Guided Mode Evolution and Ionization Injection in Meter-Scale Multi-GeV Laser Wakefield Accelerators.

We show that multi-GeV laser wakefield electron accelerators in meter-scale, low density hydrodynamic plasma waveguides operate in a new nonlinear propagation regime dominated by sustained beating of lowest order modes of the ponderomotively modified channel; this occurs whether or not the injected pulse is linearly matched to the guide. For a continuously doped gas jet, this emergent mode beating effect leads to axially modulated enhancement of ionization injection and a multi-GeV energy spectrum of multiple quasimonoenergetic peaks; the same process in a locally doped jet produces single multi-GeV peaks with <10% energy spread. A three-stage model of drive laser pulse evolution and ionization injection characterizes the beating effect and explains our experimental results.

Programmable quantum emitter formation in silicon.

Silicon-based quantum emitters are candidates for large-scale qubit integration due to their single-photon emission properties and potential for spin-photon interfaces with long spin coherence times. Here, we demonstrate local writing and erasing of selected light-emitting defects using femtosecond laser pulses in combination with hydrogen-based defect activation and passivation at a single center level. By choosing forming gas (N2/H2) during thermal annealing of carbon-implanted silicon, we can select the formation of a series of hydrogen and carbon-related quantum emitters, including T and Ci centers while passivating the more common G-centers. The Ci center is a telecom S-band emitter with promising optical and spin properties that consists of a single interstitial carbon atom in the silicon lattice. Density functional theory calculations show that the Ci center brightness is enhanced by several orders of magnitude in the presence of hydrogen. Fs-laser pulses locally affect the passivation or activation of quantum emitters with hydrogen for programmable formation of selected quantum emitters.

Absolute calibration of GafChromic film for very high flux laser driven ion beams.

We report on the calibration of GafChromic HD-v2 radiochromic film in the extremely high dose regime up to 100 kGy together with very high dose rates up to 7 × 1011 Gy/s. The absolute calibration was done with nanosecond ion bunches at the Neutralized Drift Compression Experiment II particle accelerator at Lawrence Berkeley National Laboratory (LBNL) and covers a broad dose dynamic range over three orders of magnitude. We then applied the resulting calibration curve to calibrate a laser driven ion experiment performed on the BELLA petawatt laser facility at LBNL. Here, we reconstructed the spatial and energy resolved distributions of the laser-accelerated proton beams. The resulting proton distribution is in fair agreement with the spectrum that was measured with a Thomson spectrometer in combination with a microchannel plate detector.

Petawatt Laser Guiding and Electron Beam Acceleration to 8 GeV in a Laser-Heated Capillary Discharge Waveguide.

Guiding of relativistically intense laser pulses with peak power of 0.85 PW over 15 diffraction lengths was demonstrated by increasing the focusing strength of a capillary discharge waveguide using laser inverse bremsstrahlung heating. This allowed for the production of electron beams with quasimonoenergetic peaks up to 7.8 GeV, double the energy that was previously demonstrated. Charge was 5 pC at 7.8 GeV and up to 62 pC in 6 GeV peaks, and typical beam divergence was 0.2 mrad.

Density characterization of discharged gas-filled capillaries through common-path two-color spectral-domain interferometry.

Electrically discharged plasma structures, typically several centimeters in length and sub-millimeter in diameter, have been applied to guide laser pulses in laser plasma accelerators and to focus ion and relativistic electron beams in compact, radially symmetric transport configurations. Knowledge of the on-axis plasma density is critical. Traditional density interferometry has been ineffective for these laser-machined structures, while group velocity delay (GVD) techniques involve combining two laser paths with corresponding alignment complexities and stability sensitivities. Here the GVD technique is advanced to a common-path two-color interferometer configuration performed in the spectral domain of a broad-bandwidth femtosecond laser. Multi-shot tracking of the phase is not required, and the common path assures improved stability. This in situ technique was validated on 15 mm long plasma structures, measuring electron densities of 1017-1018 cm-3 for various fill pressures.

