and syncope of the German Society of Neurology have reviewed the current data on vaccination to prevent coronavirus disease 2019 (COVID-19) and vaccination prioritization in people with epilepsy and provide a summary and recommendations.
100 Jahre Dieter Janz
(2020)
The 20 April 2020 marks the centenary of Dieter Janz’s birth. This issue of Zeitschrift für Epileptologie is published in his honor with the aim of tracing the work of Dieter Janz over the last five decades and summarizing new findings on the Janz syndrome (Juvenile Myoclonic Epilepsy), which is named after him.
The paper presents the findings of two recent books on the financial history of the Frankfurt School: Jeanette Erazo-Heufelder, Der argentinische Krösus: Kleine Wirtschaftsgeschichte der Frankfurter Schule, 2017, and Bertus Mulder, Sophie Louisa Kwaak und das Kapital der Unternehmerfamilie Weil. Ein Beitrag zur Wirtschaftsgeschichte der Frankfurter Schule, 2021 (Dutch original 2015). In contrast to the “court histories” of the school, the two authors tell the story of the money that brought the school to life and secured its existence throughout a turbulent period of history. At the center of the books are individuals who have been sidelined until now or even completely ignored by the literature on the Frankfurt School: on the one hand, Felix Weil, who founded and financed the Institute of Social Research and, on the other hand, Erich A. Nadel and Sophie L. Kwaak, two employees of the holding company who managed the accounts of the Weil family and the Institute’s foundations and were responsible for protecting the assets from being seized by Nazis. The books’ thick descriptions induced the author of the present paper to consider an alternative perspective on the Frankfurt School by contemplating Max Horkheimer and Friedrich Pollock as playing confidential games with Weil and others.
Hintergrund: Mit der im Jahr 2020 aktualisierten AWMF-Leitlinie zur Versorgung mit einem Cochleaimplantat (CI) wurde erstmals der gesamte Prozess einer CI-Versorgung definiert. In der vorliegenden Studie wurden die Machbarkeit und die Ergebnisse einer sehr frühen Rehabilitationsmaßnahme (Reha) untersucht.
Methodik: Es wurden 54 Patienten in die Interventionsgruppe (IG) eingeschlossen, bei der die Reha innerhalb von 14 (maximal 28) Tagen nach der Implantation eingeleitet wurde. In eine Kontrollgruppe (KG, n = 21) wurden Patienten mit deutlich längerer Wartezeit eingeschlossen. Neben dem Beginn und der Dauer der Reha wurde das mit CI erreichte Sprachverstehen zu verschiedenen Zeitpunkten innerhalb von 12 Monaten erfasst. Zusätzlich wurde mit Fragebögen der Aufwand der Anpassung des CI-Prozessors und die Zufriedenheit der Patienten mit dem Ergebnis sowie dem Zeitpunkt des Beginns der Reha ermittelt.
Ergebnisse: Die Wartezeit zwischen Implantation und Beginn der Reha lag in der IG bei 14 Tagen und in der KG bei 106 Tagen (Mediane). Es konnten 92,6 % der Patienten der IG die Reha innerhalb von 14 Tagen antreten. Der Effekt der Reha lag in der IG bei 35 und in der KG bei 25 Prozentpunkten (Freiburger Einsilbertest). Nach 6 und 12 Monaten (M) CI-Nutzung zeigten beide Gruppen sowohl in der Testbedingung in Ruhe (IG/KG 6M: 70 %/70 %; 12M: 70 %/60 %, Freiburger Einsilbertest) als auch im Störgeräusch (IG/KG 6M: −1,1 dB SNR/–0,85 dB SNR; 12M: −0,65 dB SNR/+0,3 dB SNR, Oldenburger Satztest) vergleichbare Ergebnisse. Die mittels des Fragebogens Speech, Spatial and Qualities of Hearing Scale (SSQ) erfassten Ergebnisse für die Einschätzung der Hörqualität zeigten nach 6 Monaten eine bessere Bewertung in der IG, die sich nach 12 Monaten an die Ergebnisse der KG anglich. Die IG war mit dem Zeitpunkt des Beginns der Reha deutlich zufriedener als die KG. Alle anderen aus Fragebögen ermittelten Daten zeigten keine Unterschiede zwischen den beiden Gruppen.
