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There is little doubt that Quantumchromodynamics (QCD) is the theory which describes strong interaction physics. Lattice gauge simulations of QCD predict that in the m,T plane there is a line where a transition from confined hadronic matter to deconfined quarks takes place. The transition is either a cross over (at low m) or of first order (at high m). It is the goal of the present and future heavy ion experiment at RHIC and FAIR to study this phase transition at different locations in the m,T plane and to explore the properties of the deconfined phase. It is the purpose of this contribution to discuss some of the observables which are considered as useful for this purpose.
Die letzte Geschichte des Erzählbands "Die Stadt Ys" trägt nicht nur dessen Titel. Von einigen Unterschieden abgesehen, beginnt sie ebenfalls mit dem Text, der dem Prosaband als Prolog vorhergeht. Er knüpft an die bretonische Sage von der Stadt Ys-Ker an, die das Motiv der versunkenen Stadt variiert.
Die Sage erzählt von einer an der Bucht von Douarnenez in der Normandie gelegenen Stadt Ker-Ys. Sie war einst zu großem Reichtum gelangt, wurde aber wegen verbotener Liebe der Königstochter zum Untergang verurteilt und versank in einer Sturmnacht in den Meeresfluten. Bei Sonnenaufgang soll sie seither als mahnendes Beispiel aus dem Meer ragen, und an klaren, windstillen Tagen wollen Fischer ihre Glocken hören können. Der prologartige Text übernimmt zwar das Motiv des Untergangs und des Wiederauftauchens, jedoch mit der surrealistischen Pointe, dass die Stadt, Paradigma des Festgebaut-Statischen, sich auf Wanderschaft begibt. Formale Entsprechung dieser Paradigmen-Verkehrung ist die Namensinversion. Aus Ker-Ys wird im Prolog Ys-Ker. Titelgebend für den Erzählband ist dann die Reduktion dieses Doppelnamens auf dessen erste Hälfte.
Die Geobotanik oder Vegetationskunde mit all ihren Teildisziplinen (u.a. Biogeographie, Pflanzensoziologie, Pflanzenökologie, Biozönologie, Floren- und Vegetationsgeschichte, Paläoökologie) ist eine der wichtigsten ganzheitlichen Zugänge zur Biologie insgesamt und die Forschungsdisziplin, welche die Aufgabe hat, zeitliche und räumliche Muster der Diversität in der Pflanzenwelt zu dokumentieren, zu analysieren, visualisieren und zu interpretieren. Die Biodiversität ist zu einem Schlüsselbegriff der ökologischen wie auch geobotanischen Forschung geworden. Die belebte Welt unseres Planeten ist von unglaublicher Vielfalt. Die Anzahl bekannter Arten an Pflanzen, Tieren und Mikroorganismen wird derzeit auf 1,4 Millionen veranschlagt, 5 bis 15 Millionen Arten werden global geschätzt. Diese Zahl lässt jedoch viele Plünderte oder Tausende von bislang noch nicht oder nur schlecht bestimmten Arten in gewissen Organismengruppen (z. B. Mikroorganismen) unberücksichtigt, welche bislang noch nicht oder nur unzureichend erfasst und beschrieben sind. Die systematische Erfassung aller Arten in international angelegten und intensiv finanzierten Arten erfassungsprogrammen ist eine notwendige Zukunftsaufgabe. Die Einbindung der Pflanzen und Mikroorganismen in die natürlichen Ökosysteme, ihr euryökes oder stenökes Standortverhalten, die Erfassung ihrer Konkurrenzkraft und ihrer Migrationsfähigkeit sind beispielsweise vordergründige Aufgaben. Neben den heute bekannten Arten hat wohl ein Mehrfaches dieser Zahl - vielleicht Millionen oder gar Milliarden - in der Vergangenheit gelebt. Sie sind heute ausgestorben, ohne je einmal lebend beschrieben worden zu sein. Nur ein kleiner Rest ist uns als Fossilien erhalten. Die Biodiversität unserer heutigen Welt muss also verstärkt kausal aus paläoökologischer Sicht beleuchtet werden. Auch die natürliche Variabilität des Klimas, die Geodiversität und die Biodiversität sind als Schätze der heutigen Ökosysteme der Erde zu betrachten. Die Rekonstruktion natürlicher klimatischer Abläufe, die genaue Erfassung der Variabilität und der Schwankungsintensität des natürlichen Klimas und der gegebenenfalls anthropogenen Klimaerwärmung sind vordergründige Aufgaben hochspezialisierter, interdisziplinärer Forschung, an denen die Geobotanik ihren zukommenden Anteil haben wird. Dies wird an einigen Beispielen verdeutlicht. Vor diesem Hintergrund sollen einige Aspekte vordergründiger Probleme des 21. Jahrhunderts aus globaler bis lokaler Perspektive diskutiert und schließlich die Rolle beleuchtet werden, welche geobotanische Forschung zu Beginn dieses neuen Jahrhunderts einnehmen könnte.
