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Background Titanium and titanium alloys are widely used for fabrication of dental implants. Since the material composition and the surface topography of a biomaterial play a fundamental role in osseointegration, various chemical and physical surface modifications have been developed to improve osseous healing. Zirconia-based implants were introduced into dental implantology as an altenative to titanium implants. Zirconia seems to be a suitable implant material because of its tooth-like colour, its mechanical properties and its biocompatibility. As the osseointegration of zirconia implants has not been extensively investigated, the aim of this study was to compare the osseous healing of zirconia implants with titanium implants which have a roughened surface but otherwise similar implant geometries. Methods Forty-eight zirconia and titanium implants were introduced into the tibia of 12 minipigs. After 1, 4 or 12 weeks, animals were sacrificed and specimens containing the implants were examined in terms of histological and ultrastructural techniques. Results Histological results showed direct bone contact on the zirconia and titanium surfaces. Bone implant contact as measured by histomorphometry was slightly better on titanium than on zirconia surfaces. However, a statistically significant difference between the two groups was not observed. Conclusion The results demonstrated that zirconia implants with modified surfaces result in an osseointegration which is comparable with that of titanium implants.
Feucht- und Nasswiesen mit intaktem Wasserhaushalt, die früher typisch für Niederungen an Flüssen und Seen in Norddeutschland waren, sind in den letzten Jahrzehnten durch Entwässerung von Niederungen sowie durch Veränderungen in der Nutzungsintensität stark in ihrem Bestand zurückgegangen (IRMLER ET AL. 1998). Sowohl eine Nutzungsintensivierung mit verstärkter Düngung, erhöhter Viehdichte und Schnitthäufigkeit, Vorverlegung der ersten Mahd als auch die Nutzungsaufgabe mit übermäßiger Extensivierung und Wiedervernässung durch überhöhte Stauhaltung sind problematisch für den Erhalt artenreicher Feuchtwiesen (Calthion palustris), die ursprünglich durch eine traditionelle Zweischnittnutzung entstanden sind (HELLBERG ET AL. 2003). Artenreiches Feuchtgrünland hat sich gegenwärtig vorwiegend in kleinen, schwer zu entwässernden Niederungen wie z.B. im Schwentinetal mit seinen nassen und tiefen Niedermoorböden, die sich von jeher einer intensiven landwirtschaftlichen Nutzung entzogen haben, großflächig erhalten können (SCHUHMANN 2003). Im Rahmen eines Naturschutzprojektes zur Extensivierung von Grünland wurde 1986-1988 die Insektenfauna im Schwentinetal von Feucht- und Nasswiesen auf mäßig entwässerten Niedermoorböden, mit unterschiedlicher Bewirtschaftungsintensität untersucht. Hauptkriterien waren der Einfluss von Grundwasserpegelständen und Beweidung auf die Abundanz der Langbein- und Tanzfliegen sowie die Verteilung der ökologischen Artengruppen auf die einzelnen Grünlandtypen. Weitere Kriterien beinhalteten Dominanz- und Geschlechtsverhältnis, Phänologie und den Gefährdungsstatus der Arten.
Proton emission in relativistic nuclear collisions is examined for events of low and high multiplicity, corresponding to large and small impact parameters. Peripheral reactions exhibit distributions of protons in agreement with spectator-participant decay modes. Central collisions of equal-size nuclei are dominated by the formation and decay of a fireball system. Central collisions of light projectiles with heavy targets exhibit an enhancement in sideward emission which is predicted by recent hydrodynamical calculations.
