Motor skills, cognitive impairment, and quality of life in normal pressure hydrocephalus: early effects of shunt placement

Background Traditionally, clinical fndings of normal pressure hydrocephalus are mainly characterized by the Hakim triad. The aim of this study is to evaluate the performance of patients sufering from idiopathic normal pressure hydrocephalus (iNPH) in a more holistic manner regarding motor skills, cognitive impairment, and quality of life. Methods In total, 30 individuals diagnosed with iNPH as well as a reference group with another 30 individuals were included. The iNPH patients and the reference group were age, educational, and morbidity matched. A standardized test battery for psychomotor skills, gait, neuropsychological abilities as well as questionnaires for quality of life was applied. The iNPH group was tested prior to surgery, at 6 weeks, and 3 months postoperatively. The reference group was tested once. Results Patients showed a signifcant improved performance in various items of the test battery during the frst 3 months postoperatively. This included neuropsychological evaluation, motor skills including gait and upper motor function as well as the quality of life of the patients. Compared to reference individuals, neuropsychological aspects and quality of life of iNPH patients improved in some parts nearly to normal values. Conclusion Our fndings underline that shunt surgery does not only improve the symptoms in iNPH patients but also ame liorates the quality of life to a great extent close to those of age and comorbidity matched reference individuals. This data enables an optimized counseling of iNPH patients regarding the expectable outcome after shunt surgery especially regarding cognitive performance, motor skills as well as life quality

Endoscope-assisted resection of brainstem cavernous malformations

Targeted surgical precision and minimally invasive techniques are of utmost importance for resectioning cavernous malformations involving the brainstem region. Minimisation of the surgical corridor is desirable but should not compromise the extent of resection. This study provides detailed information on the role of endoscopy in this challenging surgical task. A retrospective analysis of medical documentation, radiologic studies and detailed intraoperative video documentation was performed for all consecutive patients who underwent surgical resection of brainstem cavernous malformations between 2010 and 2020 at the authors’ institution. A case-based volumetry of the corticotomy was performed and compared to cavernoma dimensions. A total of 20 procedures have been performed in 19 patients. Neuroendoscopy was implemented in all cases. The mean size of the lesion was 5.4 (± 5) mm3. The average size of the brainstem corticotomy was 4.5 × 3.7 (± 1.0 × 1.1) mm, with a median relation to the cavernoma’s dimension of 9.99% (1.2–31.39%). Endoscopic 360° inspection of the resection cavity was feasible in all cases. There were no endoscopy-related complications. Mean follow-up was 27.8 (12–89) months. Gross-total resection was achieved in all but one case (95%). Sixteen procedures (80%) resulted in an improved or stable medical condition. Eleven patients (61.1%) showed further improvement 12 months after the initial surgery. With the experience provided, endoscopic techniques can be safely implemented in surgery for BSCM. A combination of neuroendoscopic visualisation and neuronavigation might enable a targeted size of brainstem corticotomy. Endoscopy can currently be considered a valuable additive tool to facilitate the preparation and resection of BSCM

From Simulation Data to Test Cases for Fully Automated Driving and ADAS

Part 3: Practical Applications International audience Within this paper we present a new concept on deriving test cases from simulation data and outline challenging tasks when testing and validating fully automated driving functions and Advanced Driver Assistance Systems (ADAS). Open questions on topics like virtual simulation and identification of relevant situations for consistent testing of fully automated vehicles are given. Well known criticality metrics are assessed and discussed with regard to their potential to test fully automated vehicles and ADAS. Upon our knowledge most of them are not applicable to identify relevant traffic situations which are of importance for fully automated driving and ADAS. To overcome this limitation, we present a concept including filtering and rating of potentially relevant situations. Identified situations are described in a formal, abstract and human readable way. Finally, a situation catalogue is built up and linked to system requirements to derive test cases using a Domain Specific Language (DSL). Document type: Part of book or chapter of boo

