Intensity modulated radiotherapy for high risk prostate cancer based on sentinel node SPECT imaging for target volume definition

BACKGROUND: The RTOG 94-13 trial has provided evidence that patients with high risk prostate cancer benefit from an additional radiotherapy to the pelvic nodes combined with concomitant hormonal ablation. Since lymphatic drainage of the prostate is highly variable, the optimal target volume definition for the pelvic lymph nodes is problematic. To overcome this limitation, we tested the feasibility of an intensity modulated radiation therapy (IMRT) protocol, taking under consideration the individual pelvic sentinel node drainage pattern by SPECT functional imaging. METHODS: Patients with high risk prostate cancer were included. Sentinel nodes (SN) were localised 1.5–3 hours after injection of 250 MBq (99m)Tc-Nanocoll using a double-headed gamma camera with an integrated X-Ray device. All sentinel node localisations were included into the pelvic clinical target volume (CTV). Dose prescriptions were 50.4 Gy (5 × 1.8 Gy / week) to the pelvis and 70.0 Gy (5 × 2.0 Gy / week) to the prostate including the base of seminal vesicles or whole seminal vesicles. Patients were treated with IMRT. Furthermore a theoretical comparison between IMRT and a three-dimensional conformal technique was performed. RESULTS: Since 08/2003 6 patients were treated with this protocol. All patients had detectable sentinel lymph nodes (total 29). 4 of 6 patients showed sentinel node localisations (total 10), that would not have been treated adequately with CT-based planning ('geographical miss') only. The most common localisation for a probable geographical miss was the perirectal area. The comparison between dose-volume-histograms of IMRT- and conventional CT-planning demonstrated clear superiority of IMRT when all sentinel lymph nodes were included. IMRT allowed a significantly better sparing of normal tissue and reduced volumes of small bowel, large bowel and rectum irradiated with critical doses. No gastrointestinal or genitourinary acute toxicity Grade 3 or 4 (RTOG) occurred. CONCLUSION: IMRT based on sentinel lymph node identification is feasible and reduces the probability of a geographical miss. Furthermore, IMRT allows a pronounced sparing of normal tissue irradiation. Thus, the chosen approach will help to increase the curative potential of radiotherapy in high risk prostate cancer patients

Multiparticle azimuthal correlations for extracting event-by-event elliptic and triangular flow in Au + Au collisions at sNN =200 GeV

We present measurements of elliptic and triangular azimuthal anisotropy of charged particles detected at forward rapidity 1<|η|<3 in Au + Au collisions at sNN=200 GeV, as a function of centrality. The multiparticle cumulant technique is used to obtain the elliptic flow coefficients v2{2},v2{4},v2{6}, and v2{8}, and triangular flow coefficients v3{2} and v3{4}. Using the small-variance limit, we estimate the mean and variance of the event-by-event v2 distribution from v2{2} and v2{4}. In a complementary analysis, we also use a folding procedure to study the distributions of v2 and v3 directly, extracting both the mean and variance. Implications for initial geometrical fluctuations and their translation into the final-state momentum distributions are discussed

Nonperturbative transverse-momentum-dependent effects in dihadron and direct photon-hadron angular correlations in p+p collisions at s =200 GeV

Dihadron and isolated direct photon-hadron angular correlations are measured in p+p collisions at s=200 GeV. The correlations are sensitive to nonperturbative initial-state and final-state transverse momenta kT and jT in the azimuthal nearly back-to-back region Δφ∼π. To have sensitivity to small transverse momentum scales, nonperturbative momentum widths of pout, the out-of-plane transverse-momentum component perpendicular to the trigger particle, are measured. In this region, the evolution of pout can be studied when several different hard scales are measured. These widths are used to investigate possible effects from transverse-momentum-dependent factorization breaking. When accounting for the longitudinal-momentum fraction of the away-side hadron with respect to the near-side trigger particle, the widths are found to increase with the hard scale; this is qualitatively similar to the observed behavior in Drell-Yan and semi-inclusive deep-inelastic scattering interactions, where factorization is predicted to hold. The momentum widths are also studied as a function of center-of-mass energy by comparing to previous measurements at s=510 GeV. The nonperturbative jet widths also appear to increase with s at a similar xT, which is qualitatively consistent to similar measurements in Drell-Yan interactions. Future detailed global comparisons between measurements of processes where transverse-momentum-dependent factorization is predicted to hold and be broken will provide further insight into the role of color in hadronic interactions

Nonperturbative-transverse-momentum broadening in dihadron angular correlations in sNN =200 GeV proton-nucleus collisions

The PHENIX collaboration has measured high-pT dihadron correlations in p+p, p+Al, and p+Au collisions at sNN=200 GeV. The correlations arise from inter- and intrajet correlations and thus have sensitivity to nonperturbative effects in both the initial and final states. The distributions of pout, the transverse-momentum component of the associated hadron perpendicular to the trigger hadron, are sensitive to initial- and final-state transverse momenta. These distributions are measured multidifferentially as a function of xE, the longitudinal momentum fraction of the associated hadron with respect to the trigger hadron. The near-side pout widths, sensitive to fragmentation transverse momentum, show no significant broadening between p+Au, p+Al, and p+p. The away-side nonperturbative pout widths are found to be broadened in p+Au when compared to p+p; however, there is no significant broadening in p+Al compared to p+p collisions. The data also suggest that the away-side pout broadening is a function of Ncoll, the number of binary nucleon-nucleon collisions, in the interaction. The potential implications of these results with regard to initial- and final-state transverse-momentum broadening and energy loss of partons in a nucleus, among other nuclear effects, are discussed

Pseudorapidity Dependence of Particle Production and Elliptic Flow in Asymmetric Nuclear Collisions of p+Al, p+Au, d+Au, and ^{3}He+Au at sqrt[s_{NN}]=200 GeV.