Inclusive energy spectra of protons, deuterons, and tritons were measured with a telescope of silicon and germanium detectors with a detection range for proton energies up to 200 MeV. Fifteen sets of data were taken using projectiles ranging from protons to 40Ar on targets from 27Al to 238U at bombarding energies from 240 MeV/nucleon to 2.1 GeV/nucleon. Particular attention was paid to the absolute normalization of the cross sections. For three previously reported reactions, He fragment cross sections have been corrected and are presented. To facilitate a comparison with theory the sum of nucleonic charges emitted as protons plus composite particles was estimated and is presented as a function of fragment energy per nucleon in the interval from 15 to 200 MeV/nucleon. For low-energy fragments at forward angles the protons account for only 25% of the nucleonic charges. The equal mass 40Ar plus Ca systems were examined in the center of mass. Here at 0.4 GeV/nucleon 40Ar plus Ca the proton spectra appear to be nearly isotropic in the center of mass over the region measured. Comparisons of some data with firestreak, cascade, and fluid dynamics models indicate a failure of the first and a fair agreement with the latter two. In addition, associated fast charged particle multiplicities (where the particles had energies larger than 25 MeV/nucleon) and azimuthal correlations were measured with an 80 counter array of plastic scintillators. It was found that the associated multiplicities were a smooth function of the total kinetic energy of the projectile. NUCLEAR REACTIONS U(20Ne,X), E / A=240 MeV/nucleon; U(40Ar,X), Ca(40Ar,X), U(20Ne,X), Au(20Ne,X), Ag(20Ne,X), Al(20Ne,X), U(4He,X), Al(4He,X), E / A=390 MeV/nucleon; U(40Ar,X), Ca(40Ar,X), U(20Ne,X), U(4He,X), U(p,X), E / A=1.04 GeV/nucleon; U(20Ne,X), E / A=2.1 GeV/nucleon; measured sigma (E, theta ), X=p,d,t.
Pion-production cross sections have been measured for the reaction 40Ar+40Ca--> pi ++X at a laboratory energy of 1.05 GeV/nucleon. A maximum in the pi + cross section occurs at mid-rapidity, which is anomalous relative to p+p and p+nucleus reactions and compared to many other heavy-ion reactions. Calculations based on cascade and thermal models fail to fit the data.
A simple model is proposed for the emission of nucleons with velocities intermediate between those of the target and projectile. In this model, the nucleons which are mutually swept out from the target and projectile form a hot quasiequilibrated fireball which decays as an ideal gas. The overall features of the proton-inclusive spectra from 250- and 400-MeV/nucleon 20Ne ions and 400-MeV/nucleon 4He ions interacting with uranium are fitted without any adjustable parameters.
Pion production and charged-particle multiplicity selection in relativistic nuclear collisions
(1982)
Spectra of positive pions with energies of 15-95 MeV were measured for high energy proton, 4He, 20Ne, and 40Ar bombardments of targets of 27Al, 40Ca, 107,109Ag, 197Au, and 238U. A Si-Ge telescope was used to identify charged pions by dE / dx-E and, in addition, stopped pi + were tagged by the subsequent muon decay. In all, results for 14 target-projectile combinations are presented to study the dependence of pion emission patterns on the bombarding energy (from E / A=0.25 to 2.1 GeV) and on the target and the projectile masses. In addition, associated charged-particle multiplicities were measured in an 80-paddle array of plastic scintillators, and used to make impact parameter selections on the pion-inclusive data. NUCLEAR REACTIONS U(20Ne, pi +), E / A=250 MeV; U(40Ar, pi +), Ca(40Ar, pi +), U(20Ne, pi +), Au(20Ne, pi +), Ag(20Ne, pi +), Al(20Ne, pi +), U(4He, pi +), Al(4He, pi +). E / A=400 MeV; Ca(40Ar, pi +), U(20Ne, pi +), U(4He, pi +), U(p, pi +), E / A=1.05), GeV; U(20Ne, pi +), E / A=2.1 GeV; measured sigma (E, theta ), inclusive and selected on associated charged-particle multiplicity.
