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The Tunnel Oberau, with a length of 2.9 km, forms the core of the local bypass of Oberau. Between the two massifs Kirchbichl and Muhlberg, the tunnel is situated in the valley of the Giesenbach in alluvial gravel with only a small overlap underneath settlement-sensitive buildings. In this paper, the measures in the tunnel to minimize the settlements of the buildings during the shotcrete excavations are described. Basis for this planning were extensive 3D-FE-calculations. Furthermore, under two buildings a compensation grouting measure was carried out, in order to compensate the occurring settlements. This paper describes how the required time and the amount of injection material (grout) could be reduced during the compensation grouting in highly permeable gravel.

Head and neck squamous cell carcinomas (HNSCC) are the sixth most common malignancies worldwide. 45% of patients are diagnosed at a late tumor stage associated with poor survival. For metastatic, unresectable or recurrent (m/uR) HNSCC, immune checkpoint inhibition (ICI) was recently approved as a novel therapeutic option showing significant survival benefits compared to standard chemotherapy-based treatment. However, response to ICI is still limited to a small number of patients calling for further improvement of T cell-based immunotherapies. Peptide-based approaches, which rely on the specific immune recognition of tumor-associated human leukocyte antigen (HLA) presented peptides, represent promising and low side effect treatment options. Peptide vaccination has been shown to enhance and induce long-term anti-tumoral immune responses and even clinical responses in HNSCC patients. However, current vaccines are either monovalent, based on patient-individual tumor-specific mutations or restricted to a single HLA allotype and therefore neither widely applicable nor suitable for reliable studies and large-scale production. In this study, using mass spectrometry (MS) -based immunopeptidome analysis of a large cohort of HNSCC patient (n = 30) tumor and adjacent benign samples, we established a tumor-associated off-the-shelf peptide warehouse for broadly applicable personalized therapies. The malignant dataset, comprising 91651 HLA ligands, was compared to adjacent benign and various benign tissues (www.hla-ligand-atlas.org) to identify tumor-exclusive antigens. Further antigen selection was based on allotype-specific high frequent presentation. In total, 23 frequently presented and tumor-exclusive HNSCC-associated peptides were selected for six of the most common HLA class I allotypes (A*01, A*02, A*24, B*15, B*35, B*40) covering >75% of the world population, as well as five HLA class II presented peptides binding various different HLA class II allotypes. Immunogenicity was validated by IFN-γ ELISPOT screening for spontaneous preexisting T cell responses targeting the respective peptides as well as by in vitro priming experiments of naïve T cells in HNSCC patients and healthy volunteers. Furthermore, immunopeptidome analyses identified these antigens in patient plasma samples providing first evidence for “liquid biopsy” immunopeptidome analysis without the need of primary tumor tissue. A phase I study evaluating safety, immunogenicity as well as first efficacy of this warehouse-based vaccine in combination with ICI in HNSCC patients is currently being set up, with personalized peptide selection based on individual HLA-allotype and MS analysis of patient tumor/plasma sample. In conclusion, we here designed a peptide warehouse that enables a polyvalent and widely applicable but still personalized peptide vaccination in HNSCC patients. Citation Format: Sarah Schroeder, Thorben Gross, Annika Nelde, Marcel Wacker, Jens Bauer, Jonas Rieth, Marissa Dubbelaar, Lena Muehlenbruch, Yacine Maringer, Paul-Stefan Mauz, Martin Sailer, Julia Philipp, Sven Becker, Thomas Breuer, Helmut R. Salih, Hans-Georg Rammensee, Hubert Löwenheim, Juliane S. Walz. Immunopeptidomics-guided tumor antigen warehouse design for peptide-based immunotherapy in head and neck squamous cell carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3555.

Background and Purpose: The purpose of this study was to assess nationwide incidence and outcomes of aneurysmal subarachnoid hemorrhage (aSAH). The Swiss SOS (Swiss Study on Subarachnoid Hemorrhage) was established in 2008 and offers the unique opportunity to provide this data from the point of care on a nationwide level. Methods: All patients with confirmed aneurysmal subarachnoid hemorrhage admitted between January 1, 2009 and December 31, 2014, within Switzerland were recorded in a prospective registry. Incidence rates were calculated based on time-matched population data. Admission parameters and outcomes at discharge and at 1 year were recorded. Results: We recorded data of 1787 consecutive patients. The incidence of aneurysmal subarachnoid hemorrhage in Switzerland was 3.7 per 100 000 persons/y. The number of female patients was 1170 (65.5%). With a follow-up rate of 91.3% at 1 year, 1042 patients (58.8%) led an independent life according to the modified Rankin Scale (0–2). About 1 in 10 patients survived in a dependent state (modified Rankin Scale, 3–5; n=185; 10.4%). Case fatality was 20.1% (n=356) at discharge and 22.1% (n=391) after 1 year. Conclusions: The current incidence of aneurysmal subarachnoid hemorrhage in Switzerland is lower than expected and an indication of a global trend toward decreasing admissions for ruptured intracranial aneurysms. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03245866.

