Die N34S-SPINK1-Mutation und Mutationen des CFTR-Gens als Risikofaktoren der chronischen Pankreatitis - Eine retrospektiv epidemiologische Studie zum Krankheitsverlauf

Ausgangslage: Die genetischen Grundlagen der chronischen Pankreatitis sind zum heutigen Zeitpunkt nur unzureichend erforscht. Mutationen im Gen des Serinprotease-Inhibitors Kazal Type 1 (SPINK1) und heterozygote Mutationen im CFTR-Gen wurden in zahlreichen Untersuchungen gehäuft bei Patienten mit chronischer Pankreatitis nachgewiesen. Methodik: Es wurden retrospektiv anhand der Daten der Pankcourse Studie (2004-2007) Untersuchungen bei Patienten mit chronischer Pankreatitis zur Häufigkeit von SPINK1- und CFTR-Mutationen sowie zum Manifestationszeitpunkt der Erkrankung durchgeführt. In Fall-Kontroll-Analysen wurde untersucht, ob sich Unterschiede in den jeweiligen Krankheitsverläufen nachweisen lassen. Ergebnisse: Eine heterozygote SPINK1-Mutation (N34S) konnte bei 11,5% und eine CFTR-Mutationen bei 24% der untersuchten Patienten nachgewiesen werden. Bei Patienten mit SPINK1-Mutation fand sich im Gegensatz zu Patienten mit CFTR-Mutation eine signifikant frühere Krankheitsmanifestation als bei Patienten ohne Mutationsnachweis. Patienten mit SPINK1-Mutation mussten zudem seltener und später operiert werden als Patienten ohne Mutation. Bei Patienten mit CFTR-Mutation zeigte sich ein signifikant früheres Auftreten von Stenosierungen und Konkrementen des D. pancreaticus im Vergleich zur Kontrollgruppe. Schlussfolgerung: Die ätiologische Bedeutung von SPINK1- und CFTR-Mutationen konnte bestätigt werden. Es fanden sich einzelne Hinweise auf einen durch die jeweilige Mutation verursachten charakteristischen Krankheitsverlauf, was durch weitergehende Untersuchungen bestätigt werden muss

On the influence of material properties in sheet bending processes

In order to achieve the high performance and precision requirements of modern sheet bending processes, an appropriate implementation of material properties is essential. Experiments have shown that even variations within a lot of a specific material play an important role. For this sake, detailed knowledge of the influence of the specific properties like flow curve, rolling direction, strain rate, anisotropy etc. is required. In a first step, tension tests have been performed for some materials which are frequently used in industrial applications. In order to simulate the sheet bending process, advanced simulation models have been implemented. Detailed parameter studies have been performed, and the essential parameters and their influence on the bending process have been found out. The results have been compared to measurement results of the bending process

Comparison of Eye Movement Indices of Multiple-Choice Images in Aphasia Batteries, Clipart Images and Images Designed to Control for Physical and Semantic Stimulus Properties

Careful design of images of multiple-choice tasks in aphasia assessment is critical to assessment validity. An objective way to evaluate multiple-choice image design is to track eye movements as individuals view sets of images without verbal stimuli. The degree of disproportionate visual attention across images indicates a greater risk to validity of test items. Nineteen adults’ eye movements were recorded as they looked at 64 image sets: 22 sets with well designed physical and semantic stimulus properties, 22 sets of clipart images and 20 sets of images from published aphasia tests. Variation of disproportionate looking among image types is discussed

Hochschulpolitik als Arbeitsmarktpolitik: Vorschläge zu einer beschäftigungsorientierten Hochschul- und Studienreform

Dieser Beitrag gibt einen Überblick über wichtige Themen der gegenwärtigen Diskussion zum Verhältnis von Hochschulen, Studium und Arbeitsmarkt und entwickelt auf dieser Basis eine Reihe von Positionen und Reformvorschlägen, die Anstöße für die weitere hochschulpolitische Auseinandersetzung geben sollen. Es geht aus von Veränderungen in den für Arbeitsmärkte und Erwerbstätigkeit maßgeblichen gesellschaftlichen Rahmenbedingungen und in den Erwartungen der Wirtschaft und beschäftigt sich vor diesem Hintergrund eingehender mit der Rolle von Hochschulen und Wissenschaft in der Arbeitswelt von morgen. -- This paper surveys central issues in the current discussion on the relationship between universities, academic studies, and the labor market. On this basis, a series of positions and recommendations for reform are put forward as contributions the continuing debate on university policy. The starting point for this are both changes in the social framework that crucially influence developments in labor markets and employment, and changing expectations within the economy. Against this backdrop, the paper deals intensively with the role of academia, scholarly study and science in the future world of work.

