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Zusammenfassung Hintergrund Aufgrund des demografischen Wandels ist mit einer steigenden Zahl an Koxarthrosefällen zu rechnen mit entsprechenden Auswirkungen auf das Gesundheitssystem. Ziel der Studie war es, konkretisierte Aussagen zur Versorgungsrealität von Koxarthrosepatienten, inklusive ihrer ambulanten Versorgung und Endoprothesenversorgung zu erhalten. Patienten und Methodik Ausgewertet wurden die Versorgungsdaten von 2,4 Mio. Versicherten der AOK Baden-Württemberg für die Jahre 2007 bis 2016. Altersuntergrenze war 40 Jahre. Die Daten beinhalten den ambulanten und stationären Versorgungssektor. Ergebnisse Altersstandardisiert ergibt sich eine Koxarthroseprävalenz für Frauen ab dem 40. Lebensjahr von 6,18% (95%-KI: ± 0,09%) und für Männer von 6,02% (95%-KI: ± 0,09%). Ab dem 75. Lebensjahr werden die Geschlechtsunterschiede signifikant. Das Maximum für Koxarthrose-Erstdiagnosen findet sich bei den 80- bis 84-Jährigen (Frauen: 1,31%, Männer: 1,16%). Ab dem 85. Lebensjahr weisen 17,4% der Frauen und 16,5% der Männer eine Koxarthrose auf. Das Maximum für Hüft-TEPs unter Koxarthrosepatienten (Frauen: 5,2%, Männer: 4,3%) findet sich bei den 75- bis 79-Jährigen. Nach Erstdiagnose einer Koxarthrose erhält jeder 8. AOK-Versicherte (13,0%) innerhalb des 1. Jahres und jeder 4. (24,8%) innerhalb von 8 Jahren eine Hüft-TEP. Zwischen 2009 und 2016 ist, unabhängig von der Hauptdiagnose, die Häufigkeit von Hüft-TEPs nicht gestiegen. Im Mittel wurden pro 100 000 Versichertenjahre bei Frauen 300,9 und bei Männern 275,8 Hüft-TEP OPs durchgeführt. Ab dem 80. Lebensjahr fällt die Koxarthrose als Hauptdiagnose zurück. Ab 85 weisen mehr als 70% aller Hüft-TEP-Patienten eine Femurfraktur als Hauptdiagnose auf. Nur rund ¾ der Koxarthrosepatienten waren im Jahr vor OP in ambulanter fachärztlicher Betreuung und deutlich weniger als die Hälfte erhielten eine Heilmittelverordnung. Schlussfolgerungen Koxarthrose kommt bis zum 75. Lebensjahr bei Frauen und Männern in etwa gleich häufig vor. Dennoch werden Frauen häufiger operiert. Insgesamt kam es in den letzten 8 Jahren aber nicht zu einem Anstieg der Hüft-TEP-Erstimplantationen. Innerhalb der ersten 8 Jahre nach Erstdiagnose erhalten 24,8% aller Koxarthrosepatienten eine TEP. Die Mehrzahl wird in den ersten 8 Jahren also konservativ behandelt. Im direkten Vergleich zwischen inzidenten und prävalenten Koxarthrosepatienten zeigt sich, dass nach langjähriger therapeutischer Begleitung in den letzten 1 – 2 Jahren vor OP sowohl die fachärztliche Betreuung als auch die Heilmittelverordnung reduziert werden. Eine Neubewertung konservativer Therapiemöglichkeiten im zeitlichen Verlauf erscheint notwendig.

