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Simple Summary: Renal insufficiency is frequently seen in newly diagnosed multiple myeloma and can be due to the disease itself but also caused by medical interventions or infections. Patients with severe renal insufficiency are known to have an adverse prognosis, but recently, it was shown that even moderately impaired kidney function can have long-term sequelae. Achieving quick disease control by effective antimyeloma therapy can lead to the recovery of renal function. We investigated the kidney-specific variables in a large cohort of 770 myeloma patients receiving three different three-drug regimens for initial myeloma treatment to learn more about the differential effects on kidney function in an early disease phase. All regimens had a positive impact on kidney function without a difference in the proportion of patients who reached normal renal function after three cycles. Interestingly, patients who received bortezomib, lenalidomide, and dexamethasone tended to have higher risk for a worse renal function following induction when compared to the initial values.
Abstract: Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex; VCD) or btz, lenalidomide (len), and dex (VRd) or len, adriamycin, and dex (RAD). The minimum required estimated glomerular filtration rate (eGFR) was >30 mL/min. We analyzed the percent change of the renal function using the International Myeloma Working Group (IMWG) criteria and Kidney Disease: Improving Global Outcomes (KDIGO)-defined categories. Results: Seven hundred and seventy-two patients were eligible. Three hundred and fifty-six received VCD, 214 VRd, and 202 RAD. VCD patients had the best baseline eGFR. The proportion of pts with eGFR <45 mL/min decreased from 7.3% at baseline to 1.9% PInd (p < 0.0001). Thirty-seven point one percent of VCD versus 49% of VRd patients had a decrease of GFR (p = 0.0872). IMWG-defined “renal complete response (CRrenal)” was achieved in 17/25 (68%) pts after VCD, 12/19 (63%) after RAD, and 14/27 (52%) after VRd (p = 0.4747). Conclusions: Analyzing a large and representative newly diagnosed myeloma (NDMM) group, we found no difference in CRrenal that occurred independently from the myeloma response across the three regimens. A trend towards deterioration of the renal function with VRd versus VCD may be explained by a better pretreatment “renal fitness” in the latter group.
Simulation results for future measurements of electromagnetic proton form factors at PANDA (FAIR) within the PandaRoot software framework are reported. The statistical precision with which the proton form factors can be determined is estimated. The signal channel p¯p→e+e− is studied on the basis of two different but consistent procedures. The suppression of the main background channel, i.e. p¯p→π+π−, is studied. Furthermore, the background versus signal efficiency, statistical and systematical uncertainties on the extracted proton form factors are evaluated using two different procedures. The results are consistent with those of a previous simulation study using an older, simplified framework. However, a slightly better precision is achieved in the PandaRoot study in a large range of momentum transfer, assuming the nominal beam conditions and detector performance.
This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, |GE | and |GM|, using the ¯pp → μ+μ− reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is ¯pp → π+π−,due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distribuations of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.
Activation of hypoxia inducible factor 1 is a general phenomenon in infections with human pathogens
(2010)
Background: Hypoxia inducible factor (HIF)-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases. Methodology/Principal Findings: Using patient skin biopsies, cell culture and murine infection models, HIF-1 activation was determined by immunohistochemistry, immunoblotting and reporter gene assays and was linked to cellular oxygen consumption. The course of a S. aureus peritonitis was determined upon pharmacological HIF-1 inhibition. Activation of HIF-1 was detectable (i) in all ex vivo in biopsies of patients suffering from skin infections, (ii) in vitro using cell culture infection models and (iii) in vivo using murine intravenous and peritoneal S. aureus infection models. HIF-1 activation by human pathogens was induced by oxygen-dependent mechanisms. Small colony variants (SCVs) of S. aureus known to cause chronic infections did not result in cellular hypoxia nor in HIF-1 activation. Pharmaceutical inhibition of HIF-1 activation resulted in increased survival rates of mice suffering from a S. aureus peritonitis. Conclusions/Significance: Activation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections.
The quark gluon plasma produced in heavy ion collisions behaves like an almost ideal fluid described by viscous hydrodynamics with a number of transport coefficients. The second order coefficient κ is related to a Euclidean correlator of the energy-momentum tensor at vanishing frequency and low momentum. This allows for a lattice determination without maximum entropy methods or modelling, but the required lattice sizes represent a formidable challenge. We calculate κ in leading order lattice perturbation theory and simulations on 1203 × 6, 8 lattices with a < 0.1 fm. In the temperature range 2Tc − 10Tc we find κ = 0.36(15)T2. The error covers both a suitably rescaled AdS/CFT prediction as well as, remarkably, the result of leading order perturbation theory. This suggests that appropriate noise reduction methods on the lattice and NLO perturbative calculations could provide an accurate QCD prediction in the near future.
LatticeQCD using OpenCL
(2011)
Das Schwerionenkollisionen Programm der Beschleuniger RHIC und LHC gibt Hinweise auf einen neuen Zustand hadronischer Materie --- das Quark-Gluon Plasma. Dieses zeichnet sich durch eine zumindest partielle Aufhebung des confinements aus, welches besagt, dass keine freien Quarks beochtbar sind.