Doublecortin (DCX) is a microtubule-associated protein widely used as an indicator of neurogenesis in immunohistochemical analyses of the postmortem adult brain. A recent study reported that DCX can be quantified in the cerebrospinal fluid (CSF) from healthy rats between postnatal day 0 (P0) and P30. However, it is currently unclear whether the concentration of DCX in the CSF (CSF-DCX) may represent a measure of endogenous neurogenesis. To address this question, this study examined the impact of a neonatal hypoxic-ischemic (HI) brain injury, known to induce neurogenesis, on CSF-DCX. HI was elicited at P7 in Sprague-Dawley rat neonates, and CSF was collected serially from the cisterna magna at P5 and P10, or at P10 and P15. A sandwich immunoassay was used to measure CSF-DCX. Brains from P10 neonates were analyzed immunohistochemically for neurogenesis and cell death markers. Mean CSF-DCX was significantly higher in HI- than in sham-exposed animals, at both P10 and P15. In the HI group at P10, CSF-DCX and stroke severity correlated positively. DCX immunoreactivity was increased in the ipsilateral neurogenic niches from the P10 HI brains in comparison with that of shams. The number of proliferative DCX-positive cells was higher in the ipsilateral hippocampal subgranular zone (SGZ) than in the HI contralateral or sham SGZ. Thus, neonatal HI brain injury disrupts the developmental time-course of DCX levels in the CSF. Our data suggest that the increased concentration of DCX in the CSF after neonatal HI is the result of both cellular injury and increased neurogenesis.

BACKGROUND We recently demonstrated that 86% of the patients treated with peripheral nerve stimulation (PNS) for therapy-refractory sacroiliac joint (SIJ) pain were satisfied with the result after 1 year of treatment. OBJECTIVE To investigate the long-term (up to 4 years) response rate of this novel treatment. METHODS Sixteen consecutive patients with therapy-refractory SIJ pain were treated with PNS and followed for 4 years in 3 patients, 3 years in 6 patients, and 2 years in 1 patient. Quality of life, pain, and patient satisfaction were assessed using the Oswestry Disability Index 2.0, Visual Analog Scale (VAS), and International Patient Satisfaction Index. RESULTS Patients reported a pain reduction from 8.8 to 1.6 (VAS) at 1 year ( P < .001), and 13 of 14 patients (92.9%) rated the therapy as effective (International Patient Satisfaction Index score ≤ 2). At 2 years, average pain score was 1.9 ( P < .001), and 9 of 10 patients (90.0%) considered the treatment a success. At 3 years, 8 of 9 patients (88.9%) were satisfied with the treatment results, reporting an average VAS of 2.0 ( P < .005). At 4 years, 2 of 3 patients were satisfied with the treatment results. CONCLUSION We have shown for the first time that PNS is a successful long-term therapy for SIJ pain.

Die 2. S-Bahn-Stammstrecke München ist ein Projekt mit besonderen geotechnischen Herausforderungen. Die Grenzen bisheriger Erfahrungen in München werden mit den geplanten Baumaßnahmen – insbesondere den über 40 m tiefen Baugruben oder den circa 340 m² großen Spritzbetonvortrieben an den Haltepunkten Hauptbahnhof und Marienhof – überschritten. Derartige Baumaßnahmen führen zu außergewöhnlichen Fragestellungen, zu deren Klärung für die 2. S-Bahn-Stammstrecke München verschiedene geotechnische Sonderuntersuchungen ausgeführt wurden. Im Rahmen der Veröffentlichung werden zum einen Sonderuntersuchungen zum geplanten Hydroschildvortrieb vorgestellt. Es wird auf den Zerfall feinkörniger Böden und den damit verbunden Aufwand bei der Separierung sowie auf die Beurteilung der Abrasivität im Lockergestein eingegangen. Zum anderen wird die Vorgehensweise zur Ermittlung tunnelbauinduzierter Setzungen sowie die Ausführung von Hebungsinjektionen zur Anhebung einer bestehenden U-Bahntunnelröhre erläutert.