The energy spectra of protons and light nuclei produced by the interaction of 4He and 20Ne projectiles with Al and U targets have been investigated at incident energies ranging from 0.25 to 2.1 GeV per nucleon. Single fragment inclusive spectra have been obtained at angles between 25° and 150°, in the energy range from 30 to 150 MeV/nucleon. The multiplicity of intermediate and high energy charged particles was determined in coincidence with the measured fragments. In a separate study, fragment spectra were obtained in the evaporation energy range from 12C and 20Ne bombardment of uranium. We observe structureless, exponentially decaying spectra throughout the range of studied fragment masses. There is evidence for two major classes of fragments; one with emission at intermediate temperature from a system moving slowly in the lab frame, and the other with high temperature emission from a system propagating at a velocity intermediate between target and projectile. The high energy proton spectra are fairly well reproduced by a nuclear fireball model based on simple geometrical, kinematical, and statistical assumptions. Light cluster emission is also discussed in the framework of statistical models. NUCLEAR REACTIONS U(20Ne,X), E=250 MeV/nucl.; U(20Ne,X), U(α,X) E=400 MeV/nucl.; U(20Ne,X), Al(20Ne,X), E=2.1 GeV/nucl.; measured σ(E,θ), X=p, d, t, 3He,4He. U(20Ne,X), U(α,X), E=400 MeV/nucl.; U(20Ne,X), E=2.1 GeV/nucl.; measured σ(E, θ), Li to O. U(20Ne,X), U(12C,X), E=2.1 GeV/nucl.; measured σ(E, 90°), 4He to B. Nuclear fireballs, coalescence, thermodynamics of light nuclei production.
Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group’s cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The “ex-novo” occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies’ positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.
Anhand morphologischer und struktureller Befunde werden die Glieder der Rehburger Eisrandlage als Stauchendmoränen gedeutet. Die Aufstauchung erfolgte im Zuge eines kontinuierlichen Eisvorstoßes während der Saale-Eiszeit (Drenthe-Stadium) durch sog. Stirnoder Frontalstauchung. Es wird ein Modell dieser Stauchung vorgestellt ("Modell Kellenberg"). Als Steuerungsfaktoren der Stauchungsprozesse werden angenommen: 1. das dynamische Verhalten des Inlandeises (Vorschub, Belastungsdruck); 2. die bodenmechanischen Eigenschaften des gestauchten Substrates (Plastizität, Scherfestigkeit, Permafrost-Zementierung, Schmiermitteleffekt); 3. das präexistente Relief (Widerlager- oder Rampeneffekt). Nach der Aufstauchung wurde die Stau ehzone vom Eis der "Hamelner Phase" überfahren und in unbekanntem Ausmaß erniedrigt (eingerumpft). Im periglaziären Milieu der späten Saale-Eiszeit (Warthe-Stadium) und der Weichsel-Eiszeit erfolgte durch selektive Erosion eine Akzentuierung der Mesoformen (Bildung von Härtlingsrükken); gleichzeitig wurde die Prägnanz der Makroformen durch das gegenläufige Nebeneinander von subaerischer Abtragung auf den Höhenrücken und periglazialablualer Aufschüttung in den Niederungen (Talsande) verringert.
Background: Tuberous sclerosis complex (TSC), a multisystem genetic disorder, affects many organs and systems, characterized by benign growths. This German multicenter study estimated the disease-specific costs and cost-driving factors associated with various organ manifestations in TSC patients. Methods: A validated, three-month, retrospective questionnaire was administered to assess the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket, and nursing care-level costs, completed by caregivers of patients with TSC throughout Germany. Results: The caregivers of 184 patients (mean age 9.8 ± 5.3 years, range 0.7–21.8 years) submitted questionnaires. The reported TSC disease manifestations included epilepsy (92%), skin disorders (86%), structural brain disorders (83%), heart and circulatory system disorders (67%), kidney and urinary tract disorders (53%), and psychiatric disorders (51%). Genetic variations in TSC2 were reported in 46% of patients, whereas 14% were reported in TSC1. Mean total direct health care costs were EUR 4949 [95% confidence interval (95% CI) EUR 4088–5863, median EUR 2062] per patient over three months. Medication costs represented the largest direct cost category (54% of total direct costs, mean EUR 2658), with mechanistic target of rapamycin (mTOR) inhibitors representing the largest share (47%, EUR 2309). The cost of anti-seizure drugs (ASDs) accounted for a mean of only EUR 260 (5%). Inpatient costs (21%, EUR 1027) and ancillary therapy costs (8%, EUR 407) were also important direct cost components. The mean nursing care-level costs were EUR 1163 (95% CI EUR 1027–1314, median EUR 1635) over three months. Total indirect costs totaled a mean of EUR 2813 (95% CI EUR 2221–3394, median EUR 215) for mothers and EUR 372 (95% CI EUR 193–586, median EUR 0) for fathers. Multiple regression analyses revealed polytherapy with two or more ASDs and the use of mTOR inhibitors as independent cost-driving factors of total direct costs. Disability and psychiatric disease were independent cost-driving factors for total indirect costs as well as for nursing care-level costs. Conclusions: This study revealed substantial direct (including medication), nursing care-level, and indirect costs associated with TSC over three months, highlighting the spectrum of organ manifestations and their treatment needs in the German healthcare setting.