Impact of MiRNA-181a2 on the Clinical Course of IDH1 Wild Type Glioblastoma

Background: Recently, miRNA-181a2 could be identified as a major regulator of IDH1 expression in fat tissue. The IDH1 gene, its mutation and expression have a major impact on overall survival in patients with glioblastoma. The presented study aimed to investigate the effect of miRNA181a2 on IDH1 expression in glioblastoma and on the prognosis of patients suffering from, for example, a tumor. Methods: A total of 74 glioblastoma specimens were analyzed for the expression of miRNA-181a2, acquired as fold change, using qRT-PCR. IDH1 protein expression was estimated via mRNA quantification. Eight post mortal, non-glioma related brain tissue specimens served as the control group. The results were correlated with relevant demographic and clinical aspects of the cohort. A TCGA dataset was used as an independent reference. Results: MiRNA-181a2 was significantly downregulated in tumor samples compared to the control group (p < 0.001). In the glioblastoma cohort, 63/74 (85.1%) showed an IDH1 wild type, while 11/74 (14.9%) patients harbored an IDH 1 mutation. In patients with IDH1 wild type glioblastoma, low miRNA-181a2 expression correlated with a prolonged overall survival (p = 0.019), also verifiable in an independent TCGA dataset. This correlation could not be identified for patients with an IDH1 mutation. MiRNA-181a2 expression tended to correlate inversely with IDH1 protein expression (p = 0.06). Gross total resection of the tumor was an independent marker for a prolonged survival (p = 0.03). Conclusion: MiRNA181a2 seems to be a promising prognostic marker of selective glioblastoma patients with IDH1 wild type characteristics. This effect may be mediated via direct regulation of IDH1 expression

Elastin is heterogeneously cross-linked

Elastin is an essential vertebrate protein responsible for the elasticity of force-bearing tissues such as those of the lungs, blood vessels, and skin. One of the key features required for the exceptional properties of this durable biopolymer is the extensive covalent cross-linking between domains of its monomer molecule tropoelastin. To date, elastin's exact molecular assembly and mechanical properties are poorly understood. Here, using bovine elastin, we investigated the different types of cross-links in mature elastin to gain insight into its structure. We purified and proteolytically cleaved elastin from a single tissue sample into soluble cross-linked and noncross-linked peptides that we studied by high-resolution MS. This analysis enabled the elucidation of cross-links and other elastin modifications. We found that the lysine residues within the tropoelastin sequence were simultaneously unmodified and involved in various types of cross-links with different other domains. The Lys-Pro domains were almost exclusively linked via lysinonorleucine, whereas Lys-Ala domains were found to be cross-linked via lysinonorleucine, allysine aldol, and desmosine. Unexpectedly, we identified a high number of intramolecular cross-links between lysine residues in close proximity. In summary, we show on the molecular level that elastin formation involves random cross-linking of tropoelastin monomers resulting in an unordered network, an unexpected finding compared with previous assumptions of an overall beaded structure

Bisulfite profiling of the MGMT promoter and comparison with routine testing in glioblastoma diagnostics

Background: Promoter methylation of the DNA repair gene O6 -methylguanine-DNA methyltransferase (MGMT) is an acknowledged predictive epigenetic marker in glioblastoma multiforme and anaplastic astrocytoma. Patients with methylated CpGs in the MGMT promoter beneft from treatment with alkylating agents, such as temozolomide, and show an improved overall survival and progression-free interval. A precise determination of MGMT promoter methyla‑ tion is of importance for diagnostic decisions. We experienced that diferent methods show partially divergent results in a daily routine. For an integrated neuropathological diagnosis of malignant gliomas, we therefore currently apply a combination of methylation-specifc PCR assays and pyrosequencing. Results: To better rationalize the variation across assays, we compared these standard techniques and assays to deep bisulfte sequencing results in a cohort of 80 malignant astrocytomas. Our deep analysis covers 49 CpG sites of the expanded MGMT promoter, including exon 1, parts of intron 1 and a region upstream of the transcription start site (TSS). We observed that deep sequencing data are in general in agreement with CpG-specifc pyrosequencing, while the most widely used MSP assays published by Esteller et al. (N Engl J Med 343(19):1350–1354, 2000. https://doi.org/ 10.1056/NEJM200011093431901) and Felsberg et al. (Clin Cancer Res 15(21):6683–6693, 2009. https://doi.org/10.1158/ 1078-0432.CCR-08-2801) resulted in partially discordant results in 22 tumors (27.5%). Local deep bisulfte sequencing (LDBS) revealed that CpGs located in exon 1 are suited best to discriminate methylated from unmethylated samples. Based on LDBS data, we propose an optimized MSP primer pair with 83% and 85% concordance to pyrosequencing and LDBS data. A hitherto neglected region upstream of the TSS, with an overall higher methylation compared to exon 1 and intron 1 of MGMT, is also able to discriminate the methylation status. Conclusion: Our integrated analysis allows to evaluate and redefne co-methylation domains within the MGMT pro‑ moter and to rationalize the practical impact on assays used in daily routine diagnostics

Identification of relevant traffic situations for scenario-based development of automated driving functions