Due to demographic changes an increasing number of hip osteoarthritis can be expected with corresponding effects on the health care system. Hence, the objectives of our study were to obtain substantiated evidence about current medical care situation of hip osteoarthritis patients including outpatient care situation and hip replacement surgery.Overall, the medical care data of 2.4 million insurees of the AOK Baden-Württemberg for the years 2007 to 2016 were analyzed. Lower limit of age was 40 years. The data includes outpatient and inpatient healthcare claims.The age standardized prevalence of hip osteoarthritis in adults aged 40 years or older is 6.18% (95% CI: ± 0.09%) among women and 6.02% (95% CI: ± 0.09%) among men. From the age of 75, sex differences become significant. The maximum number of newly diagnosed cases of hip osteoarthritis (women: 1.31%, men: 1.16%) is found in the 80 - 84-year-olds. From the age of 85, 17.4% of all women and 16.5% of all men show a hip osteoarthritis. The maximum number of hip replacement surgery among osteoarthritis patients (women: 5.2%, men: 4.3%) appears in the 75- to 79-year-olds. After the initial diagnosis of a hip osteoarthritis, every eighth (13.0%) AOK insured person receives a hip replacement surgery within the first year and one in four (24.8%) insurees within 8 years. Irrespective of the main diagnosis, numbers of hip replacement surgery did not increase between 2009 and 2016. On average, 300.9 (women) and 275.8 (men) hip replacement surgeries were performed per 100 000 insured years. From the age of 80, hip osteoarthritis drops back as the main diagnosis fur surgery. Consequently, from the age of 85 more than 70% of all hip replacement patients show a femoral fracture as main diagnosis. Only about ¾ of the hip osteoarthritis patients were in outpatient specialist care in the year before surgery, and far less than half of hip osteoarthritis patients received a referral to physiotherapy.Osteoarthritis of the hip occurs approximately equally often in women and men up to the age of 75 years. Nevertheless, women underwent surgery more frequently. Overall, the number of hip replacement surgery has not increased in the last eight years. Within the first eight years after initial diagnosis of hip osteoarthritis 24.8% of all patients receive a hip TEP. Hence, the majority of patients is treated conservatively in the first eight years. A direct comparison between incidence and prevalent hip osteoarthritis patients reveals that after many years of therapeutic care in the last 1 - 2 years prior to surgery, both the specialist care as well as the referral to physiotherapy are reduced. A reassessment of conservative treatment options over time seems to be necessary.Aufgrund des demografischen Wandels ist mit einer steigenden Zahl an Koxarthrosefällen zu rechnen mit entsprechenden Auswirkungen auf das Gesundheitssystem. Ziel der Studie war es, konkretisierte Aussagen zur Versorgungsrealität von Koxarthrosepatienten, inklusive ihrer ambulanten Versorgung und Endoprothesenversorgung zu erhalten.Ausgewertet wurden die Versorgungsdaten von 2,4 Mio. Versicherten der AOK Baden-Württemberg für die Jahre 2007 bis 2016. Altersuntergrenze war 40 Jahre. Die Daten beinhalten den ambulanten und stationären Versorgungssektor.Altersstandardisiert ergibt sich eine Koxarthroseprävalenz für Frauen ab dem 40. Lebensjahr von 6,18% (95%-KI: ± 0,09%) und für Männer von 6,02% (95%-KI: ± 0,09%). Ab dem 75. Lebensjahr werden die Geschlechtsunterschiede signifikant. Das Maximum für Koxarthrose-Erstdiagnosen findet sich bei den 80- bis 84-Jährigen (Frauen: 1,31%, Männer: 1,16%). Ab dem 85. Lebensjahr weisen 17,4% der Frauen und 16,5% der Männer eine Koxarthrose auf. Das Maximum für Hüft-TEPs unter Koxarthrosepatienten (Frauen: 5,2%, Männer: 4,3%) findet sich bei den 75- bis 79-Jährigen. Nach Erstdiagnose einer Koxarthrose erhält jeder 8. AOK-Versicherte (13,0%) innerhalb des 1. Jahres und jeder 4. (24,8%) innerhalb von 8 Jahren eine Hüft-TEP. Zwischen 2009 und 2016 ist, unabhängig von der Hauptdiagnose, die Häufigkeit von Hüft-TEPs nicht gestiegen. Im Mittel wurden pro 100 000 Versichertenjahre bei Frauen 300,9 und bei Männern 275,8 Hüft-TEP OPs durchgeführt. Ab dem 80. Lebensjahr fällt die Koxarthrose als Hauptdiagnose zurück. Ab 85 weisen mehr als 70% aller Hüft-TEP-Patienten eine Femurfraktur als Hauptdiagnose auf. Nur rund ¾ der Koxarthrosepatienten waren im Jahr vor OP in ambulanter fachärztlicher Betreuung und deutlich weniger als die Hälfte erhielten eine Heilmittelverordnung.Koxarthrose kommt bis zum 75. Lebensjahr bei Frauen und Männern in etwa gleich häufig vor. Dennoch werden Frauen häufiger operiert. Insgesamt kam es in den letzten 8 Jahren aber nicht zu einem Anstieg der Hüft-TEP-Erstimplantationen. Innerhalb der ersten 8 Jahre nach Erstdiagnose erhalten 24,8% aller Koxarthrosepatienten eine TEP. Die Mehrzahl wird in den ersten 8 Jahren also konservativ behandelt. Im direkten Vergleich zwischen inzidenten und prävalenten Koxarthrosepatienten zeigt sich, dass nach langjähriger therapeutischer Begleitung in den letzten 1 – 2 Jahren vor OP sowohl die fachärztliche Betreuung als auch die Heilmittelverordnung reduziert werden. Eine Neubewertung konservativer Therapiemöglichkeiten im zeitlichen Verlauf erscheint notwendig.