Spinal epidural abscess (SEA) is a rare, but serious, condition with multiple causes. We prospectively studied the aetiology, predisposing factors, and clinical outcomes of SEA in all patients with SEA treated in our hospital’s neurosurgical service from 2004 to 2008. For each patient, we recorded the medical history, comorbidities, focus of infection, pathogen(s), and outcome. The 36 patients (19 women and 17 men) ranged in age from 34 to 80 years old (mean 57; median 56). The SEA was primary (i.e., due to haematogenous spread) in 16 patients (44%); it was secondary to elective spinal procedures, either injections or surgery, in 20 patients (56%). The duration of follow-up was 12–60 months (mean 36; median 37.5). The most common pathogen, Staphylococcus aureus, was found in 18 patients (50%). Patients with primary SEA had different underlying diseases and a wider range of pathogens than those with secondary SEA. Only five patients (14%) had no major comorbidity; 16 of the 20 patients with secondary SEA (44% of the overall group) had undergone spinal surgery before developing the SEA; the treatment of the SEA involved multiple surgical operations in all 16 of these patients, and spinal instrumentation in 5 (14%); 22 patients (61% of the overall group) recovered fully.

Complete surgical resection beyond tumor margins cannot be achieved in glioblastoma multiforme (GBM) because of infiltrative nature. In several cancers, neoadjuvant treatment has been implemented to reduce the risk of tumor cell spreading during resection. In GBM, the objective of a neoadjuvant approach is reduction of tumor cells within the main tumor mass and beyond in the infiltration zone. Such an approach can only be performed if elevated intracranial pressure can be medically controlled. In a previous study with recurrent gliomas, we showed that local intratumoral injection of radiolabeled DOTAGA-substance P substantially inhibited further growth and led to radionecrotic transformation of the tumor (CCR 2006). We have now examined this modality as neoadjuvant treatment for GBM, primarily assessing feasibility, toxicity, the extent of resection, and functional outcome. After diagnosis of GBM, 17 patients were included in a prospective phase I study. Repetitive intratumoral injections of radiolabeled DOTAGA-substance P were performed, followed by surgical resection. Chemical synthesis, radiolabeling, and local injection of the peptidic vector [90Yttrium]-DOTAGA-substance P were described previously. Neoadjuvant injection of [90Y]-DOTAGA-substance P was feasible without decompensation of intracranial pressure. Prolonged application of corticosteroids was identified as the main risk factor for side effects. Fifteen patients stabilized or improved their functional status. The mean extent of resection in subsequent surgery was 96%. Neoadjuvant therapy of GBM using locally injected radiolabeled DOTAGA-substance P was feasible and of low toxicity. The high extent of resection and concomitant irradiation of tumor cells in the infiltration zone may be prognostically relevant.

There are numerous disease conditions emerging from mutations in genes or alterations in gene expression for which gene-based therapies provide the most promising treatment modality. However, expression of therapeutic genes and proper localization of the expressed proteins require a complex interactive environment within the target cells or tissues for ultimately being clinically applicable. Our knowledge of molecular pathways, cell biology, and the immune system has helped in the development of a variety of drugs that can modulate these processes. Historically, gene therapies and pharmacologic therapies have remained mutually exclusive methods of tackling a disease. In this chapter, we will provide an alternate perspective that will bring together both schools of thought. In specific cases, if conducive to the disease mechanism and the underlying pathology, a pharmacologic drug can help enhance and regulate a gene therapy or vice versa. Such combined approaches can hence increase the specificity and efficiency of the final therapy which may be much better than the individual ones. There are many hurdles to such dual-modality processes and hence must be employed after careful evaluation of the proposed positive and negative outcomes at a molecular level. We will provide specific examples of such collaborative pharmacologic and gene-based therapeutic strategies and discuss how similar strategies may be beneficial in different diseases.