Multistage coupling of independent laser-plasma accelerators.

Laser-plasma accelerators (LPAs) are capable of accelerating charged particles to very high energies in very compact structures. In theory, therefore, they offer advantages over conventional, large-scale particle accelerators. However, the energy gain in a single-stage LPA can be limited by laser diffraction, dephasing, electron-beam loading and laser-energy depletion. The problem of laser diffraction can be addressed by using laser-pulse guiding and preformed plasma waveguides to maintain the required laser intensity over distances of many Rayleigh lengths; dephasing can be mitigated by longitudinal tailoring of the plasma density; and beam loading can be controlled by proper shaping of the electron beam. To increase the beam energy further, it is necessary to tackle the problem of the depletion of laser energy, by sequencing the accelerator into stages, each powered by a separate laser pulse. Here, we present results from an experiment that demonstrates such staging. Two LPA stages were coupled over a short distance (as is needed to preserve the average acceleration gradient) by a plasma mirror. Stable electron beams from a first LPA were focused to a twenty-micrometre radius--by a discharge capillary-based active plasma lens--into a second LPA, such that the beams interacted with the wakefield excited by a separate laser. Staged acceleration by the wakefield of the second stage is detected via an energy gain of 100 megaelectronvolts for a subset of the electron beam. Changing the arrival time of the electron beam with respect to the second-stage laser pulse allowed us to reconstruct the temporal wakefield structure and to determine the plasma density. Our results indicate that the fundamental limitation to energy gain presented by laser depletion can be overcome by using staged acceleration, suggesting a way of reaching the electron energies required for collider applications.

Active Plasma Lensing for Relativistic Laser-Plasma-Accelerated Electron Beams.

Compact, tunable, radially symmetric focusing of electrons is critical to laser-plasma accelerator (LPA) applications. Experiments are presented demonstrating the use of a discharge-capillary active plasma lens to focus 100-MeV-level LPA beams. The lens can provide tunable field gradients in excess of 3000 T/m, enabling cm-scale focal lengths for GeV-level beam energies and allowing LPA-based electron beams and light sources to maintain their compact footprint. For a range of lens strengths, excellent agreement with simulation was obtained.

Multi-GeV electron beams from capillary-discharge-guided subpetawatt laser pulses in the self-trapping regime.

Multi-GeV electron beams with energy up to 4.2 GeV, 6% rms energy spread, 6 pC charge, and 0.3 mrad rms divergence have been produced from a 9-cm-long capillary discharge waveguide with a plasma density of ≈7×10¹7 cm⁻³, powered by laser pulses with peak power up to 0.3 PW. Preformed plasma waveguides allow the use of lower laser power compared to unguided plasma structures to achieve the same electron beam energy. A detailed comparison between experiment and simulation indicates the sensitivity in this regime of the guiding and acceleration in the plasma structure to input intensity, density, and near-field laser mode profile.

Measurement of the laser-pulse group velocity in plasma waveguides.

Electrically discharged plasma channels can guide laser pulses, extending the laser-plasma interaction length to many Rayleigh ranges. In applications such as the laser-plasma accelerator, the laser group velocity in the channel plays a critical role. The laser travel time (and thus the averaged group velocity) was measured through two-pulse frequency-domain interferometry and was found to depend on the on-axis plasma density and laser spot size. The data is in agreement with theory.

Low-emittance electron bunches from a laser-plasma accelerator measured using single-shot x-ray spectroscopy.

X-ray spectroscopy is used to obtain single-shot information on electron beam emittance in a low-energy-spread 0.5 GeV-class laser-plasma accelerator. Measurements of betatron radiation from 2 to 20 keV used a CCD and single-photon counting techniques. By matching x-ray spectra to betatron radiation models, the electron bunch radius inside the plasma is estimated to be ~0.1 µm. Combining this with simultaneous electron spectra, normalized transverse emittance is estimated to be as low as 0.1 mm mrad, consistent with three-dimensional particle-in-cell simulations. Correlations of the bunch radius with electron beam parameters are presented.