Schlussfolgerung: Der sehr frühe Beginn einer stationären Reha nach Cochleaimplantation ist erfolgreich umsetzbar. Die Reha konnte innerhalb von 7 Wochen nach der Implantation abgeschlossen werden. Der Vergleich der Ergebnisse der Tests des Sprachverstehens vor und nach der Reha zeigte eine deutliche Steigerung. Somit ist ein deutlicher Reha-Effekt nachweisbar. Die Aufnahme der CI-Rehabilitation in den Katalog der Anschlussheilbehandlungen ist somit wissenschaftlich begründet und damit dringend zu empfehlen.
Background: The Association of the Scientific Medical Societies in Germany (AWMF) clinical practice guideline on cochlear implant (CI) treatment, which was updated in 2020, defined the entire process of CI care for the first time. In the present study, the feasibility and results of very early rehabilitation were examined.
Materials and methods: The intervention group (IG) comprised 54 patients in whom rehabilitation was initiated within 14 (maximally 28) days after implantation. Patients with a significantly longer waiting time were included in the control group (CG, n = 21). In addition to the start and duration of rehabilitation, the speech intelligibility achieved with CI was recorded at different timepoints within a 12-month period. In addition, questionnaires were used to assess the effort of fitting the CI processor and the patients’ satisfaction with the outcome as well as the timing of the start of rehabilitation.
Results: Median waiting time between implantation and start of rehabilitation was 14 days in the IG and 106 days in the CG; 92.6% of IG patients were able to start rehabilitation within 14 days. The effect of rehabilitation in the IG was 35 and in the CG 25 percentage points (Freiburg monosyllabic test). After 6 and 12 months of CI use, both groups showed comparable results in the test condition in quiet (IG/CG 6 months: 70%/70%; 12 months: 70%/60%, Freiburg monosyllabic test) and in noise (IG/CG 6 months: −1.1 dB SNR/–0.85 dB SNR; 12 months: −0.65 dB SNR/+0.3 dB SNR, Oldenburg sentence test). Hearing quality assessment scores collected by SSQ (Speech, Spatial and Qualities of Hearing Scale) questionnaire showed better scores in the IG at 6 months, which converged to CG scores at 12 months. The IG was significantly more satisfied with the timing of the start of rehab than the CG. All other data obtained from questionnaires showed no differences between the two groups.
Conclusion: A very early start of inpatient rehabilitation after cochlear implantation was successfully implemented. The rehabilitation was completed within 7 weeks of CI surgery. Comparison of speech recognition test results before and after rehabilitation showed a significant improvement. A clear rehabilitation effect can therefore be demonstrated. Inclusion of CI rehabilitation in the German catalog of follow-up treatments is thus scientifically justified and therefore strongly recommended.
Owing to their morphological complexity and dense network connections, neurons modify their proteomes locally, using mRNAs and ribosomes present in the neuropil (tissue enriched for dendrites and axons). Although ribosome biogenesis largely takes place in the nucleus and perinuclear region, neuronal ribosomal protein (RP) mRNAs have been frequently detected remotely, in dendrites and axons. Here, using imaging and ribosome profiling, we directly detected the RP mRNAs and their translation in the neuropil. Combining brief metabolic labeling with mass spectrometry, we found that a group of RPs rapidly associated with translating ribosomes in the cytoplasm and that this incorporation was independent of canonical ribosome biogenesis. Moreover, the incorporation probability of some RPs was regulated by location (neurites vs. cell bodies) and changes in the cellular environment (following oxidative stress). Our results suggest new mechanisms for the local activation, repair and/or specialization of the translational machinery within neuronal processes, potentially allowing neuronal synapses a rapid means to regulate local protein synthesis.