Dynamic stabilization devices were developed to reduce spinal hypermobility while preserving a certain degree of physiological motion. Our goal was to assess radiographic and clinical outcomes of patients treated with surgical decompression and stabilization with the LimiflexTM implant. We investigated the effect of LimiFlex implantation on post-operative translation and angulation in 36 patients with spinal stenosis and degenerative spondylolisthesis Meyerding Grade I treated with decompression and dynamic stabilization. Significant improvements following lumbar decompression were observed. The average Oswestry Disability Index (ODI) score fell from 45.9 Pre-operatively to 29.6 at dismissal and 26.5 at first follow up. The average visual analog scale (VAS) score fell from 7 Pre-operatively to 3 at dismissal and 3 at follow up. Pre-operatively the median translation within the operated segment was 2.0 mm. Post-operatively the translation was reduced to 0.7 mm (p=0.006, Student’s t-test). Pre-operatively the median rotation within the operated segment was 4.6°. Post-operatively the rotation was reduced to 3.5° (p=0.08, Student’s t-test). The re-operation rate was 6 out of 36 (16.7%). Here we provide evidence suggesting that the dynamic paraspinous stabilization implant LimiflexTM is well tolerated in patients with degenerative spondylolisthesis and lumbar spinal canal stenosis. Our data show that within 3 months after the operation it limits hypermobility in the operated segment. This might be well suited in cases such as spinal stenosis with Grade I degenerative spondylolisthesis, where instability at the operated segment is likely to happen, but a patient is not indicated for a spinal fusion.

Epithelial to mesenchymal transition (EMT) describes the process of epithelium transdifferentiating into mesenchyme. EMT is a fundamental process during embryonic development that also commonly occurs in glioblastoma, the most frequent malignant brain tumor. EMT has also been observed in multiple carcinomas outside the brain including breast cancer, lung cancer, colon cancer, gastric cancer. EMT is centrally linked to malignancy by promoting migration, invasion and metastasis formation. The mechanisms of EMT induction are not fully understood. Here we describe an in vitro system for standardized isolation of cortical neural stem cells (NSCs) and subsequent EMT-induction. This system provides the flexibility to use either single cells or explant culture. In this system, rat or mouse embryonic forebrain NSCs are cultured in a defined medium, devoid of serum and enzymes. The NSCs expressed Olig2 and Sox10, two transcription factors observed in oligodendrocyte precursor cells (OPCs). Using this system, interactions between FGF-, BMP- and TGFβ-signaling involving Zeb1, Zeb2, and Twist2 were observed where TGFβ-activation significantly enhanced cell migration, suggesting a synergistic BMP-/TGFβ-interaction. The results point to a network of FGF-, BMP- and TGFβ-signaling to be involved in EMT induction and maintenance. This model system is relevant to investigate EMT in vitro. It is cost-efficient and shows high reproducibility. It also allows for the comparison of different compounds with respect to their migration responses (quantitative distance measurement), and high-throughput screening of compounds to inhibit or enhance EMT (qualitative measurement). The model is therefore well suited to test drug libraries for substances affecting EMT.

In the present study we investigated the phosphorylation status of the 12 most important signaling cascades in glioblastomas. More than 60 tumor and control biopsies from tumor center and periphery (based on neuronavigation) were subjected to selective protein expression analysis using reverse-phase protein arrays (RPPA) incubated with antibodies against posttranslationally modified cancer pathway proteins. The ratio between phosphorylated (or modified) and non-phosphorylated protein was assessed. All samples were histopathologically validated and proteomic profiles correlated with clinical and survival data. By RPPA, we identified three distinct activation patterns within glioblastoma defined by the ratios of pCREB1/CREB1, NOTCH-ICD/NOTCH1, and pGSK3β/GSK3β, respectively. These subclasses demonstrated distinct overall survival patterns in a cohort of patients from a single-institution and in an analysis of publicly available data. In particular, a high pGSK3β/GSK3β-ratio was associated with a poor survival. Wnt-activation/GSK3β-inhibition in U373 and U251 cell lines halted glioma cell proliferation and migration. Gene expression analysis was used as an internal quality control of baseline proteomic data. The protein expression and phosphorylation had a higher resolution, resulting in a better class-subdivision than mRNA based stratification data. Patients with different proteomic profiles from multiple biopsies showed a worse overall survival. The CREB1-, NOTCH1-, GSK3β-phosphorylation status correlated with glioma grades. RPPA represent a fast and reliable tool to supplement morphological diagnosis with pathway-specific information in individual tumors. These data can be exploited for molecular stratification and possible combinatorial treatment planning. Further, our results may optimize current glioma grading algorithms.