Background: SNPs near the interferon lambda (IFNL) 3 gene are predictors for sustained virological response (SVR) in patients with chronic hepatitis C genotype (GT) 1. In addition, a dinucleotide frame shift in ss469415590 was described, which generates IFNL4. In this study, we compared the role of IFNL4 variants with IFNL3-(rs12979860) and IFNL3-(rs8099917) on response to pegylated (PEG)-IFN and Ribavirin (RBV) in patients with chronic hepatitis C GT2/3.
Methods: We recruited 1006 patients with chronic hepatitis C and GT2/3 in a large German registry. A treatment with PEG-IFN and Ribavirin was started by 959 patients. We performed genotyping of IFNL3 (rs12979860, n = 726; rs8099917, n = 687) and of IFNL4 (ss469415590; n = 631).
Results: Both preferable IFNL3 genotypes were associated with RVR (both p<0.0001) rather than with SVR (rs12979860: p = 0.251; rs8099917: p = 0.447). Only RVR was linked to SVR in univariate and multivariate analyzes (both p<0.001). Concordance of genotyping in patients with available serum samples and EDTA blood samples (n = 259) was more than 96% for both IFNL3 SNPs. IFNL3-(rs12979860) correlated with IFNL4: 99.2% of patients with IFNL3-(rs12979860)-CC were IFNL4-(ss469415590)-TT/TT. IFNL3-(rs12979860)-CT was linked with IFNL4-(ss469415590)-TT/ΔG (98.0%) and IFNL3-(rs12979860)-TT was associated with IFNL4-(ss469415590)-ΔG/ΔG (97.6%).
Conclusion: IFNL3 genotyping from serum was highly efficient and can be used as an alternative if EDTA whole blood is not available. In Caucasian GT2/3 patients genotyping for INFL4-(ss469415590) does not lead to additional information for the decision-making process. Importantly, IFNL3 SNPs were not associated with SVR but with RVR. Even in the era of new direct acting antiviral (DAA) therapies, IFNL3 testing may therefore still be considered for naïve GT2/3 patients to decide if dual Peg-IFN/RBV therapy is an option in resource limited regions.
Evidence based clinical guidelines are implemented to treat patients efficiently that include efficacy, tolerability but also health economic considerations. This is of particular relevance to the new direct acting antiviral agents that have revolutionized treatment of chronic hepatitis C. For hepatitis C genotypes 2/3 interferon free treatment is already available with sofosbuvir plus ribavirin. However, treatment with sofosbuvir-based regimens is 10–20 times more expensive compared to pegylated interferon alfa and ribavirin (PegIFN/RBV). It has to be discussed if PegIFN/RBV is still an option for easy to treat patients. We assessed the treatment of patients with chronic hepatitis C genotypes 2/3 with PegIFN/RBV in a real world setting according to the latest German guidelines. Overall, 1006 patients were recruited into a prospective patient registry with 959 having started treatment. The intention-to-treat analysis showed poor SVR (GT2 61%, GT3 47%) while patients with adherence had excellent SVR in the per protocol analysis (GT2 96%, GT3 90%). According to guidelines, 283 patients were candidates for shorter treatment duration, namely a treatment of 16 weeks (baseline HCV-RNA <800.000 IU/mL, no cirrhosis and RVR). However, 65% of these easy to treat patients have been treated longer than recommended that resulted in higher costs but not higher SVR rates. In conclusion, treatment with PegIFN/RBV in a real world setting can be highly effective yet similar effective than PegIFN± sofosbuvir/RBV in well-selected naïve G2/3 patients. Full adherence to guidelines could be further improved, because it would be important in the new era with DAA, especially to safe resources.
Objective We assessed the effectiveness and safety of daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in a large real-world cohort, including patients with advanced liver disease.
Design Adults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options were treated in a European compassionate use programme. The recommended regimen was DCV 60 mg plus SOF 400 mg for 24 weeks; RBV addition or shorter duration was allowed at physicians' discretion. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12).