Asymmetric nuclear collisions of p+Al, p+Au, d+Au, and ^{3}He+Au at sqrt[s_{NN}]=200  GeV provide an excellent laboratory for understanding particle production, as well as exploring interactions among these particles after their initial creation in the collision. We present measurements of charged hadron production dN_{ch}/dη in all such collision systems over a broad pseudorapidity range and as a function of collision multiplicity. A simple wounded quark model is remarkably successful at describing the full data set. We also measure the elliptic flow v_{2} over a similarly broad pseudorapidity range. These measurements provide key constraints on models of particle emission and their translation into flow

Measurements of μμ pairs from open heavy flavor and Drell-Yan in p+p collisions at s =200 GeV

PHENIX reports differential cross sections of μμ pairs from semileptonic heavy-flavor decays and the Drell-Yan production mechanism measured in p+p collisions at s=200 GeV at forward and backward rapidity (1.2<|η|<2.2). The μμ pairs from cc, bb, and Drell-Yan are separated using a template fit to unlike- and like-sign muon pair spectra in mass and pT. The azimuthal opening angle correlation between the muons from cc and bb decays and the pair-pT distributions are compared to distributions generated using pythia and powheg models, which both include next-to-leading order processes. The measured distributions for pairs from cc are consistent with pythia calculations. The cc data present narrower azimuthal correlations and softer pT distributions compared to distributions generated from powheg. The bb data are well described by both models. The extrapolated total cross section for bottom production is 3.75±0.24(stat)±0.500.35(syst)±0.45(global) [μb], which is consistent with previous measurements at the Relativistic Heavy Ion Collider in the same system at the same collision energy and is approximately a factor of 2 higher than the central value calculated with theoretical models. The measured Drell-Yan cross section is in good agreement with next-to-leading-order quantum-chromodynamics calculations

Measurement of charm and bottom production from semileptonic hadron decays in p+p collisions at s =200 GeV

Measurements of the differential production of electrons from open-heavy-flavor hadrons with charm- and bottom-quark content in p+p collisions at s=200 GeV are presented. The measurements proceed through displaced-vertex analyses of electron tracks from the semileptonic decay of charm and bottom hadrons using the PHENIX silicon-vertex detector. The relative contribution of electrons from bottom decays to inclusive heavy-flavor-electron production is found to be consistent with fixed-order-plus-next-to-leading-log perturbative-QCD calculations within experimental and theoretical uncertainties. These new measurements in p+p collisions provide a precision baseline for comparable forthcoming measurements in A+A collisions

Earthquake source parameters and scaling relationships in Hungary (central Pannonian basin)

Abstract Fifty earthquakes that occurred in Hungary (central part of the Pannonian basin) with local magnitude ML ranging from 0.8 to 4.5 have been analyzed. The digital seismograms used in this study were recorded by six permanent broad-band stations and twenty short-period ones at hypocentral distances between 10 and 327 km. The displacement spectra for P- and SH-waves were analyzed according to Brune’s source model. Observed spectra were corrected for path-dependent attenuation effects using an independent regional estimate of the quality factor QS. To correct spectra for near-surface attenuation, the k parameterwas calculated, obtaining it fromwaveforms recorded at short epicentral distances. The values of the k parameter vary between 0.01 to 0.06 s with a mean of 0.03 s for P-waves and between 0.01 to 0.09 s with a mean of 0.04 s for SH-waves. After correction for attenuation effects, spectral parameters (corner frequency and low-frequency spectral level) were estimated by a grid search algorithm. The obtained seismic moments range from4.21×1011 to 3.41×1015 Nm (1.7≤Mw ≤4.3). The source radii are between 125 and 1343 m. Stress drop values vary between 0.14 and 32.4 bars with a logarithmic mean of 2.59 bars (1 bar = 105 Pa). From the results, a linear relationship between local andmomentmagnitudes has been established. The obtained scaling relations show slight evidence of self-similarity violation. However, due to the high scatter of our data, the existence of self-similarity cannot be excluded

RNAi screening identifies Trypanosoma brucei stress response protein kinases required for survival in the mouse

Protein kinases (PKs) are a class of druggable targets in Trypanosoma brucei, the causative agent of Human African Trypanosomiasis (sleeping sickness), yet little is known about which PKs are essential for survival in mammals. A recent kinome-wide RNAi screen with 176 individual bloodstream form Trypanosoma brucei lines identified PKs required for proliferation in culture. In order to assess which PKs are also potential virulence factors essential in vivo, lines were pooled, inoculated into mice, and screened for loss of fitness after 48 h RNAi. The presence of trypanosomes in the bloodstream was assessed using RNAi target sequencing (RITseq) and compared to growth in culture. We identified 49 PKs with a significant loss of fitness in vivo in two independent experiments, and a strong correlation between in vitro and in vivo loss of fitness for the majority. Nine PKs had a more pronounced growth defect in vivo, than in vitro. Amongst these PKs were several with putative functions related to stress responses mediated through the PI3K/TOR or MAPK signaling cascades, which act to protect the parasite from complement-mediated and osmotic lysis. Identification of these virulence-associated PKs provides new insights into T. brucei-host interaction and reveals novel potential protein kinase drug targets