We report two cases of unclear granulomatous encephalitis where pathogenic algae, genus Prototheca, were identified as causative agent. Granulomatous encephalitis is - after exclusion of cause - per definition diagnosed and managed as neurosarcoidosis. However, protothecal infections go undetected by standard bacterial and fungal rDNA screening. As cerebral protothecosis is potentially treatable, raising awareness for this condition is relevant, because therapeutic immunosuppression is to be avoided. This article is protected by copyright. All rights reserved.

Object Cerebrospinal fluid leakage is an immanent risk of cranial surgery with dural opening. Recognizing the risk factors for this complication and improving the technique of dural closure may reduce the associated morbidity and its surgical burden. The aim of this paper was to investigate whether the addition of TachoSil on top of the dural suture reduces postoperative CSF leakage compared with dural suturing alone and to assess the frequency and risk factors for dural leakage and potentially related complications after elective craniotomy. Methods The authors conducted a prospective, randomized, double-blinded single-center trial in patients undergoing elective craniotomy with dural opening. They compared their standard dural closure by running suture alone (with the use of a dural patch if needed) to the same closure with the addition of TachoSil on top of the suture. The primary end point was the incidence of CSF leakage, defined as CSF collection or any open CSF fistula within 30 days. Secondary end points were the incidence of infection, surgical revision, and length of stay in the intensive care unit (ICU) or intermediate care (IMC) unit. The site of craniotomy, a history of diabetes mellitus, a diagnosis of meningioma, the intraoperative need of a suturable dural substitute, and blood parameters were assessed as potential risk factors for CSF leakage. Results The authors enrolled 241 patients, of whom 229 were included in the analysis. Cerebrospinal fluid leakage, mostly self-limiting subgaleal collections, occurred in 13.5% of patients. Invasive treatment was performed in 8 patients (3.5%) (subgaleal puncture in 6, lumbar drainage in 1, and surgical revision in 1 patient). Diabetes mellitus, a higher preoperative level of C-reactive protein (CRP), and the intraoperative need for a dural patch were positively associated with the occurrence of the primary end point (p = 0.014, 0.01, and 0.049, respectively). Cerebrospinal fluid leakage (9.7% vs 17.2%, OR 0.53 [95% CI 0.23–1.15], p = 0.108) and infection (OR 0.18 [95% CI 0.01–1.18], p = 0.077) occurred less frequently in the study group than in the control group. TachoSil significantly reduced the probability of staying in the IMC unit for 1 day or longer (OR 0.53 [95% CI 0.27–0.99], p = 0.048). Postoperative epidural hematoma and empyema occurred in the control group but not in the study group. Conclusions Dural leakage after elective craniotomy/durotomy occurs more frequently in association with diabetes mellitus, elevated preoperative CRP levels, and the intraoperative need of a dural patch. This randomized controlled trial showed no statistically significant reduction of postoperative CSF leakage and surgical site infections upon addition of TachoSil on the dural suture, but there was a significant reduction in the length of stay in the IMC unit. Dural augmentation with TachoSil was safe and not related to adverse events. Clinical trial registration no. NCT00999999 (http://www.ClinicalTrials.gov).

In a previous immunohistochemical study we observed muscarinic acetylcholine receptors in primary and metastatic human melanomas, which were not present in normal skin melanocytes. In the present study we demonstrated the endogenous expression of muscarinic receptors, of choline acetyltransferase and of cholinesterase activity in the human melanoma cell line SK-mel 28. We tested the effect of muscarinic agonists on cellular movements of the melanoma cells in a perfusion chamber by digital video time-lapse microscopy. Within 3 to 10 min after onset of muscarinic perfusion cell body contractions and retraction of cell processes of more than 5 micrometer occurred in about 30% of the melanoma cells. The effect disappeared after addition of atropine. The proportion of reacting cells corresponded to the endogenous expression of muscarinic receptors revealed by immunocytochemistry with the monoclonal antibody M35. The experiments indicate the presence of an autocrine muscarinic cholinergic system in the melanoma cells and demonstrate a direct link between muscarinic receptors and the contractile apparatus. Melanocytes are derived from neural crest cells that express cholinesterase activity and muscarinic receptors during their migratory phase in the embryo. Therefore, re-expression of the muscarinic cholinergic system in tumour cells may be involved in invasive growth.