Results Of the 485 evaluable patients, 359 received DCV+SOF and 126 DCV+SOF+RBV. Most patients were men (66%), white (93%) and treatment-experienced (70%). The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%), and 80% of patients had cirrhosis (42% Child–Pugh B/C; 46% Model for End-Stage Liver Disease score >10). SVR12 (modified intention-to-treat) was achieved by 91% of patients (419/460); 1 patient had virological breakthrough and 13 patients relapsed. Virological failure was not associated with treatment group (adjusted risk difference DCV+SOF minus DCV+SOF+RBV: 1.06%; 95% CI −2.22% to 4.35%). High SVR12 was observed regardless of HCV genotype or cirrhosis, liver transplant or HIV/HCV coinfection status. Twenty eight patients discontinued treatment due to adverse events (n=18) or death (n=10) and 18 died during follow-up. Deaths and most safety events were associated with advanced liver disease and not considered treatment related.
Conclusions DCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease.
Trial registration number NCT0209966.
We describe two independent frameworks which provide unambiguous determinations of the deconfinement and the decoupling conditions of a relativistic gas at finite temperature. First, we use the Polyakov-Nambu-Jona–Lasinio model to compute meson and baryon masses at finite temperature and determine their melting temperature as a function of their strangeness content. Second, we analyze a simple expanding gas within a Friedmann-Robertson-Walker metric, which admits a well-defined decoupling mechanism. We examine the decoupling time as a function of the particle mass and cross section. We find evidences of an inherent dependence of the hadronization and freeze-out conditions on flavor, and on mass and cross section, respectively.
Der Prosaband "Die Stadt Ys" erschien 2007. Er ist nach den Romanen "Rosa" (2000) und "Heldenfriedhof" (2006) Harlans letzte Prosaveröffentlichung, an deren Herausgabe er selbst mitwirkte und deren Druckfassung er autorisierte. [...] Über die zumeist kleinformatigen Kurzgeschichten ist Harlans perturbatorische Erzählweise eher zugänglich als über die erheblich großformatigeren Geschichten im letzten der drei Teile des Prosabands oder gar über die Iyob-Geschichte im mittleren Teil oder die Romane. Daher hat die Untersuchung der Kurzgeschichten hinsichtlich der folgenden Texte eine propädeutische Funktion. Sie zeigt auf dem Weg eines close reading, mit welchen erzählerischen Mitteln Harlans Text Leser:innen, die kohärente, sukzessiv-linear zu lesende Texte erwarten, extrem verwirren und hilft auf diese Weise vielleicht, diese Verwirrung nicht nur zu tolerieren, sondern den Blick freiwerden zu lassen für die staunenswerte Virtuosität dieser Texte.
Background: Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate treatment responses who may require treatment modification. However, there are only very limited data concerning the real-world clinical management of patients with PBC in Germany. Objective: The aim of this retrospective multicenter study was to evaluate response rates to standard first-line UDCA therapy and subsequent Second-line treatment regimens in a large cohort of well-characterized patients with PBC from 10 independent hepatological referral centers in Germany prior to the introduction of obeticholic acid as a licensed second-line treatment option. Methods: Diagnostic confirmation of PBC, standard first-line UDCA treatment regimens and response rates at 12 months according to Paris-I, Paris-II, and Barcelona criteria, the follow-up cut-off alkaline phosphatase (ALP) ≤ 1.67 × upper limit of normal (ULN) and the normalization of bilirubin (bilirubin ≤ 1 × ULN) were retrospectively examined between June 1986 and March 2017. The management and hitherto applied second-line treatment regimens in patients with an inadequate response to UDCA and subsequent response rates at 12 months were also evaluated. Results: Overall, 480 PBC patients were included in this study. The median UDCA dosage was 13.2 mg UDCA/kg bodyweight (BW)/d. Adequate UDCA treatment response rates according to Paris-I, Paris-II, and Barcelona criteria were observed in 91, 71.3, and 61.3% of patients, respectively. In 83.8% of patients, ALP ≤ 1.67 × ULN were achieved. A total of 116 patients (24.2%) showed an inadequate response to UDCA according to at least one criterion. The diverse second-line treatment regimens applied led to significantly higher response rates according to Paris-II (35 vs. 60%, p = 0.005), Barcelona (13 vs. 34%, p = 0.0005), ALP ≤ 1.67 × ULN and bilirubin ≤ 1 × ULN (52.1 vs. 75%, p = 0.002). The addition of bezafibrates appeared to induce the strongest beneficial effect in this cohort (Paris II: 24 vs. 74%, p = 0.004; Barcelona: 50 vs. 84%, p = 0.046; ALP < 1.67 × ULN and bilirubin ≤ 1 × ULN: 33 vs. 86%, p = 0.001). Conclusion: Our large retrospective multicenter study confirms high response rates following UDCA first-line standard treatment in patients with PBC and highlights the need for close monitoring and early treatment modification in high-risk patients with an insufficient response to UDCA since early treatment modification significantly increases subsequent response rates of these patients.