Protein turnover, the net result of protein synthesis and degradation, enables cells to remodel their proteomes in response to internal and external cues. Previously, we analyzed protein turnover rates in cultured brain cells under basal neuronal activity and found that protein turnover is influenced by subcellular localization, protein function, complex association, cell type of origin, and by the cellular environment (Dörrbaum et al., 2018). Here, we advanced our experimental approach to quantify changes in protein synthesis and degradation, as well as the resulting changes in protein turnover or abundance in rat primary hippocampal cultures during homeostatic scaling. Our data demonstrate that a large fraction of the neuronal proteome shows changes in protein synthesis and/or degradation during homeostatic up- and down-scaling. More than half of the quantified synaptic proteins were regulated, including pre- as well as postsynaptic proteins with diverse molecular functions.
The genus Legua Walker, 1870 comprises only two known species from Central America and Brazil, with a notable scarcity of collected specimens. Herein, we provide a new contribution to our knowledge of the distribution of Legua rosea Amédégnato and Poulain, 1986 (Romaleinae: Leguini), that has a restricted distribution in Brazil, based on entomological collection data and social media information. Our records emphasize the importance of natural history collections and new tools for biodiversity studies.
ZooBank registration. urn:lsid:zoobank.org:pub:17E0802B-A389-4983-AC74-21B51197F557
A new species of Paranthrene Hübner (Lepidoptera: Sesiidae) from the northern midwest United States
(2024)
A clearwing moth species, Paranthrene sogaardi Taft and Smith, 2024, new species, is described from Michigan and Minnesota. The recognition of this new species is based on a phylogeny estimated from mitochondrial cytochrome oxidase I and wingless DNA sequences of 25 specimens representing all Paranthrene Hübner species including individuals from various locations. Paranthrene sogaardi new species was monophyletic and differed from Paranthrene tabaniformis Rottenburg, 1775 by a mean of 7.6% COI pairwise “p” distance, coloration, and genitalic morphology.
ZooBank registration. urn:lsid:zoobank.org:pub:8B9ED6CE-4DEB-4CB2-9235-3CA593F4D9DB
Hurd (1952) separated Pepsis cerberus Lucas from P. elegans Lepeletier (Hymenoptera: Pompilidae: Pepsinae: Pepsini) based on external morphology and biogeography. Vardy (2005) synonymized the familiar and historically well-documented P. cerberus and P. elegans, combining these Nearctic taxa with several Neotropical variants in an extremely broad definition of P. menechma Lepeletier. In doing so, Vardy (2005) breached the principle of nomenclatural stability. He ignored the prevailing usage and clearly violated articles 23.2, 23.3 and 23.9.1.2 of the ICZN (1999). Morphological differences, ecological divergence, and narrow sympatric geographic distribution of P. cerberus and P. elegans contradict Vardy (2005) and justify full species status (Kurczewski 2023a). Furthermore, we propose the removal of the two species from the P. menechma list of synonyms and recommend full species reinstatement as Pepsis cerberus, restored status and Pepsis elegans, restored status. Pepsis menechma becomes a senior synonym of P. elegans. Morphometric re-examination and statistical analysis of P. cerberus and P. elegans structural features strongly support their reinstatement. Quantitative measurement of 10 parasitoid-related morphological characteristics of the females revealed the two species differ significantly in frons width/head width, head length/head width, vertex length/head width, vertex length/head length, flagellomere 1 length/flagellomere 1 width, forewing length/mesosoma width, and hind tibial inner spur length/hind basitarsus length. Pepsis cerberus and P. elegans females are structurally and statistically similar in gena-postgena corner radius, fore femur width/mesosoma width, and number of hind tibial serrations.