Background Osseointegration is crucial for the long-term success of dental implants and depends on the tissue reaction at the tissue-implant interface. Mechanical properties and biocompatibility make zirconia a suitable material for dental implants, although surface processings are still problematic. The aim of the present study was to compare osteoblast behavior on structured zirconia and titanium surfaces under standardized conditions. Methods The surface characteristics were determined by scanning electron microscopy (SEM). In primary bovine osteoblasts attachment kinetics, proliferation rate and synthesis of bone-associated proteins were tested on different surfaces. Results The results demonstrated that the proliferation rate of cells was significantly higher on zirconia surfaces than on titanium surfaces (p < 0.05; Student's t-test). In contrast, attachment and adhesion strength of the primary cells was significant higher on titanium surfaces (p < 0.05; U test). No significant differences were found in the synthesis of bone-specific proteins. Ultrastructural analysis revealed phenotypic features of osteoblast-like cells on both zirconia and titanium surfaces. Conclusion The study demonstrates distinct effects of the surface composition on osteoblasts in culture. Zirconia improves cell proliferation significantly during the first days of culture, but it does not improve attachment and adhesion strength. Both materials do not differ with respect to protein synthesis or ultrastructural appearance of osteoblasts. Zirconium oxide may therefore be a suitable material for dental implants.
Background The successful use of zirconia ceramics in orthopedic surgery led to a demand for dental zirconium-based implant systems. Because of its excellent biomechanical characteristics, biocompatibility, and bright tooth-like color, zirconia (zirconium dioxide, ZrO2) has the potential to become a substitute for titanium as dental implant material. The present study aimed at investigating the osseointegration of zirconia implants with modified ablative surface at an ultrastructural level. Methods A total of 24 zirconia implants with modified ablative surfaces and 24 titanium implants all of similar shape and surface structure were inserted into the tibia of 12 Gottinger minipigs. Block biopsies were harvested 1 week, 4 weeks or 12 weeks (four animals each) after surgery. Scanning electron microscopy (SEM) analysis was performed at the bone implant interface. Results Remarkable bone attachment was already seen after 1 week which increased further to intimate bone contact after 4 weeks, observed on both zirconia and titanium implant surfaces. After 12 weeks, osseointegration without interposition of an interfacial layer was detected. At the ultrastructural level, there was no obvious difference between the osseointegration of zirconia implants with modified ablative surfaces and titanium implants with a similar surface topography. Conclusion The results of this study indicate similar osseointegration of zirconia and titanium implants at the ultrastructural level.
Sphingosine-1-phosphate (S1P) lyase irreversibly cleaves S1P, thereby catalysing the ultimate step of sphingolipid degradation. We show here that embryonic fibroblasts from S1P lyase-deficient mice (Sgpl1−/−-MEFs), in which S1P and sphingosine accumulate, have features of Niemann-Pick disease type C (NPC) cells. In the presence of serum, overall cholesterol content was elevated in Sgpl1−/−-MEFs, due to upregulation of the LDL receptor and enhanced cholesterol uptake. Despite this, activation of sterol regulatory element-binding protein-2 was increased in Sgpl1−/−-MEFs, indicating a local lack of cholesterol at the ER. Indeed, free cholesterol was retained in NPC1-containing vesicles, which is a hallmark of NPC. Furthermore, upregulation of amyloid precursor protein in Sgpl1−/−-MEFs was mimicked by an NPC1 inhibitor in Sgpl1+/+-MEFs and reduced by overexpression of NPC1. Lysosomal pH was not altered by S1P lyase deficiency, similar to NPC. Interestingly, lysosomal Ca2+ content and bafilomycin A1-induced [Ca2+]i increases were enhanced in Sgpl1−/−-MEFs, contrary to NPC. These results show that both a primary defect in cholesterol trafficking and S1P lyase deficiency cause overlapping phenotypic alterations, and challenge the present view on the role of sphingosine in lysosomal Ca2+ homeostasis.