BACKGROUND Neuropsychological deficits (NPD) are common in patients with aneurysmal subarachnoid haemorrhage (aSAH). NPD are one of the major limiting factors for patients with an otherwise acceptable prognosis for sustained quality of life. There are only a few studies reporting outcome after aSAH, which used a standardized neuropsychological test battery as a primary or secondary outcome measure. Aim of this study was to determine the current practice of reporting NPD following aSAH in clinical studies. METHODS A MEDLINE analysis was performed using the search term "subarachnoid haemorrhage outcome". The latest 1,000 articles were screened. We recorded study design, number of patients, and the presence of neuropsychological outcome report. Additionally, the time of testing after aSAH, the neuropsychological tests administered, as well as the percentage of patients with NPD were analyzed. RESULTS A total of 324 publications between 2009 and 2012 were selected for further review. Of those, 21 studies (6.5%) reported neuropsychological outcome, in 2,001 of 346,666 patients (0.6%). The assessment of NPD differed broadly using both subjective and objective cognitive evaluation, and a large variety of tests were used. CONCLUSION Neuropsychological outcome is underreported, and there is great variety in assessment in currently published clinical articles on aSAH. Prospective randomized trials treating aSAH may benefit from implementing more comprehensive and standardized neuropsychological outcome measures. This approach might identify otherwise unnoticed treatment effects in future interventional studies of aSAH patients.

Neural stem cells (NSCs) typically show efficient self-renewal and selective differentiation. Their invasion potential, however, is not well studied. In this study, Sox2-positive NSCs from the E14.5 rat cortex were found to be non-invasive and showed only limited migration in vitro. By contrast, FGF2-expanded NSCs showed a strong migratory and invasive phenotype in response to the combination of FGF2 and BMP4. Invasive NSCs expressed Podoplanin (PDPN) and p75NGFR (Ngfr) at the plasma membrane after exposure to FGF2 and BMP4. FGF2 and BMP4 together upregulated the expression of Msx1, Snail1, Snail2, Ngfr, which are all found in neural crest (NC) cells during or after epithelial-mesenchymal transition (EMT), but not in forebrain stem cells. Invasive cells downregulated the expression of Olig2, Sox10, Egfr, Pdgfra, Gsh1/Gsx1 and Gsh2/Gsx2. Migrating and invasive NSCs had elevated expression of mRNA encoding Pax6, Tenascin C (TNC), PDPN, Hey1, SPARC, p75NGFR and Gli3. On the basis of the strongest upregulation in invasion-induced NSCs, we defined a group of five key invasion-related genes: Ngfr, Sparc, Snail1, Pdpn and Tnc. These genes were co-expressed and upregulated in seven samples of glioblastoma multiforme (GBM) compared with normal human brain controls. Induction of invasion and migration led to low expression of differentiation markers and repressed proliferation in NSCs. Our results indicate that normal forebrain stem cells have the inherent ability to adopt a glioma-like invasiveness. The results provide a novel in vitro system to study stem cell invasion and a novel glioma invasion model: tumoral abuse of the developmental dorsoventral identity regulation.

Auricular cartilage is an important source of grafts for various reconstructive procedures such as aesthetic rhinoplasty. The purpose of this investigation was to compare tragal cartilage with auricular cartilage harvested from the concha and scapha, and describe its clinical viability, indications, and morbidity in rhinoplasty. A total of 150 augmentation rhinoplasties with a total of 170 grafts were included. The donor sites were tragus (n=136), concha (n=26), and scapha (n=8). The time needed to harvest the grafts, the donor site morbidity, and the indications for operation were recorded. The anthropometric changes to 4 auricular variables after the cartilage had been harvested were analysed and compared with those on the opposite side in 48 patients using Student's paired t-test. Intraobserver reliability was assessed using Pearson's intraclass correlation. The mean (SD) harvesting time was 27 (8) min for the concha, 4.5 (1.4) min for the tragus, and 5.7 (1.6) min for the scapha. The largest graft was taken from the concha (28×19 mm), followed by the tragus (20×12 mm), and the scapha (18×6 mm). The grafts were placed at the following sites: tip grafts (n=123), columella struts (n=80), shield (n=20), rim (n=17), and dorsal onlay (n=15). Harvesting tragal cartilage is safe, simple, fast, and has a low morbidity, but it can affect the patient's ability to wear earphones. Tragal cartilage is a good alternative for nasal reconstruction if a graft of no longer than 20 mm is required.