ZooBank registation. urn:lsid:zoobank.org:pub:D22EC64F-7C55-4071-9290-4661CA377B24
The geographic distributions of three large wasps, Sphecius speciosus (Drury), Stictia carolina Fabricius and Stizus brevipennis Walsh (Hymenoptera: Crabronidae), occurring in Arkansas are defined using museum specimens and three internet-based data platforms. The internet-based data platforms generally provided more county location records than museum records. Using data from internet sources for easily identified species can better serve to illustrate the known distributions for some species thus making for a powerful tool elucidating distributional patterns and conservation planning.
ZooBank registration. urn:lsid:zoobank.org:pub:DCAE9192-1765-40CD-952B-0A094F413991
Corrections and additions to the Hydnocerina (Coleoptera: Cleridae: Clerinae: Hydnocerini) of Mexico
(2024)
Corrections, additions and remarks are made with respect to the recent checklist of the Cleridae (Coleoptera) of Mexico (Araujo-Castillo et al. 2024). Current valid names, synonymies, clarifications of taxonomic problems, and omitted taxa are reviewed. This work is intended to serve as a supplement to the “Hydnocerinae” section of the checklist.
ZooBank registration. urn:lsid:zoobank.org:pub:EF3E45B5-6EA6-41AB-B92F-DB4ABF9D8215
The exclusively New World velvet ant genus Timulla Ashmead, 1899 (Hymenoptera: Mutillidae: Mutillinae: Trogaspidiini) contains 180 species and ten subspecies. Most of these species are known from a single sex, and the validity of the subspecies has not been evaluated since their original description in 1937 and 1938. The Timulla fauna of the United States of America includes thirty species and eight subspecies, and the fauna of Canada includes three species. The faunas of these two countries were critically studied with the following results. Out of the eight total subspecies, seven were found to be structurally identical to and sympatric with the nominate subspecies. The subspecific differences were limited to cuticle and/or setal coloration in males and intergrades between them were found in several cases. With the senior synonym listed first, seven subspecies-level synonymies are proposed, which include: Timulla barbigera (Bradley, 1916) = T. barbigera rohweri Mickel, 1937, new synonym; T. dubitata (Smith, 1855) = T. dubitata fugitiva Mickel, 1937, new synonym; T. hollensis (Melander, 1903) = T. hollensis melanderi Mickel, 1937, new synonym; T. ocellaria Mickel, 1937 = T. ocellaria rufidorsa Mickel, 1937, new synonym; T. suspensa (Gerstaecker, 1874) = T. suspensa jonesi Mickel, 1937, new synonym, = T. suspensa sonora Mickel, 1937, new synonym; T. vagans (Fabricius, 1798) = T. vagans rufinota Mickel, 1937, new synonym. The final remaining subspecies, Timulla navasota coahuila Krombein, 1951, is raised to a full species, Timulla coahuila Krombein, 1951, new status, based on its unique female morphology. Also, four new sex associations are proposed, which include: Timulla barbata (Fox, 1899) = T. wileyae Mickel, 1937, new synonym; T. euterpe (Blake, 1879) = T. compressicornis Mickel, 1937, new synonym; T. neobule Mickel, 1937 = T. nicholi Mickel, 1937, new synonym; T. subhyalina Mickel, 1937 = T. dubitatiformis Mickel, 1937, new synonym. The former species, T. dubitatiformis, which was previously known only from females, is here recognized as being a morphologically-conservative complex of species; its synonymy with T. subhyalina effectively associates the remaining male-based members of the Timulla ocellaria species-group with it as well, which includes Timulla hollensis (Melander, 1903), T. kansana Mickel, 1937, T. ocellaria Mickel, 1937, T. rufosignata (Bradley, 1916), T. sayi (Blake, 1871), T. subhyalina Mickel, 1937, and T. tolerata Mickel, 1937. Further, two species-level synonymies are proposed, which include: Timulla dubitata (Smith, 1855) = T. murcia Mickel, 1938, new synonym; T. vagans (Fabricius, 1798) = T. huntleyensis Mickel, 1937, new synonym. Finally, Timulla cyllene (Cameron, 1894) is newly recorded in the United States of America from the state of Arizona.