Long-range persistence of femtosecond modulations on laser-plasma-accelerated electron beams.

Laser plasma accelerators have produced femtosecond electron bunches with a relative energy spread ranging from 100% to a few percent. Simulations indicate that the measured energy spread can be dominated by a correlated spread, with the slice spread significantly lower. Measurements of coherent optical transition radiation are presented for broad-energy-spread beams with laser-induced density and momentum modulations. The long-range (meter-scale) observation of coherent optical transition radiation indicates that the slice energy spread is below the percent level to preserve the modulations.

Tumour hypoxia and technetium tracers: in vivo studies.

INTRODUCTION: Hypoxia is a biochemical condition where reduced oxygen partial pressure at tissue level occurs. This metabolic situation can lead to resistance to radio and chemotherapy. In malignant solid tumours, hypoxia is a common characteristic, having a great impact at biological level, being of tremendous importance for complete understanding of tumour progression. OBJECTIVES: We studied the behavior of 99mTc-HL91 in vivo, using an animal model based on Balb-c nu/nu mice with a xenotransplant of the human colorectal adenocarcinoma cell line, WiDr. MATERIAL AND METHODS: In vivo studies using an animal model of xenograft on Balb/c nu/nu nude mice were carried out. This model, allowed us to evaluate the radiopharmaceutical biodistribution and to calculate tumour/muscle ratio, acquired after 99mTc-HL91 injection. We also performed ex vivo studies, using the excised tumours to access viability and to characterize the intracellular production of reactive oxygen species and the status of mitochondrial membrane potential through flow cytometry. RESULTS AND DISCUSSION: The biodistribution after 99mTc-HL91 injection showed urinary and hepatobilliary excretion in similar proportions and tumour uptake around 4.4% of administered activity. This uptake was higher at the bigger tumours. Through flow cytometry we observed that larger tumours have a higher amount of reactive oxygen species and a decrease in mitochondrial membrane potential. CONCLUSIONS: 99mTc-HL91 allowed a non-invasive evaluation of the solid tumours oxidative state by nuclear medicine functional imaging. This information can be of high importance at the pre-treatment estimation of this type of tumours.

Wavefront-sensor-based electron density measurements for laser-plasma accelerators.

Characterization of the electron density in laser produced plasmas is presented using direct wavefront analysis of a probe laser beam. The performance of a laser-driven plasma-wakefield accelerator depends on the plasma wavelength and hence on the electron density. Density measurements using a conventional folded-wave interferometer and using a commercial wavefront sensor are compared for different regimes of the laser-plasma accelerator. It is shown that direct wavefront measurements agree with interferometric measurements and, because of the robustness of the compact commercial device, offer greater phase sensitivity and straightforward analysis, improving shot-to-shot plasma density diagnostics.

Incidence of symptomatic venous thromboembolism following hematopoietic stem cell transplantation.

BACKGROUND: The incidence of symptomatic venous thromboembolism (VTE) following hematopoietic stem cell transplantation (HSCT) is not well described, particularly with increased use of ambulatory care in the transplant setting. METHODS: A retrospective analysis involving 589 patients (382 autologous HSCT, 207 allogeneic HSCT) undergoing transplantation between 2000 and 2005 in a single Canadian institution was undertaken to identify the incidence of proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) in HSCT patients. RESULTS: The total 1-year incidence of symptomatic VTE was 3.7% [95% confidence interval (CI) 2.5-5.6]. Among the HSCT patients, 7/589 (1.2%, 95% CI 0.6-2.4) developed symptomatic non-catheter-related VTE following HSCT (four PE and three DVT). All VTE events occurred after hematopoietic engraftment. Patients undergoing autologous HSCT did not receive thromboprophylaxis, whereas most patients undergoing allogeneic HSCT (79.7%) received enoxaparin 20 mg daily for the prevention of veno-occlusive disease of the liver, starting 6 +/- 3 days before transplantation for a mean of 22 +/- 14 days. CONCLUSION: HSCT patients have a high incidence of VTE. Thromboprophylaxis should potentially be considered in these patients. However, future studies assessing the risk and benefits of thromboprophylaxis are needed in this specific population.

