Lack of host gut microbiota alters immune responses and intestinal granuloma formation during schistosomiasis.

Fatalities from schistosome infections arise due to granulomatous, immune-mediated responses to eggs that become trapped in host tissues. Schistosome-specific immune responses are characterized by initial T helper type 1 (Th1) responses and our previous studies demonstrated that myeloid differentiation primary response gene 88 (Myd88)-deficient mice failed to initiate such responses in vivo. Paradoxically, schistosomal antigens fail to stimulate innate cells to release proinflammatory cytokines in vitro. Since Schistosoma mansoni infection is an intestinal disease, we hypothesized that commensal bacteria could act as bystander activators of the intestinal innate immune system to instigate Th1 responses. Using a broad spectrum of orally administered antibiotics and anti-mycotics we analysed schistosome-infected mice that were simultaneously depleted of gut bacteria. After depletion there was significantly less inflammation in the intestine, which was accompanied by decreased intestinal granuloma development. In contrast, liver pathology remained unaltered. In addition, schistosome-specific immune responses were skewed and faecal egg excretion was diminished. This study demonstrates that host microbiota can act as a third partner in instigating helminth-specific immune responses.

Antiproton induced DNA damage: proton like in flight, carbon-ion like near rest.

Biological validation of new radiotherapy modalities is essential to understand their therapeutic potential. Antiprotons have been proposed for cancer therapy due to enhanced dose deposition provided by antiproton-nucleon annihilation. We assessed cellular DNA damage and relative biological effectiveness (RBE) of a clinically relevant antiproton beam. Despite a modest LET (~19 keV/µm), antiproton spread out Bragg peak (SOBP) irradiation caused significant residual γ-H2AX foci compared to X-ray, proton and antiproton plateau irradiation. RBE of ~1.48 in the SOBP and ~1 in the plateau were measured and used for a qualitative effective dose curve comparison with proton and carbon-ions. Foci in the antiproton SOBP were larger and more structured compared to X-rays, protons and carbon-ions. This is likely due to overlapping particle tracks near the annihilation vertex, creating spatially correlated DNA lesions. No biological effects were observed at 28-42 mm away from the primary beam suggesting minimal risk from long-range secondary particles.

SU-E-T-610: Impact of Variable Beam Spot Size on Treatment Time in Particle Therapy.

PURPOSE: The dosimetric advantage of particle therapy comes with a much higher infrastructure investment and operation costs. Increasing patient throughput is a key factor to manage operation costs. We investigate the impact of variable beam spot sizes on treatment time and discuss the tradeoffs involved. METHODS: The following realistic assumptions were used. (1) The beam traveling speed is independent of the beam spot size. (2) The beam spot is a 2D Gaussian. Changing the beam spot size implies varying the standard deviation. (3) The maximum beam intensity is a constant independent of the beam spot size. Increasing the beam spot reduces the fluence. (4) Varying the beam spot size incurs in a reset time penalty.A 2D tumor was used in the study. Dose calculations were based on pencil beam kernels from GEANT4.The total treatment time is divided into the beam travel time, the beam-on time, andthe time for changing the spot size. RESULTS: We found that: (1) Changing the beam spot size has no impact on the beam-on time, because the maximum beam intensity is independentof the beam spot and increasing the beam spot only reduces the fluence. (2) Larger beam spot size shortens the total travel time inversely proportional to the radius of the beam spot. (3) Plans with different beam spot sizes have similar dosimetric qualities. (4) If higher beam intensity could be used for larger beam spot size, savings in beam-on time would be inversely proportional to the intensity available. CONCLUSIONS: We have studied the interplay among beam intensity, travel time, and beam size reset time for a scanning beam with variable beam spot size. Our initial studies show necessary conditions for and limitations on savings in total treatment times. Further studies are being carried out to find additional time saving sources. Supported in part by NSF CBET-0853157.

SU-E-T-105: The LET Dependence of Liquid Ionization Chambers (LICs) in High-LET Beams.

PURPOSE: LICs are novel detectors for radiotherapy: the higher density of the medium allows to build them with a smaller sensitive volume, making them appealing in particle therapy. With RBE varying along the depth dose curve (DDC) and with the rising interest in dose/LET-painting, verifying the LET is becoming more important. Nevertheless, while the LET distributions for different ionizing particles have been calculated, they have never been directly measured in realistic therapeutic beams. Our interest in LICs is based on the characterization of the beam quality in terms of LET. It has been shown in earlier works that the extrapolation of the linear portion of the voltage curve yields an intercept with the x-axis that depends on LET. The quantitative establishment of this method, however, depends on how accurately recombination effects are taken into account. METHODS: Due to the higher density of charge carriers produced in the liquid, LICs have high recombination effects: general recombination effects, involving pairs belonging to different tracks (dose rate dependent), and initial recombination between ion-electron pairs belonging to the same incident particle event (LET dependent). To perform this study we propose a two-dimensional array of LICs, composed by a 16×8 matrix of 2×2 mm2 pixels, which gives a fine spatial resolution on the plane. RESULTS: Voltage curves have been measured for proton, carbon and oxygen beams available at the HIT facility in Heidelberg for different energies and dose rates. After correcting the curves for general recombination losses using the Three Voltage Method, we have indications of dose rate independence, indicating successful correction. CONCLUSIONS: Further investigations are foreseen to quantify the LET dependence along the DDC, where different LET values are expected. A comparison with simulated dose averaged LET values will give quantitative information about 2D LET distributions for different beam species.