ZooBank registration. urn:lsid:zoobank.org:pub:891E0C92-B8BF-4487-84D4-42EB2254AF4A
Viruses that carry a positive-sense, single-stranded (+ssRNA) RNA translate their genomes soon after entering the host cell to produce viral proteins, with the exception of retroviruses. A distinguishing feature of retroviruses is reverse transcription, where the +ssRNA genome serves as a template to synthesize a double-stranded DNA copy that subsequently integrates into the host genome. As retroviral RNAs are produced by the host cell transcriptional machinery and are largely indistinguishable from cellular mRNAs, we investigated the potential of incoming retroviral genomes to directly express proteins. Here we show through multiple, complementary methods that retroviral genomes are translated after entry. Our findings challenge the notion that retroviruses require reverse transcription to produce viral proteins. Synthesis of retroviral proteins in the absence of productive infection has significant implications for basic retrovirology, immune responses and gene therapy applications.
We examined the feedback between the major protein degradation pathway, the ubiquitin-proteasome system (UPS), and protein synthesis in rat and mouse neurons. When protein degradation was inhibited, we observed a coordinate dramatic reduction in nascent protein synthesis in neuronal cell bodies and dendrites. The mechanism for translation inhibition involved the phosphorylation of eIF2α, surprisingly mediated by eIF2α kinase 1, or heme-regulated kinase inhibitor (HRI). Under basal conditions, neuronal expression of HRI is barely detectable. Following proteasome inhibition, HRI protein levels increase owing to stabilization of HRI and enhanced translation, likely via the increased availability of tRNAs for its rare codons. Once expressed, HRI is constitutively active in neurons because endogenous heme levels are so low; HRI activity results in eIF2α phosphorylation and the resulting inhibition of translation. These data demonstrate a novel role for neuronal HRI that senses and responds to compromised function of the proteasome to restore proteostasis.
The nine genera of Malagasy spittlebug are revised, with the addition of new characters, facilitating the identification of the species. Nesaulax Jacobi, 1917, is synonymized with Amberana Distant, 1908, leading to a new combination for Amberana vittipennis (Bergroth, 1894). A new endemic genus Soulierana Bucher & Bouteille gen. nov. is proposed for two species originally placed in Literna Stål, 1866, based on morphological characters of the head, tegmina and male genitalia. Also, three new species are described in this genus: Soulierana bigidea Bucher gen. et sp. nov., Soulierana claudinae Bouteille gen. et sp. nov. and Soulierana kelymena Le Cesne gen. et sp. nov. Pictures of species and drawings of the male genitalia for all genera, with the exception of Rhinaulax Amyot & Serville, 1843, Alluaudensia Lallemand, 1920 and Literna, are included. An identification key is available in both a dichotomous format and an interactive format (Xper3).
Systematics of the Sierra Nevada endemic earwig: Eulithinus analis (Forficulidae, Dermaptera)
(2024)
Since the description of Eulithinus analis (Rambur, 1838) the taxonomic position of this Sierra Nevada endemic earwig has been controversial. It has been subdivided in different taxa, assigned to various genera or transferred to different subfamilies. With the aim of clarifying its systematics, we performed a mitochondrial phylogeographic analysis using specimens from different localities of Sierra Nevada representing the diverse phenotypes treated as differentiated taxa until now, and a phylogenetic analysis including representatives of apparently distant, but morphologically close, relatives. The phylogenetic and phylogeographic results obtained using mitochondrial (cytb, cox1) and nuclear (ITS2) markers and the study of morphological characters, indicate that the Sierra Nevada Mountain Range harbors a single species of the genus Eulithinus. Based on these molecular data, the morphological characters used to date in the internal taxonomy of this group of earwigs, especially size and shape of the cerci, lack diagnostic validity and show a large inter- and intra-populational variability. These results imply the synonymy of Eulithinus montanus (Steinmann, 1981) with Eulithinus analis (Rambur, 1838) syn. nov. and the reconsideration of Eulithinus analis outside the subfamily Allodahliinae. We established the synonymy between Eulithinus analis (Rambur, 1838) and Forficula brevis Rambur, 1838 syn. nov., a name that must be removed from the synonymy of Forficula decipiens Gené, 1832.