Halogen atom effect on photophysical and photodynamic characteristics of derivatives of 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin.

Brominated and iodinated derivatives of 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin were synthesised directly from the corresponding aldehydes. Photophysical and photochemical properties, singlet oxygen formation quantum yields, photobleaching and log P were measured. Cellular uptake measurements and cytotoxicity assays on WiDr and A375 tumour cell lines were performed. 5,10,15,20-Tetrakis(2-bromo-5-hydroxyphenyl)porphyrin showed the best cytotoxicity with values of IC(50) of 113 nM over WiDr cells and 52nM over A375 cells.

Laser-driven acceleration of electrons in a partially ionized plasma channel.

The generation of quasimonoenergetic electron beams, with energies up to 200 MeV, by a laser-plasma accelerator driven in a hydrogen-filled capillary discharge waveguide is investigated. Injection and acceleration of electrons is found to depend sensitively on the delay between the onset of the discharge current and the arrival of the laser pulse. A comparison of spectroscopic and interferometric measurements suggests that injection is assisted by laser ionization of atoms or ions within the channel.

Transverse interferometry of a hydrogen-filled capillary discharge waveguide.

Transverse interferometric measurements are presented of the plasma channel formed in a hydrogen-filled capillary discharge waveguide recently used to generate 1 GeV electrons in a laser-driven plasma accelerator for the first time. The measurements were found to be in good agreement with nonlocal thermal equilibrium simulations, but showed significant differences with the results of a quasistatic model developed by Bobrova et al. [Phys. Rev. E. 65, 016407 (2001)]. The measurements are used to determine scaling laws for the axial electron density and matched spot size of the plasma channel, enabling optimization of the channel to specific applications.

Fractionated stereotactic conformal radiotherapy for secreting and nonsecreting pituitary adenomas.

OBJECTIVE: To assess the medium-term outcome in a cohort of patients with residual or recurrent pituitary adenoma treated with fractionated stereotactic conformal radiotherapy (SCRT). PATIENTS AND METHODS: Ninety-two patients (median age 50 years) with a residual or recurrent nonfunctioning (67) or a secreting (25) pituitary adenoma were treated between 1995 and 2003. Eighteen patients had a GH-secreting, five PRL-secreting and two an ACTH-secreting pituitary adenoma. Vision was impaired in 39 patients, with visual field deficit (35) and/or reduced visual acuity (25). Sixty-four patients had partial or complete hypopituitarism before SCRT. The treatment was delivered stereotactically by four noncoplanar conformal fixed fields using a 6-MV linear accelerator to a dose of 45 Gy in 25 fractions. RESULTS: At a median follow-up of 32 months (range 4-108) the 1, 3 and 5 years actuarial progression-free survival is 99%, 98% and 98%, and overall survival is 98%. Three patients recurred 5 months, 1 year and 9 years after SCRT requiring surgery. In secreting adenomas, hormone levels declined progressively, becoming normal in more than a third of patients with GH-secreting and PRL-secreting pituitary tumours. 50% of baseline GH level was achieved in just under 2 years. The treatment was well tolerated with minimal acute toxicity. Hypopituitarism was the most common long-term effect; 22% of patients had worsening of pituitary function. One patient developed unilateral quadrantopia without tumour progression. CONCLUSION: SCRT as a high-precision technique of localized irradiation achieves tumour and hormone control of pituitary adenomas comparable with previously published data on the efficacy of conventional radiotherapy. Despite the potential advantage of reducing the volume of normal brain irradiated, the theoretical benefit over conventional radiotherapy in terms of the reduction in long-term morbidity has not yet been demonstrated and requires longer follow-up. Potential effect on long-term cognitive function has not been tested.

