The transnasal approach to the skull base. From sinus surgery to skull base surgery

The indications for endonasal endoscopic approaches to diseases of the skull base and its adjacent structures have expanded considerably during the last decades. This is not only due to improved technical possibilities such as intraoperative navigation, the development of specialized instruments, and the compilation of anatomical studies from the endoscopic perspective but also related to the accumulating experience with endoscopic procedures of the skull base by multidisciplinary centers. Endoscopic endonasal operations permit new approaches to deeply seated lesions and are characterized by a reduced manipulation of neurovascular structures and brain parenchyma while at the same time providing improved visualization. They reduce the trauma caused by the approach, avoid skin incisions and minimize the surgical morbidity. Transnasal endoscopic procedures for the closure of small and large skull base defects have proven to be reliable and more successful than operations with craniotomies. The development of new local and regional vascularized flaps like the Hadad-flap have contributed to this. These reconstructive techniques are furthermore effectively utilized in tumor surgery in this region. This review delineates the classification of expanded endonasal approaches in detail. They provide access to lesions of the anterior, middle and partly also to the posterior cranial fossa. Successful management of these complex procedures requires a close interdisciplinary collaboration as well as continuous education and training of all team members

Enhancement of an MBSE-supported methodology for managing engineering changes using the example of a machine tool

Engineering changes are often classified as critical and lead to high costs. The reason for this is the high system complexity. To deal with high complexity, MBSE can be used as an approach. However, in order to be able to operate model-based engineering change management, suitable approaches are required. The Advanced Engineering Change Impact Approach - AECIA presents a holistic methodology for model-based change management by supporting change request validity checking, change propagation and change impact analysis, and change information communication in an agile development environment. In this publication, the methodology is extended to include a procedure for checking the validity of change requests, applied to a real change case using a machine tool as an example, and initially evaluated

DESCRIPTIVE ATTRIBUTES OF ANALYSIS USE CASES IN THE DATA-DRIVEN VALIDATION OF ELEMENTS IN THE SYSTEM OF OBJECTIVES

Usage data of reference systems can be analyzed in the development process for the validation of system elements. The process model for data-driven validation of elements in the system of objectives aids developers in performing such data analyses. The conducted studies show that the basis for an efficient analysis process is a common understanding of the system and the goal of the analysis. Therefore, a template was derived over the course of case studies describing the elements in the system of objectives. The template covers the three descriptive dimensions general information, technical system and data. It allows a comprehensive description of analysis use cases. On average it takes 11 minutes for developers to aggregate all necessary information and consequently fill out the template. An A/B-Test confirmed the comprehensibility and applicability of the template even for developers of different domain knowledge. Through its contribution to a sustainable knowledge management the template provides an added value for the developers for conducting analysis

The Book of Acoustics

The Book of Acoustics was created in collaboration with leading acousticians, neuroscientists and designers. It explores the science of sound and provides guidance for designing with acoustics. Complete with facts, figures, diagrams and expert insight, it is the ideal starting point for architectural and interior design projects and sheds light on the interplay between engineering and aesthetics

Data-driven modelling of the functional level in model-based systems engineering – Optimization of module scopes in modular development

The modelling of the functional level of technical systems can be supported by the analysis of machine usage data. By creating an understanding of the actual use of provided functions of offered machine configurations, the definition of module scopes in modular development can be optimized. Characteristics of specific machine usage can be assigned to physical elements using model-based systems engineering. Analyses on a purely functional system level can thus be placed in context with each other via the connection to physical elements. Consequently, critical elements in the system design can be systematically uncovered

RAD51C – a new human cancer susceptibility gene for sporadic squamous cell carcinoma of the head and neck (HNSCC)

INTRODUCTION: Head and neck squamous cell carcinomas (HNSSCs) are one of the leading causes of cancer-associated death worldwide. Although certain behavioral risk factors are well recognized as tumor promoting, there is very little known about the presence of predisposing germline mutations in HNSCC patients. METHODS: In this study, we analyzed 121 individuals with HNSCCs collected at our institution for germline alterations in the newly identified cancer susceptibility gene RAD51C. RESULTS: Sequencing of all exons and the adjacent introns revealed five distinct heterozygous sequence deviations in RAD51C in seven patients (5.8%). A female patient without any other risk factors carried a germline mutation that disrupted the canonical splice acceptor site of exon 5 (c.706-2A>G). CONCLUSIONS: As there are only a few publications in the literature identifying germline mutations in head and neck cancer patients, our results provide the first indication that paralogs of RAD51, recently described as mutated in breast and ovarian cancer patients, might also be candidates for genetic risk factors in sporadic squamous cell carcinomas of the head and neck

An intronic alteration of the fibroblast growth factor 10 gene causing ALSG-(aplasia of lacrimal and salivary glands) syndrome

<p>Abstract</p> <p>Background</p> <p>A combined aplasia, hypoplasia or atresia of lacrimal points and salivary glands is rarely diagnosed. Those patients suffer from epiphora, xerostomia and severe dental caries. This phenotype represents the autosomal-dominant aplasia of lacrimal and salivary glands syndrome (ALSG). Recently, aberrations of the <it>Fibroblast Growth Factor 10 </it>(<it>FGF10</it>) gene have been identified to be causative for this disorder.</p> <p>Methods</p> <p>We performed a sequence analysis of the <it>FGF10 </it>gene of a patient with ALSG-syndrome and his also affected brother as well as 193 controls. The FGF10 transcript was analyzed using RNA extracted from primary fibroblasts of the patient's mucosa.</p> <p>Results</p> <p>We detected a novel heterozygous sequence variation in intron 2 (c.430-1, G > A) causing the ALSG syndrome. The alteration derogates the regular splice acceptor site and leads to the use of a new splice acceptor site 127 bp upstream of exon 3. The aberration was detected in the genomic DNA derived from two affected brothers, but not in 193 control individuals. Furthermore, no diseased member of the family displayed additional abnormalities that are indicative for the clinically overlapping lacrimo-auriculo-dento-digital syndrome (LADD).</p> <p>Conclusion</p> <p>This family-based approach revealed an intronic variation of the <it>FGF10 </it>gene causing ALSG-syndrome. Our results expand the mutational and clinical spectrum of the ALSG syndrome.</p