Wir berichten über die Erfahrungen beim Aufbau einer Abteilung für die präoperative Eigenblutentnahme im Verantwortungsbereich des Institutes für Laboratoriumsmedizin der Städtischen Kliniken Frankfurt am Main-Höchst, einem Krankenhaus der Maximalversorgung mit 1150 Betten bzw. Tagesklinikplätzen. Die Herstellung von Eigenblutkonserven erfolgt nach § 13 des Arzneimittelgesetzes. Die Planung erfordert eine genaue Analyse des zu erwartenden Umfanges, der gegebenen Strukturen und betrieblichen Kapazitäten. Unsere Erfahrungen zeigen, daß mit der Entnahme von ca. 1200 autologen Blutkonserven pro Jahr und deren weiteren Bearbeitung eine Medizinisch-technische Assistentin ganztags und ein Arzt halbtags beschäftigt sind. Aus Gründen der Produktqualität und -Sicherheit sollte eine Trennung in die Komponenten Erythrozytenkonzentrat und Gefrorenes Frischplasma erfolgen und ein Qualitätssicherungssystem etabliert werden, das dem der Herstellung von homologen Blutkonserven entspricht. Dies bedeutet, bei jeder Entnahme die in den Richtlinien zur Blutgruppenbestimmung und Bluttransfusionen (Hämotherapie) in § 3.2.5 angegebenen Parameter zu testen (Glutamat-Pyruvattransaminase, Hepatitis B surfaceAntigen sowie Antikörper gegen Humanes Immundefizienz-Virus 1/2, Hepatitis-C-Virus und Treponema pallidum). Zusätzlich bestimmen wir C-reaktiyes Protein, ThromboplastinzeiL .Partielle Thromboplastinzeit, Leukozyten, Thrombozyten und Gesamteiweiß. Eine PC -gestützte Erfassung von Spender- und Spendedaten gewährleistet eine einfache statistische Auswertung der Entnahme Vorgänge. Die ebenfalls EDV-unterstützte Vergabe der Konservennummern und .BarcodeEtikettierung erleichtem es, die Eigenblutkonserven in der allgemeinen Blutbank-EDV zu verwalten. Durch eine fachübergreifende Zusammenarbeit, z.B. im Rahmen einer Transfusionskommission, müssen die Ablaufe aller fremdblutsparenden Maßnahmen vorgestellt und fortwährend optimiert werden, um Qualität, Akzeptanz und Wirtschaftlichkeit der autologen Blutentnahme zu erhalten.
Die Rate von positiven Blutkulturen wird in der Literatur mit 6,4% bis 18% angegeben. Hierbei wird nicht zwischen Einsendungen zur Bestätigung des Verdachts auf eine Sepsis bzw. zum Ausschluß einer Sepsis unterschieden. In einer prospektiven Untersuchung bei 315 Patienten mit Verdacht auf Sepsis, bei denen Blutkulturen beimpft wurden, konnte bei 199 (63%) ein ätiologischer Nachweis erbracht werden.