Objective Follistatin (FS) is the specific binding protein of activin and expression of both factors is regulated by inflammatory agents. Therefore, FS concentrations were determined in cerebrospinal fluid (CSF) of patients with bacterial and viral meningitis or multiple sclerosis (MS), as well as in the CSF of patients without meningial inflammation or autoimmune diseases. Furthermore, a mouse pneumococcal meningitis model was used to localise the cellular sources of FS in brains of normal and meningitic mice. Methods FS concentrations in CSF were determined by ELISA; FS in mice was localised by in situ hybridisation and immunohistochemistry. Results FS concentrations were > or =0.4 microg/l in 22 of 66 CSF samples of meningitis patients versus 2 of 27 CSF samples from patients with multiple sclerosis (P Conclusions The concentration of FS in humans is elevated during meningitis. In some patients the increase is caused by a release of FS from brain into CSF. Data from the mouse meningitis model suggest that increased CSF concentrations of FS in meningitis appear not to be accompanied by an elevated number of cells containing FS mRNA or protein in the brain.

OBJECTIVE: The relation of activins (dimers of the beta-subunits of inhibin) and follistatin (FS) (their binding protein) affect the growth and differentiation of many cell types. Activin- and FS-mRNAs show a widespread co-expression throughout the organism, indicating an essential role for the FS/activin system in diverse physiological processes. The present study was performed to investigate FS-, activin betaA-, and activin beta B-mRNA expression in porcine tissues and to compare the relative mRNA tissue distribution by a newly developed multiplex S1 nuclease protection assay. METHODS: Twenty micrograms total RNA from different porcine tissues were subjected to multiplex S1 analysis. Specific mRNA expression was determined by measurements of optical densities on autoradiographs. RESULTS: Activin beta A-mRNA expression was abundant in the ovary, adrenal gland, fat, vein, artery and uterus, activin beta B-mRNA was highly expressed in the ovary, pituitary, uterus, placenta, aorta and cerebellum. FS-mRNA showed a widespread expression with high levels in ovary, uterus, cerebellum, placenta and fat. The comparison of relative activin beta A-, activin beta B- and FS-mRNA expression within a certain tissue showed a predominance of activin beta A-mRNA in the adrenal gland, fat, artery, spinal cord, cerebrum and colon and of activin beta B-m RNA in pituitary, testis and placenta, while FS-mRNA levels exceeded those of activin subunits in epididymis, liver, lymphoid tissue, muscle, intestine, cerebellum, ovary and uterus. CONCLUSIONS: The presented data provide an overview of FS-, activin beta A-, and activin beta B-mRNA steady state levels in porcine tissues.