Neoadjuvant phase II multicentre study of new agents in patients with malignant glioma after minimal surgery. Report of a cohort of 187 patients treated with temozolomide.

BACKGROUND: The aim of this study was to assess the efficacy of new agents in patients with malignant glioma in a neoadjuvant setting not confounded by surgery. The first study of neoadjuvant temozolomide aimed to provide a benchmark for future evaluation of new treatments. PATIENTS AND METHODS: This was a multicentre phase II study of chemotherapy in patients with histologically verified glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA) who had undergone biopsy alone. Patients were planned to receive two cycles of temozolomide at 200 mg/m(2) orally daily for 5 days at a 28-day interval prior to radiotherapy. Response was assessed by two central observers on pre- and post-chemotherapy enhanced scans using bi-dimensional criteria and as progression-free survival (PFS) at the time of second assessment prior to radiotherapy. Withdrawal from the study due to worsening clinical condition was, in the absence of second imaging, assessed as progressive disease. Survival and quality of life (QOL) were secondary endpoints. RESULTS: Between August 1999 and June 2002, 188 patients from 15 UK and two Italian centres were entered into the study and 187 were analysed. Overall, 162 patients were assessable for response; seven had partial and 25 had minimal response. The objective response rate was 20% [95% confidence interval (CI) 14-26%] and PFS prior to commencing radiotherapy was 64% (95% CI 57-72%). The median survival was 10 months, and 1-year survival 41%. The median survival of responders was 16 months compared to 3 months in patients with progressive disease (P <0.001 on multivariate analysis). CONCLUSION: The phase II study design of primary chemotherapy in patients with malignant glioma following biopsy alone is feasible and provides as objective a method of assessment of efficacy as is currently available. The baseline data on temozolomide provide a benchmark for assessment of efficacy of other agents and combinations.

Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma: update after an additional 10 years.

We assessed the risk of second brain tumors in a cohort of patients with pituitary adenoma treated with conservative surgery and external beam radiotherapy. Four hundred and twenty-six patients (United Kingdom residents) with pituitary adenomas received radiotherapy at the Royal Marsden Hospital (RMH) between 1962 and 1994. They were followed up for 5749 person-years. The cumulative incidence of second intracranial tumors and systemic malignancy was compared with population incidence rates through the Thames Cancer Registry and the National Health Service Central Register (previously OPCS) to record death and the potential causes. Eleven patients developed a second brain tumor, including five meningiomas, four high grade astrocytomas, one meningeal sarcoma, and one primitive neuroectodermal tumor. The cumulative risk of second brain tumors was 2.0% [95% confidence interval (CI), 0.9-4.4%] at 10 yr and 2.4% (95% CI, 1.2-5.0%) at 20 yr, measured from the date of radiotherapy. The relative risk of second brain tumor compared with the incidence in the normal population was 10.5 (95% CI, 4.3-16.7). The relative risk was 7.0 for neuroepithelial and 24.3 for meningeal tumors. The relative risks were 24.2 (95% CI, 4.8-43.5), 2.9 (95% CI, 0-8.5), and 28.6 (95% CI, 0.6-56.6) during the intervals 5-9, 10-19, and more than 20 yr after radiotherapy (four cases occurred >20 yr after treatment). There was no evidence of excess risk of second systemic malignancy. An additional 10-yr update confirmed our previous report of an increased risk of second brain tumors in patients with pituitary adenoma treated with surgery and radiotherapy. The 2.4% risk at 20 yr remains low and should not preclude the use of radiotherapy as an effective treatment option. However, an increased risk of second brain tumors continues beyond 20 and 30 yr after treatment.