Indications of proton-dominated cosmic-ray composition above 1.6 EeV.

We report studies of ultrahigh-energy cosmic-ray composition via analysis of depth of air shower maximum (X(max)), for air shower events collected by the High-Resolution Fly's Eye (HiRes) observatory. The HiRes data are consistent with a constant elongation rate d/d[log(E)] of 47.9+/-6.0(stat)+/-3.2(syst) g/cm2/decade for energies between 1.6 and 63 EeV, and are consistent with a predominantly protonic composition of cosmic rays when interpreted via the QGSJET01 and QGSJET-II high-energy hadronic interaction models. These measurements constrain models in which the galactic-to-extragalactic transition is the cause of the energy spectrum ankle at 4x10(18) eV.

Real-time imaging for dose evaluation during antiproton irradiation.

Online monitoring of the stopping distribution of particle beams used for radiotherapy provides the possibility of detecting possible errors in dose deposition early during a given treatment session, and may therefore help to improve the quality of the therapy. Antiproton annihilation events produce several long-range secondary particles which can be detected in real time by standard high energy particle physics detector systems. In this note, Monte Carlo calculations are performed in order to study the feasibility of real-time imaging by detecting charged pions produced during antiproton irradiation of typical biological targets. A simple treatment plan in a water phantom is simulated and the results show that by detecting pi+/- the position and the size of the planned target volume can be located with precision in the order of 1 mm.

First observation of the Greisen-Zatsepin-Kuzmin suppression.

The High Resolution Fly's Eye (HiRes) experiment has observed the Greisen-Zatsepin-Kuzmin suppression (called the GZK cutoff) with a statistical significance of five standard deviations. HiRes' measurement of the flux of ultrahigh energy cosmic rays shows a sharp suppression at an energy of 6 x 10(19) eV, consistent with the expected cutoff energy. We observe the ankle of the cosmic-ray energy spectrum as well, at an energy of 4 x 10(18) eV. We describe the experiment, data collection, and analysis and estimate the systematic uncertainties. The results are presented and the calculation of the statistical significance of our observation is described.

The antiproton depth-dose curve in water.

We have measured the depth-dose curve of 126 MeV antiprotons in a water phantom using ionization chambers. Since the antiproton beam provided by CERN has a pulsed structure and possibly carries a high-LET component from the antiproton annihilation, it is necessary to correct the acquired charge for ion recombination effects. The results are compared with Monte Carlo calculations and were found to be in good agreement. Based on this agreement we calculate the antiproton depth-dose curve for antiprotons and compare it with that for protons and find a doubling of the physical dose in the peak region for antiprotons.

Measurement of the flux of ultrahigh energy cosmic rays from monocular observations by the High Resolution Fly's Eye experiment.

We have measured the cosmic ray spectrum above 10(17.2) eV using the two air-fluorescence detectors of the High Resolution Fly's Eye observatory operating in monocular mode. We describe the detector, phototube, and atmospheric calibrations, as well as the analysis techniques for the two detectors. We fit the spectrum to a model consisting of galactic and extragalactic sources.

Production and detection of cold antihydrogen atoms.

A theoretical underpinning of the standard model of fundamental particles and interactions is CPT invariance, which requires that the laws of physics be invariant under the combined discrete operations of charge conjugation, parity and time reversal. Antimatter, the existence of which was predicted by Dirac, can be used to test the CPT theorem-experimental investigations involving comparisons of particles with antiparticles are numerous. Cold atoms and anti-atoms, such as hydrogen and antihydrogen, could form the basis of a new precise test, as CPT invariance implies that they must have the same spectrum. Observations of antihydrogen in small quantities and at high energies have been reported at the European Organization for Nuclear Research (CERN) and at Fermilab, but these experiments were not suited to precision comparison measurements. Here we demonstrate the production of antihydrogen atoms at very low energy by mixing trapped antiprotons and positrons in a cryogenic environment. The neutral anti-atoms have been detected directly when they escape the trap and annihilate, producing a characteristic signature in an imaging particle detector.