Automatisiertes Fahren wird die zukünftige Mobilität grundlegend verändern. Die fortschreitende Digitalisierung bildet die Grundlage für technische Innovationen und Automatisierung der Fahraufgabe. Zahlreiche medienwirksame Auftritte verschiedener Firmen und Forschungsgruppen zeigen die technische Machbarkeit automatisierter Fahrfunktionen. Vor allem die steigende Komplexität zukünftiger Fahrfunktionen beinhaltet große Herausforderungen für die Entwicklung, Test und Freigabe. Derartige Systeme sollen die Fahraufgabe in definierten Verkehrsdomänen komplett übernehmen. Die Fahrfunktion muss alle auftretenden Situationen sicher beherrschen. Die Identifikation aller dafür relevanten Verkehrssituationen kann mit bekannten Methoden der Situationsanalyse nicht bewerkstelligt werden. Etwaige Methoden fokussieren nicht auf typische, normale und unkritische Verkehrssituationen, wenngleich diese für die Anforderungsanalyse und Spezifikation automatisierter Fahrfunktionen notwendig sind. Um die steigende Komplexität zu bewältigen, werden von der Forschung und Fachliteratur szenarienbasierte Methoden für die Entwicklung automatisierter Fahrfunktionen vorgeschlagen. Die vorliegende Arbeit präsentiert eine Methode zur Identifikation typischer Verkehrssituationen. Die Methodik basiert auf einem menschlichen Entscheidungsfindungsmodell und beinhaltet ein systematisches Vorgehen. Sie berücksichtigt Expertenwissen, sowie funktions- und entwicklungsspezifisch relevante Situationsmerkmale. Das systematische Vorgehen nutzt Simulationsmethoden zur Datenerhebung sowie Constraint-Programmierung. Somit wird das Constraint-Erfüllungs-Problem zur Suche nach relevanten Situationen in einer deklarativen Weise beschrieben. Die Validierung zeigt, dass relevante und typische Situationen identifiziert werden können, an die in einem unstrukturierten Vorgehen während der Anforderungsanalyse und Spezifikation des Zielsystems unter Umständen nicht gedacht wird. Zusammen mit dem durchgängigen szenarienbasierten Entwicklungsansatz SBSE zeigt die Situationsidentifikation großes Potential für die Entwicklung automatisierter Fahrfunktionen. Zudem bildet der vorgestellte Ansatz die Grundlage für weitere Forschung im Bereich der szenarienbasierten Entwicklung.Automated driving will fundamentally change future mobility. The progressive digitalisation forms the basis for technological innovation and automation of the driving task. Numerous media-effective presentations of various companies and research groups prove the technical feasibility of automated driving functions. Especially the growing complexity of future driving functions holds enormous challenges for development, test and release procedure. The aim of such systems is to completely assume the driving task in a defined environment. The driving function must control all upcoming traffic situations in a reliable way. The identification of all relevant traffic situations cannot be achieved with known methods for situation analysis. Those methods do not focus on typical, normal and non-critical traffic situations, although they are relevant for requirement analysis and specification of the target system. To overcome the complexity of developing automated driving functions, research and literature propose scenario-based methods. This contribution presents a method for identifying typical traffic situations. On the basis of a model for human decision making, the method implies a systematic approach for situation identification. Expert knowledge, as well as function- and development-specific relevant situational attributes are taken into account. The systematic approach utilises simulation methods for data collection as well as the usage of constraint programming. Thus, the constraint-satisfaction-problem for searching relevant situations is described in a declarative manner. The validation of the proposed method shows, that relevant situations can be identified, which may not be found in an unstructured procedure for requirement analysis and specification of the target system. Together with the scenario-based development approach SBSE, the method for situation identification shows great potential for developing automated driving functions. Moreover, the presented method constitutes the basis for further research in scenario-based development

A Credibility Assessment Approach for Scenario-Based Virtual Testing of Automated Driving Functions

An immense test space is pushing the development and testing of automated driving functions from real to virtual environments. The virtual world is provided by interconnected simulation models representing sensors, vehicle dynamics, and both static and dynamic environment. For the virtual validation of automated driving, special attention must be paid to the simulation&#x2019;s credibility, which can be impaired by inappropriate or inaccurate simulation models and tools. Therefore, in this work a method is proposed to assess the credibility of simulation-based testing for automated driving. The approach allows a qualitative and relatively quantitative comparisons between scenarios as well as between different simulation setups. Therefore, several uni- and multivariate metrics are applied towards a scoring of similarity of the behavior between simulation and real test drive. This is achieved by using ground truth data in form of simulation scenarios from real world measurement data. In this way, the virtual automated vehicle encounters the same conditions and surroundings than its counterpart in the real world for evaluating their similarity. The practical applicability of the proposed credibility assessment approach is demonstrated in a case study, in which the credibility of an exemplary simulation-based test bench is inferred