Follistatin (FS) is the specific binding protein of activin; it has a broad tissue distribution and is also found in serum. The ovary has the highest level of FS expression, but ovariectomy does not cause a permanent reduction in the serum FS level. Therefore, the source of FS in serum is still elusive. As a regulatable, nongonadal source of serum FS could influence ovarian and pituitary-derived hormone secretion and thus reproductive function, we searched for a source of extragonadal FS expression that might contribute to the FS protein level in serum. We found that endothelial cells from blood vessels express FS messenger RNA (mRNA) and protein; therefore, we studied the regulation of steady state levels of FS mRNA in porcine endothelial cells from aorta (AEC) and brain microvessels (BMVEC) in tissue culture. For detection of FS mRNA, a specific 32P-radiolabeled antisense probe and a S1-nuclease protection assay were used. FS steady state levels of AEC decreased with time in culture, i.e. postconfluent AEC had lower FS mRNA levels than confluent cultures, which, in turn, had lower FS mRNA levels than subconfluent cell cultures. FS mRNA levels in AEC were induced by increasing concentrations of FCS and stimulated by 30 micrograms/ml endothelial cell growth supplement. FS mRNA levels in AEC and BMVEC increased approximately 20-fold within 4 h during incubation of the cells with 100 nM phorbol 12-myristate, 13-acetate, whereas 0.5 nmol/ml forskolin tested in AEC for between 4-48 h had no significant effect. Furthermore, 0.1 microM ocadaic acid, an inhibitor of serine/threonine phosphatases 1 and 2A, caused a significant increase in FS mRNA levels. FS mRNA levels in AEC were not significantly affected by various concentrations of porcine FSH, epidermal growth factor, or retinoic acid for between 4-48 h. Treatment of the cells with 0.01-10 micrograms/ml bacterial lipopolysaccharides (LPS) caused a dose-dependent increase (up to 10-fold) in FS mRNA steady state level in AEC, whereas 1-1000 nM RU 28362, a synthetic glucocorticoid, inhibited FS mRNA steady state levels in a dose-dependent manner. The induction of FS mRNA with 1 microgram/ml LPS was completely blocked by 100 nM RU 28362, and the stimulatory effects of LPS were only visible after 4 h of treatment, not after 24 or 48 h. The same effects were observed with BMVEC. We, furthermore, analyzed FS protein secretion of AEC by Western blotting and demonstrated that FS proteins were secreted into the culture medium upon stimulation with LPS. None of these treatments had an obvious effect on the ratio of the two different forms of FS mRNA (FS 344:FS 317). Besides the expression of FS mRNA in AEC and BMVEC, FS mRNA is also expressed in uncultured plexus choroideus epithel and meninges, and FS protein is found in human cerebrospinal fluid. From this study it is concluded that 1) endothelial cells from different tissues produce FS mRNA; 2) the FS mRNA levels of AEC and BMVEC are subjected to regulation by FCS, endothelial cell growth supplement, bacterial LPS, and the glucocorticoid RU 28362; 3) phosphatases and the protein kinase C-dependent, but not the protein kinase A-dependent, pathway are involved in regulating the steady state levels of FS mRNA in AEC and BMVEC; and 4) endothelial cells produce and secrete FS protein and are thus a likely source of FS in serum.

The Collaborative Computing Project for NMR (CCPN) has build a software framework consisting of the CCPN data model (with APIs) for NMR related data, the CcpNmr Analysis program and additional tools like CcpNmr FormatConverter. The open architecture allows for the integration of external software to extend the abilities of the CCPN framework with additional calculation methods. Recently, we have carried out the first steps for integrating our software Computer Simulation of Molecular Structures (COSMOS) into the CCPN framework. The COSMOS-NMR force field unites quantum chemical routines for the calculation of molecular properties with a molecular mechanics force field yielding the relative molecular energies. COSMOS-NMR allows introducing NMR parameters as constraints into molecular mechanics calculations. The resulting infrastructure will be made available for the NMR community. As a first application we have tested the evaluation of calculated protein structures using COSMOS-derived 13C Cα and Cβ chemical shifts. In this paper we give an overview of the methodology and a roadmap for future developments and applications.

