To determine the toxicity, maximum-tolerated dose (MTD), and pharmacokinetics of recombinant human CD40 ligand (rhuCD40L) (Avrend; Immunex Corp, Seattle, WA), suggested in preclinical studies to ...mediate cytotoxicity against CD40-expressing tumors and immune stimulation.
Patients with advanced solid tumors or intermediate- or high-grade non-Hodgkin's lymphoma (NHL) received rhuCD40L subcutaneously daily for 5 days in a phase I dose-escalation study. Subsequent courses were given until disease progression.
Thirty-two patients received rhuCD40L at three dose levels. A total of 65 courses were administered. The MTD was 0.1 mg/kg/d based on dose-related but transient elevations of serum liver transaminases. Grade 3 or 4 transaminase elevations occurred in 14%, 28%, and 57% of patients treated at 0.05, 0.10, and 0.15 mg/kg/d, respectively. Other toxicities were mild to moderate. At the MTD, the half-life of rhuCD40L was calculated at 24.8 +/- 22.8 hours. Two patients (6%) had a partial response on study (one patient with laryngeal carcinoma and one with NHL). For the patient with laryngeal cancer, a partial response was sustained for 12 months before the patient was taken off therapy and observed on no additional therapy. Three months later, the patient was found to have a complete response and remains biopsy-proven free of disease at 24 months. Twelve patients (38%) had stable disease after one course, which was sustained in four patients through four courses.
The MTD of rhuCD40L when administered subcutaneously daily for 5 days was defined by transient serum elevations in hepatic transaminases. Encouraging antitumor activity, including a long-term complete remission, was observed. Phase II studies are warranted.
In relativistic heavy-ion collisions, anisotropic collective flow is driven, event by event, by the initial eccentricity of the matter created in the nuclear overlap zone. Interpretation of the ...anisotropic flow data thus requires a detailed understanding of the effective initial source eccentricity of the event sample. In this paper, we investigate various ways of defining this effective eccentricity using the Monte Carlo Glauber (MCG) approach. In particular, we examine the participant eccentricity, which quantifies the eccentricity of the initial source shape by the major axes of the ellipse formed by the interaction points of the participating nucleons. We show that reasonable variation of the density parameters in the Glauber calculation, as well as variations in how matter production is modeled, do not significantly modify the already established behavior of the participant eccentricity as a function of collision centrality. Focusing on event-by-event fluctuations and correlations of the distributions of participating nucleons, we demonstrate that, depending on the achieved event-plane resolution, fluctuations in the elliptic flow magnitude v{sub 2} lead to most measurements being sensitive to the root-mean-square rather than the mean of the v{sub 2} distribution. Neglecting correlations among participants, we derive analytical expressions for the participant eccentricity cumulants as a function of the number of participating nucleons, N{sub part}, keeping nonnegligible contributions up to O(1/N{sub part}{sup 3}). We find that the derived expressions yield the same results as obtained from mixed-event MCG calculations which remove the correlations stemming from the nuclear collision process. Most importantly, we conclude from the comparison with MCG calculations that the fourth-order participant eccentricity cumulant does not approach the spatial anisotropy obtained assuming a smooth nuclear matter distribution. In particular, for the Cu+Cu system, these quantities deviate from each other by almost a factor of 2 over a wide range in centrality. This deviation reflects the essential role of participant spatial correlations in the interaction of two nuclei.
Spectator fragments resulting from relativistic heavy ion collisions, consisting of single protons and neutrons along with groups of stable nuclear fragments up to nitrogen (Z = 7), are measured in ...PHOBOS. These fragments are observed in Au+Au ( sNN=19.6 GeV) and Cu+Cu (22.4 GeV) collisions at high pseudorapidity (η). The dominant multiply-charged fragment is the tightly bound helium (α), with lithium, beryllium, and boron all clearly seen as a function of collision centrality and pseudorapidity. In this paper, we observe that in Cu+Cu collisions, it becomes much more favorable for the α fragments to be released than lithium. The yields of fragments approximately scale with the number of spectator nucleons, independent of the colliding ion. The shapes of the pseudorapidity distributions of fragments indicate that the average deflection of the fragments away from the beam direction increases for more central collisions. Finally, a detailed comparison of the shapes for α and lithium fragments indicates that the centrality dependence of the deflections favors a scaling with the number of participants in the collision.
This Letter presents measurements of the elliptic flow of charged particles as a function of pseudorapidity and centrality from Cu-Cu collisions at 62.4 and 200 GeV using the PHOBOS detector at the ...Relativistic Heavy Ion Collider. The elliptic flow in Cu-Cu collisions is found to be significant even for the most central events. For comparison with the Au-Au results, it is found that the detailed way in which the collision geometry (eccentricity) is estimated is of critical importance when scaling out system-size effects. A new form of eccentricity, called the participant eccentricity, is introduced which yields a scaled elliptic flow in the Cu-Cu system that has the same relative magnitude and qualitative features as that in the Au-Au system.
We present measurements of the pseudorapidity distribution of primary charged particles produced in Au+Au collisions at three energies, sqrts(NN)=19.6, 130, and 200 GeV, for a range of collision ...centrali-ties. The distribution narrows for more central collisions and excess particles are produced at high pseudorapidity in peripheral collisions. For a given centrality, however, the distributions are found to scale with energy according to the "limiting fragmentation" hypothesis. The universal fragmentation region described by this scaling grows in pseudorapidity with increasing collision energy, extending well away from the beam rapidity and covering more than half of the pseudorapidity range over which particles are produced. This approach to a universal limiting curve appears to be a dominant feature of the pseudorapidity distribution and therefore of the total particle production in these collisions.
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