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is a haemorrhagic form of stroke and occurs in a younger population compared with ischaemic stroke or intracerebral haemorrhage. It accounts for a large proportion of productive life-years lost to stroke. Its surgical and medical treatment represents a multidisciplinary effort. Due to the complexity of the disease, the management remains difficult to standardise and quality of care is accordingly difficult to assess. Objective: To create a registry to assess management parameters of patients treated for aSAH in Switzerland. Methods: A cohort study was initiated with the aim to record characteristics of patients admitted with aSAH, starting January 1st 2009. Ethical committee approval was obtained or is pending from the institutional review boards of all centres. In the study period, seven Swiss hospitals (five university [U], two non-university medical centres) harbouring a neurosurgery department, an intensive care unit and an interventional neuroradiology team so far agreed to participate in the registry (Aarau, Basel [U], Bern [U], Geneva [U], Lausanne [U], St. Gallen, Zürich [U]). Demographic and clinical parameters are entered into a common database. Discussion: This database will soon provide (1) a nationwide assessment of the current standard of care and (2) the outcomes for patients suffering from aSAH in Switzerland. Based on data from this registry, we can conduct cohort comparisons or design diagnostic or therapeutic studies on a national level. Moreover, a standardised registration system will allow healthcare providers to assess the quality of care

Several types of cysts in the mediastinum have been described, such as bronchogenic or thymic cysts and esophageal duplications, most of which arise in the middle or posterior mediastinum close to the tracheobronchial system or the esophagus. We present herein the rare case of a ciliated cyst anatomically distant to the genitourinary organs. An abnormal formation in the posterior mediastinum was incidentally detected on chest X-ray during the preoperative evaluation for a herniorrhaphy in a 54-year-old woman who had a negative medical history. The patient exhibited no clinical signs or symptoms associated with the mass. MRI revealed hypointense signals in T1-weighted scans and homogeneous hyperintense signals in T2-weighted scans. The lesion was resected thoracoscopically and histologic and immunohistochemical stainings showed a ciliated cyst of probable Mullerian origin. Because of their uncertain biological behavior, cystic lesions in the posterior mediastinum should be removed surgically to allow definitive histologic diagnosis.

CNS stem cells are best characterized by their ability to self-renew and to generate multiple differentiated derivatives, but the effect of mitogenic signals, such as fibroblast growth factor 2 (FGF2), on the positional identity of these cells is not well understood. Here, we report that bone morphogenetic protein 2 (BMP2) induces telencephalic CNS stem cells to fates characteristic of neural crest and choroid plexus mesenchyme, a cell type of undetermined lineage in rodents. This induction occurs both in dissociated cell culture and cortical explants of embryonic day 14.5 (E14.5) embryos, but only when cells have been exposed to FGF2. Neither EGF nor IGF1 can substitute for FGF2. An early step in this response is activation of β-catenin, a mediator of Wnt activity. The CNS stem cells first undergo an epithelial-to-mesenchymal transition and subsequently differentiate to smooth-muscle and non-CNS glia cells. Similar responses are seen with stem cells from E14.5 cortex, E18.5 cortex and adult subventricular zone, but with a progressive shift toward gliogenesis that is characteristic of normal development. These data indicate that FGF2 confers competence for dorsalization independently of its mitogenic action. This rapid and efficient induction of dorsal fates may allow identification of positional identity effectors that are co-regulated by FGF2 and BMP2.

The paradigm shift from device-oriented to service-oriented management has also implications to the area of event correlation. Today's event correlation mainly addresses the correlation of events as reported from management tools. However, a correlation of user trouble reports concerning services should also be performed. This is necessary to improve the resolution time and to reduce the effort for keeping the service agreements. We refer to such a type of correlation as service-oriented event correlation. The necessity to use this kind of event correlation is motivated in the paper.To introduce service-oriented event correlation for an IT service provider, an appropriate modeling of the correlation workflow and of the information is necessary. Therefore, we examine the process management frameworks IT Infrastructure Library (ITIL) and enhanced Telecom Operations Map (eTOM) for their contribution to the workflow modeling in this area. The different kinds of dependencies that we find in our general scenario are then used to develop a workflow for the service-oriented event correlation. The MNM Service Model, which is a generic model for IT service management proposed by the Munich Network Management (MNM) Team, is used to derive an appropriate information modeling. An example scenario, the Web Hosting Service of the Leibniz Supercomputing Center (LRZ), is used to demonstrate the application of service-oriented event correlation.