Aus einer Beschreibung der experimentellen Daten mit relativistischer Hydrodynamik folgen weitere Eigenschaften. So geht das in einer Schwerionenkollision erzeugte Quark-Gluon Plasma nach sehr kurzer Zeit, etwa 1 fm/c, in ein zumindest lokales thermisches Gleichgewicht über. Durch die Lorentzkontraktion der beiden Schwerionen erwartet man, dass der Zustand direkt nach der Kollision durch eine Impulsanisotropie in der transversal-longitudinalen Ebene bestimmt wird. Somit setzt das Erreichen eines thermischen Gleichgewichts zunächst eine Isotropisierung voraus. Bisherige Studien haben gezeigt, dass gluonische Moden bei dieser Isotropisierung durch Verursachung einer chromo-Weibel Instabilität eine entscheidende Rolle spielen.
Weiterhin verhält sich das Quark-Gluon Plasma wie eine fast perfekte Flüssigkeit. Eine Berücksichtigung dissipativer Terme in der hydrodynamischen Beschreibung erfordert das Hinzufügen weiterer Terme zu den entsprechenden Bewegungsgleichungen. Diese sind proportional zu Transportkoeffizienten, welche durch die zugrunde liegende mikroskopische Theorie festgelegt sind.
Diese Theorie ist Quantenchromodynamik. Sie beschreibt die starke Wechselwirkung der Quarks und Gluonen und ist ein fundamentaler Baustein des Standardmodells der Teilchenphysik. Da im Regelfall Prozesse der starken Wechselwirkung nichtperturbativ sind, beschreiben wir QCD unter Verwendung einer Gitterregularisierung. Diese beruht auf einer Diskretisierung der vierdimensionalen Euklidischen Raumzeit durch einen Hyperkubus mit periodischen Randbedingungen und ermöglicht ein Lösen der QCD mit numerischen Methoden. Allerdings ist die Anwendung der Gittereichtheorie auf Systeme im thermischen Gleichgewicht beschränkt und kann somit keine Prozesse beschreiben, die auf Echtzeit basieren.
Transportkoeffizienten entsprechen Proportionalitätskoeffizienten, die die Relaxation einer Flüssigkeit oder eben eines Quark-Gluon Plasmas von einer kleinen Störung beschreiben. Damit sind sie unmittelbar mit der Zeit verknüpft. Über Kubo-Formeln lassen sie sich jedoch mit Gleichgewichtserwartungswerten retardierter Korrelatoren verknüpfen und werden so in Gitter QCD zugänglich.
In der vorliegenden Dissertation berechnen wir den Transportkoeffizienten κ in Gittereichtheorie für das Yang-Mills Plasma. Dabei nutzen wir aus, dass dieser Transportkoeffizient eine triviale analytische Fortsetzung vom retardierten zum Euklidischen Korrelator besitzt, welcher direkt in Gittereichtheorie zugänglich ist. Es ist die erste nichtperturbative Berechnung eines Transportkoeffizienten in QCD ohne weitere Annahmen, wie die Maximum Entropie Methode oder Ansätze, zu treffen.
Two-particle correlation functions of negative hadrons over wide phase space, and transverse mass spectra of negative hadrons and deuterons near mid-rapidity have been measured in central Pb+Pb collisions at 158 GeV per nucleon by the NA49 experiment at the CERN SPS. A novel Coulomb correction procedure for the negative two-particle correlations is employed making use of the measured oppositely charged particle correlation. Within an expanding source scenario these results are used to extract the dynamic characteristics of the hadronic source, resolving the ambiguities between the temperature and transverse expansion velocity of the source, that are unavoidable when single and two particle spectra are analysed separately. The source shape, the total duration of the source expansion, the duration of particle emission, the freeze-out temperature and the longitudinal and transverse expansion velocities are deduced.
We report measurements of Xi and Xi-bar hyperon absolute yields as a function of rapidity in 158 GeV/c Pb+Pb collisions. At midrapidity, dN/dy = 2.29 +/- 0.12 for Xi, and 0.52 +/- 0.05 for Xi-bar, leading to the ratio of Xi-bar/Xi = 0.23 +/- 0.03. Inverse slope parameters fitted to the measured transverse mass spectra are of the order of 300 MeV near mid-rapidity. The estimated total yield of Xi particles in Pb+Pb central interactions amounts to 7.4 +/- 1.0 per collision. Comparison to Xi production in properly scaled p+p reactions at the same energy reveals a dramatic enhancement (about one order of magnitude) of Xi production in Pb+Pb central collisions over elementary hadron interactions.
The directed and elliptic flow of protons and charged pions has been observed from the semi-central collisions of a 158 GeV/nucleon Pb beam with a Pb target. The rapidity and transverse momentum dependence of the flow has been measured. The directed flow of the pions is opposite to that of the protons but both exhibit negative flow at low pt. The elliptic flow of both is fairly independent of rapidity but rises with pt. PACS numbers: 25.75.-q, 25.75.Ld