Das Lernen mit didaktischen Medien im digitalen Zeitalter soll in Lernwelten und Lernumgebungen stattfinden. Es soll »eigenaktiv, konstruktiv und kommunikativ « sein (van Luck 1996: 6). So oder ahnlich lauten seit etlichen Jahren die Anforderungen der Fach-und Mediendidaktiker an die Gestalter und an die Gestaltung von Lernsoftware. Auch Rolf Schulmeister pladiert fur mehr offene Lernumgebungen, die einen Lernanlass oder einen Rahmen fur den eigentlichen Lernprozess setzen sollen (Schulmeister 2005: 43). Doch wie sollen die Metaphern der Lernumgebungen und -welten mit den Konnotationen Offenheit, Weite und Bewegungsfreiheit in kommerzieller Lernsoftware fur privates und schulisches Lernen praktisch umgesetzt werden? Was heist in diesem Kontext eigentlich eigenaktiv, konstruktiv, kommunikativ und offen? Diese Anforderungen sind in der Vergangenheit von den Entwicklern von Lernsoftware und deren Auftraggebern entweder weitgehend ignoriert oder hochst unterschiedlich interpretiert worden.

OpusIB is an Opteron based cluster system with InfiniBand interconnect. Grid middleware provide the integration into CampusGrid and D-Grid projects. Mentionable details of hardware and software equipment as well as configuration of the cluster will be introduced. Performance measurements show that InfiniBand is not only well suited for message-passing based parallel applications but also competitive as transport layer for data access in shared cluster file systems or high throughput computing.

A central idea of Grid Computing is the virtualization of heterogeneous resources. To meet this challenge the Institute for Scientific Computing (IWR), has started the project CampusGrid. Its medium term goal is to provide a seamless IT environment supporting the on-site research activities in Physics, Bioinformatics, Nanotechnology and Meteorology. The environment will include all kinds of HPC resources: vector computers, shared memory SMP servers and clusters of commodity components, InfiniBand-Clusters as well as a shared high-performance SAN storage solution and a global file system. The paper shows the ideas, the test-bed and informs about the current project status and scheduled development tasks. This is associated with reports on other activities in the fields of Grid computing and high performance computing at IWR and D-Grid.

The sections in this article are 1 History 2 Basic Raster Graphics Architecture 3 Parallel Raster Graphics Architectures 4 Special Purpose Raster Graphics Architectures Keywords: graphics pipeline; frame buffer memories; video memory; video processor; display processor; geometry and rasterization subsystems; parallel vs. pipelined subsystems; object and image parallelism; special-purpose architectures

Compared with b-lactam antibiotics, rifampin releases smaller quantities of proinflammatory cell wall products from Streptococcus pneumoniae in vitro. Mice infected intracerebrally with S. pneumoniae were treated subcutaneously with 2-mg doses of rifampin or ceftriaxone ( each) every 12 h for 3 days and then observed for another 3 days. Rifampin reduced n 5 43 overall mortality from 49% to 26% ( ). Kaplan-Meyer analysis revealed a substantial P 5 .04 reduction of mortality during the first 24 h in mice receiving rifampin (difference in survival time: ). Eight h after receiving a single 2-mg dose of rifampin or ceftriaxone, rifampinP 5 .007 treated mice had lower serum and cerebrospinal fluid concentrations of lipoteichoic and teichoic acids than did ceftriaxone-treated mice (median serum level: !0.5 vs. 27.0 ng/mL, P 5 ; median cerebrospinal fluid level of pooled specimens: 97.5 vs. 206.0 ng/mL). Thus, the .02 use of rifampin appears promising for reducing the release of proinflammatory bacterial components and decreasing early mortality in bacterial meningitis. Despite effective antibiotic therapy, bacterial meningitis is still associated with high rates of mortality and permanent sequelae in children and adults. In 12 of 37 autopsy cases studied at our institution, severe brain edema with transtentorial or cerebellar herniation (or both) was the cause of death. Compounds of the cell wall of gram-positive and gram-negative bacteria (endotoxin, peptidoglycans, and lipoteichoic acid and teichoic acid [LTA-TA]) can release proinflammatory cytokines, induce meningeal inflammation, increase intracranial pressure, and cause brain edema in experimental meningitis [1‐4]. The release of these components into cerebrospinal fluid (CSF) during bacterial lysis by b-lactam antibiotics causes a burst of meningeal inflammation after the initiation of antibiotic therapy [5‐8]. In vitro, rifampin and other bactericidal antibacterials, which act by inhibiting protein synthesis, released substantially smaller quantities of proinflammatory LTA-TA than did b-lactam antibiotics [9]. Furthermore, rifampin can activate the glucocorticoid receptor, thereby functioning as an immunodepressor [10]. Since the brisk inflammatory response after the initiation of therapy with antibacterials currently used for meningitis may contribute to early mortality and long-term sequelae, we compared the effects of rifampin with those of ceftriaxone on mor