Identification of binding proteins for cholesterol absorption inhibitors as components of the intestinal cholesterol transporter

AbstractTo identify protein components of the intestinal cholesterol transporter, rabbit small intestinal brush border membrane vesicles were submitted to photoaffinity labeling using photoreactive derivatives of 2-azetidinone cholesterol absorption inhibitors. An integral membrane protein of Mr 145.3±7.5 kDa was specifically labeled in brush border membrane vesicles from rabbit jejunum and ileum. Its labeling was concentration-dependently inhibited by the presence of cholesterol absorption inhibitors whereas bile acids, D-glucose, fatty acids or cephalexin had no effect. The inhibitory potency of 2-azetidinones to inhibit photolabeling of the 145 kDa protein correlated with their in vivo activity to inhibit intestinal cholesterol absorption. These results suggest that an integral membrane protein of Mr 145 kDa is (a component of) the cholesterol absorption system in the brush border membrane of small intestinal enterocytes

Amicus Brief: Kumho Tire v. Carmichael

This brief addresses the issue of jury performance and jury responses to expert testimony. It reviews and summaries a substantial body of research evidence about jury behavior that has been produced over the past quarter century. The great weight of that evidence challenges the view that jurors abdicate their responsibilities as fact finders when faced with expert evidence or that they are pro-plaintiff, anti-defendant, and anti-business. The Petitioners and amici on behalf of petitioners make a number of overlapping, but empirically unsupported, assertions about jury behavior in response to expert testimony, namely that juries are frequently incapable of critically evaluation expert testimony, are easily confused, give inordinate weight to expert testimony, are awed by science, defer to the opinions of unreliable experts, and, implicitly, that in civil trials juries tilt in favor of plaintiffs and against corporations

In vivo biofunctional evaluation of hydrogels for disc regeneration

Purpose Regenerative strategies aim to restore the original biofunctionality of the intervertebral disc. Different biomaterials are available, which might support disc regeneration. In the present study, the prospects of success of two hydrogels functionalized with anti-angiogenic peptides and seeded with bone marrow derived mononuclear cells (BMC), respectively, were investigated in an ovine nucleotomy model. Methods In a one-step procedure iliac crest aspirates were harvested and, subsequently, separated BMC were seeded on hydrogels and implanted into the ovine disc. For the cell-seeded approach a hyaluronic acid-based hydrogel was used. The anti-angiogenic potential of newly developed VEGF-blockers was investigated on ionically crosslinked metacrylated gellan gum hydrogels. Untreated discs served as nucleotomy controls. 24 adult merino sheep were used. After 6 weeks histological, after 12 weeks histological and biomechanical analyses were conducted. Results Biomechanical tests revealed no differences between any of the implanted and nucleotomized discs. All implanted discs significantly degenerated compared to intact discs. In contrast, there was no marked difference between implanted and nucleotomized discs. In tendency, albeit not significant, degeneration score and disc height index deteriorated for all but not for the cell-seeded hydrogels from 6 to 12 weeks. Cell-seeded hydrogels slightly decelerated degeneration. Conclusions None of the hydrogel configurations was able to regenerate biofunctionality of the intervertebral disc. This might presumably be caused by hydrogel extrusion. Great importance should be given to the development of annulus sealants, which effectively exploit the potential of (cell-seeded) hydrogels for biological disc regeneration and restoration of intervertebral disc functioningThis work was supported by the EU-project Disc Regeneration (NMP3-LA-2008-213904). Technical assistance of Iris Baum and the whole animal surgery team of the Institute of Orthopaedic Research and Biomechanics, Ulm, are gratefully acknowledged. DDAHA hydrogels were kindly provided by Cristina Longinotti (DDAHA, Anika Therapeutics, Abano Therme, Italy)