Ein Krankenhauslabor und ein Einsendelabor, das mehrere Krankenhäuser versorgt, haben prospektiv 3.907 Blutkulturflaschen für das BACTEC™ 9000–System (BDDiagnostics, Heidelberg, Germany) untersucht. Dabei wurden 1.888 aerobe Flaschen, 1.880 anaerobe Flaschen und 139 pädiatrische Blutkulturflaschen verarbeitet. Es wurden der Zeitpunkt der Beimpfung und der Zeitpunkt des Einlesens der Kulturen in das Gera ̈t dokumentiert. Neben den Medientypen und dem Blutvolumen wurden folgende Daten erhoben: Die Zeit vom Einlesen in das Gerät bis zum positiven Signal (Detektionszeit), die Identifizierung des Erregers bis zur Species, die Antibiotikatherapie und die Wiederfindungsrate verglichen mit der terminalen Subkultur. Die mittlere Transportdauer betrug 21,4 h, die mittlere Detektionszeit 21,5 h. 27 Flaschen waren falsch negativ und sechs Flaschen falsch positiv. Bei sieben der falschnegativen Flaschen hatte die Partnerflasche ein positives Signal gegeben (Staphylococcus aureus, Enterobactercloacae, Enterococcus faecalis, Candida albicans, Burkholderia cepacia, zwei Pseudomonas aeruginosa-Stämme). Davon waren vier Isolate strikte Aerobier, die nichtin der anaeroben Flasche wuchsen, fünf Patienten standen unter Antibiotikatherapie und eine Flasche hatte eine Transportzeit)48 h und ist in dieser Gruppe ebenfalls aufgeführt. 15/27 falsch negative Flaschen hatten eine Transportzeit)48 h, 11 Patienten bekamen in dieser Gruppe eine Antibiotikatherapie. 6/27 falsch negative Flaschen hatten eine Transportzeit-48 h, davon wurden zwei Patienten antibiotisch behandelt. Einmal handelte es sich um C. glabrata, die nicht in der anaeroben Flaschewuchs. Der klinisch relevante Anteil der falsch negativen Blutkulturen (Isolat nicht in der Begleitflasche nachgewiesen), der innerhalb von 48 h in das BACTEC™ 9000-Gerät eingelesen wurde, betrug 0,15%.
Chromaktiviert die Wirkung von Insulin. Bei Typ-1- undTyp-2-Diabetikern reflektierten verminderte Chromgehalte in Leukozyten eine verminderte Chromversorgung. Je schlechter die Diabeteseinstellung, umso niedriger ward er Chromstatus bei Typ-2-Diabetikern. Daher sollte bei diesen Patienten – besonders bei Typ-2-Diabetikern mit schlechter Einstellbarkeit – eine Chromsupplementation erwogen werden, wenn eine sichere Bestimmung der Chromversorgung nicht gewährleistet ist. Kupferionenbesitzen anti- und auch prooxidative Eigenschaften. Hohe Kupferplasmawerte korrelieren mit der Entstehung einer Arteriosklerose. Die Kupferkonzentrationen im Plasma waren bei beiden Diabetikergruppen erhöht, weitererhöhte Werte zeigten Typ-2-Diabetiker mit Hyperlipidämie oder diabetischen Folgeerkrankungen. Um das Risiko für Mikro- und Makroangiopathie oder Nephropathie zu vermindern, sollten Diabetiker eine hohe Kupferzufuhr vermeiden. Selen wirkt antioxidativ, immunstimulierend und antiatherogen. Der Selengehalt im Plasma reflektiert die Selenzufuhr. Die Selenplasmawerte waren bei beiden Diabetesgruppen geringfügig vermindert und auffällig vermindert bei Patienten mit Folgeerkrankungen. Eine selenreiche Ernährung oder Selengaben zur Prävention von Spätfolgen könnten bei Diabetikern daher sinnvoll sein. Patienten mit Nephropathie und eingeschränkter Zufuhr an tierischem, selen- und zinkreichem Protein profitieren möglicherweise von einer Selensupplementation. Zink ist an der Wundheilung, der Immunfunktion und der Aktivierung und Speicherung von Insulin beteiligt. Der Elementgehalt war beiTyp-1-Diabetikern in Leukozyten, dem bestem Indikator der Zinkversorgung, vermindert. Bei Patienten mit Nephropathie, Mikroangiopathie oder Neuropathie war das Zinkdefizit noch deutlicher ausgeprägt. Eine hochwertige, proteinreiche Ernährung könnte die Versorgungslage ver-bessern, auch eine Zinksupplementation wäre möglicherweise von Nutzen.