Schriftenschau
(2011)
Introduction: Clinically complex patients often require multiple medications. Polypharmacy is associated with inappropriate prescriptions, which may lead to negative outcomes. Few effective tools are available to help physicians optimise patient medication. This study assesses whether an electronic medication management support system (eMMa) reduces hospitalisation and mortality and improves prescription quality/safety in patients with polypharmacy. Methods and analysis: Planned design: pragmatic, parallel cluster-randomised controlled trial; general practices as randomisation unit; patients as analysis unit. As practice recruitment was poor, we included additional data to our primary endpoint analysis for practices and quarters from October 2017 to March 2021. Since randomisation was performed in waves, final study design corresponds to a stepped-wedge design with open cohort and step-length of one quarter. Scope: general practices, Westphalia-Lippe (Germany), caring for BARMER health fund-covered patients. Population: patients (≥18 years) with polypharmacy (≥5 prescriptions). Sample size: initially, 32 patients from each of 539 practices were required for each study arm (17 200 patients/arm), but only 688 practices were randomised after 2 years of recruitment. Design change ensures that 80% power is nonetheless achieved. Intervention: complex intervention eMMa. Follow-up: at least five quarters/cluster (practice). recruitment: practices recruited/randomised at different times; after follow-up, control group practices may access eMMa. Outcomes: primary endpoint is all-cause mortality and hospitalisation; secondary endpoints are number of potentially inappropriate medications, cause-specific hospitalisation preceded by high-risk prescribing and medication underuse. Statistical analysis: primary and secondary outcomes are measured quarterly at patient level. A generalised linear mixed-effect model and repeated patient measurements are used to consider patient clusters within practices. Time and intervention group are considered fixed factors; variation between practices and patients is fitted as random effects. Intention-to-treat principle is used to analyse primary and key secondary endpoints.
Introduction: In the time of increasing resistance and paucity of new drug development there is a growing need for strategies to enhance rational use of antibiotics in German and Austrian hospitals. An evidence-based guideline on recommendations for implementation of antibiotic stewardship (ABS) programmes was developed by the German Society for Infectious Diseases in association with the following societies, associations and institutions: German Society of Hospital Pharmacists, German Society for Hygiene and Microbiology, Paul Ehrlich Society for Chemotherapy, The Austrian Association of Hospital Pharmacists, Austrian Society for Infectious Diseases and Tropical Medicine, Austrian Society for Antimicrobial Chemotherapy, Robert Koch Institute.
Materials and methods: A structured literature research was performed in the databases EMBASE, BIOSIS, MEDLINE and The Cochrane Library from January 2006 to November 2010 with an update to April 2012 (MEDLINE and The Cochrane Library). The grading of recommendations in relation to their evidence is according to the AWMF Guidance Manual and Rules for Guideline Development.
Conclusion: The guideline provides the grounds for rational use of antibiotics in hospital to counteract antimicrobial resistance and to improve the quality of care of patients with infections by maximising clinical outcomes while minimising toxicity. Requirements for a successful implementation of ABS programmes as well as core and supplemental ABS strategies are outlined. The German version of the guideline was published by the German Association of the Scientific Medical Societies (AWMF) in December 2013.
Double-differential cross sections have been measured for high-energy p, d, t, 3He, and 4He particles emitted from uranium targets irradiated with 20Ne ions at energies of 250, 400, and 2100 MeV/nucleon and 4He ions at 400 MeV/nucleon. By using the shape and yield of the proton energy spectra, the shape and yield of the d, t, 3He, and 4He energy spectra can be deduced at all measured angles for all incident projectile energies by assuming that they are formed by a coalescence of cascade nucleons, using a model analogous to that of Butler and Pearson, and Schwarzschild and Zupancic-caron.