Brush provides an interactive environment for the real-time visualization and inspection of very large mechanical and architectural CAD databases. It supports immersive and non-immersive virtual reality walkthrough applications (for example, when validating or demonstrating to a customer an architectural concept) and detailed design reviews of complex mechanical assemblies such as engines, plants, airplanes, or ships.

To reduce the cost of correcting design errors, assemblies of mechanical parts are modeled using CAD systems and verified electronically before the designs are sent to manufacturing. Shaded images are insufficient for examining the internal structures of assemblies and for detecting interferences. Thus, designers must rely on expensive numerical techniques that compute geometric representations of cross-sections and of intersections of solids. The solid-clipping approach presented here bypasses these geometric calculations and offers realtime rendering of cross-sections and interferences for solids represented by their facetted boundaries. In its simplest form, the technique is supported by contemporary highend graphics workstations. Its variations, independently developed elsewhere, have already been demonstrated. Our implementation is based on the concept of a cutvolume interactively manipulated to remove obstructing portions of the assembly and reveal its internal structure. For clarity, faces of the cut-volume which intersect a single solid are hatched and shaded with the color of that solid. Interference areas between two or more solids are highlighted. Furthermore, to help users find the first occurrence of an interference along a search direction, we have developed an adaptive subdivision search based on a projective approach which guarantees a sufficient condition for object disjointness. The additional performance cost for solid-clipping and interference highlighting is comparable to the standard rendering cost. An efficient implementation of the disjointness test requires a minor extension of the graphics functions currently supported on commercial hardware.

We provide an overview of existing strategies which compensate for the deterioration of convergence of minimum residual (MR) Krylov subspace methods due to restarting. We evaluate the popular practice of using nearly invariant subspaces to either augment Krylov subspaces or to construct preconditioners which invert on these subspaces. In the case where these spaces are exactly invariant, the augmentation approach is shown to be superior. We further show how a strategy recently introduced by de Sturler for truncating the approximation space of an MR method can be interpreted as a controlled loosening of the condition for global MR approximation based on the canonical angles between subspaces. For the special case of Krylov subspace methods, we give a concise derivation of the role of Ritz and harmonic Ritz values and vectors in the polynomial description of Krylov spaces as well as of the use of the implicitly updated Arnoldi method for manipulating Krylov spaces.

Trotz einer Vielzahl von Standorttheorien, bei denen ausnahmslos die Transportkosten eine wesentliche Rolle spielen, und trotz der Bedeutung, die dieses Problem angesichts der gewaltigen Summen hat, die in einzelnen Unternehmungen und in der Wirtschaft insgesamt als Transportkosten anfallen, ist bisher eine befriedigende Antwort zu diesem Thema weder von der Theorie noch von der Praxis gegeben worden. In der theoretischen Durcharbeitung geht die eigentliche Problematik in der Regel in der Vielzahl der Pramissen unter, wahrend in der Praxis, von Ausnahmen abgesehen, den Vertriebskosten nicht die ihrer Bedeutung entsprechende Beachtung geschenkt wird. Bei den umfangreichen Rationalisierungsreserven, die fur die Unternehmungen in einer systematischen Durcharbeitung der Transportkosten und damit speziell der Frage der Standortbeeinflussung liegen, ist jedoch angesichts des zunehmenden Wettbewerbes damit zu rechnen, das die Praxis diesem Themenbereich in der Zukunft verstarkte Aufmerksamkeit schenken wird.