A comparison of different APTT-reagents, heparin-sensitivity and detection of mild coagulopathies
(1992)
The activated partial thromboplastin time (aPTT) is widely used to detect coagulation abnormalities or to monitor heparin treatment.
Many commercial aPTT-reagents are available which contain different phospholipid reagents and activators. In the present study 3 aPTT-reagents (aPTT-D, Instrumentation Laboratory, Neothromtin, Behring, PTTa, Boehringer) were compared using a computerized centrifugal analyzer. One aPTT-reagent (Pathromtin, Behring) was tested on a semiautomated coagulometer. Instrument precision was evaluated using aPTT-D as reagent.
Comparative tests were performed on plasma samples of 40 healthy donors, 3 patients with mild von Willebrand's disease (vWd), W patients with heaemophilia or subhaemophilia A, 1 patient with subhaemophilia A and vWd, 8 patients treated with subcutaneous injection of unfractionated heparin (UFH) and 14 patients treated with subcutaneous injection of a low molecular weight heparin (LMWH).
aPTT-D was the most sensitive reagent to detect mild vWd while Pathromtin detected none of these defects. In patients with heamophilia A and subhaemophilia A aPTT-D, Neothromtin and PTTa detected the abnormality in nearly all tested samples while Pathromtin was less sensitive.
Patients treated with subcutaneously applied UFH or LMWH often had a prolonged aPTTt especially when aPTT-D and Neothromtin were used as reagents.
Die Zytomegafie ist eine meist lebenslänglich latent bleibende vertikale und horizontale Herpesvirusinfektion mit gelegentlich schweren Krankheitsbildern, auch als Ursache oder Folge von Immunstörungen. Dem Virus wird ein onkogenes Potential zugeschrieben, zuletzt diskutiert bei AIDS und M. Kaposi. Für die Labordiagnose verfügen wir über die Mikroskopie (Zellkerneinschlüsse) und Elektronenmikroskopie, Nachweis der Virusinfektiosität auf Zellkulturen, DNA- und Polypeptidanalyse zur Virusstammidentifikation, direkte DNA- und Antigennachweise aus Patientenmaterial, immunhistologische Methoden (z.B. Immunperoxydase- Technik). Die Untersuchung der Immunzellen erfolgt bei der Zytomegalie quantitativ (T-ZellQuotient) und qualitativ (Lymphozytenstimulierung, neuerdings auch mit Vollblut). Am leichtesten gelingt die Labordiagnose serologisch, d.h. über den Antikörpernachweis. Dafür sind eine Vielzahl „liquid" und „solid phase"-Assays entwickelt worden. Am meisten haben sich heute neben der KB R (und P H A) Immunofluororeszenz und ELISA durchgesetzt, wobei einerseits unterschiedliche Antigene („early", „late antigens") und Antigenpräparationen (z. B. Viruskapsid, -envelope) zum Einsatz kommen, andererseits verschiedene Ig- Klassen und -Subklassen getestet werden, um die primäre und sekundäre Zytomegalie zu diagnostizieren und zu differenzieren. Speziell für den Ig M -Nachweis wurden viele Testmodifikationen etabliert; Rheumafaktorinterferenz und IgG-Kompetition lassen sich am besten durch IgG-Präzipitation ausschalten. Die neuen Methoden haben nicht nur die Aufklärung vieler interessanter Krankheitsfälle, sondern auch exakte epidemiologische Studien bei Risikogruppen ermöglicht (Blutspender: 47[0], schwangere Frauen 56[13], Patienten mit Hämophilie: 69[0], nach NTPL: 90[24], nach Herz-OP: 87[1], Prostituierte: 90[1]% CMV-IgG[(IgM)- Antikörperträger].