Characterisation of microbunching instability with 2D Fourier analysis.

The optimal performance of high-brightness free-electron lasers (FELs) is limited by the microbunching instability, which can cause variations in both the slice energy spread and longitudinal profile of electron beams. In this paper, we perform 2D Fourier analysis of the full bunch longitudinal phase space, such that modulations in both planes can be studied simultaneously. Unlike the standard 1D analysis, this method is able to reveal modulations in a folded phase space, which would otherwise remain uncovered. Additionally, the plasma oscillation between energy and density modulations is also revealed by this method. The damping of the microbunching instability, through the use of a laser heater, is also analysed with this technique. We confirm a mitigation of the amplitude of modulation and a red-shift of the microbunching frequency as the energy spread added increases. As an outcome of this work, a systematic experimental comparison of the development of the instability in the presence of different compression schemes is here presented for the first time.

Nanoscale transient gratings excited and probed by extreme ultraviolet femtosecond pulses.

Advances in developing ultrafast coherent sources operating at extreme ultraviolet (EUV) and x-ray wavelengths allow the extension of nonlinear optical techniques to shorter wavelengths. Here, we describe EUV transient grating spectroscopy, in which two crossed femtosecond EUV pulses produce spatially periodic nanoscale excitations in the sample and their dynamics is probed via diffraction of a third time-delayed EUV pulse. The use of radiation with wavelengths down to 13.3 nm allowed us to produce transient gratings with periods as short as 28 nm and observe thermal and coherent phonon dynamics in crystalline silicon and amorphous silicon nitride. This approach allows measurements of thermal transport on the ~10-nm scale, where the two samples show different heat transport regimes, and can be applied to study other phenomena showing nontrivial behaviors at the nanoscale, such as structural relaxations in complex liquids and ultrafast magnetic dynamics.

The German Hodgkin Study Group risk model is useful for Hodgkin lymphoma patients receiving radiotherapy after autologous stem cell transplant.

PURPOSE: To apply the German Hodgkin Study Group (GHSG) risk model in patients with recurrent/refractory Hodgkin lymphoma receiving involved-field radiotherapy after autologous stem cell transplantation. MATERIAL AND METHODS: The study consisted in the retrospective analysis of 30 consecutive patients with recurrent/refractory Hodgkin lymphoma who received involved-field radiotherapy after autologous stem cell transplantation. Our policy was of adding involved-field radiotherapy for patients with positive PET scan before autologous stem cell transplantation (23 out of 30 patients, 77%), and/or irradiating sites of bulky disease at relapse (11 out of 30 patients, 37%). Patients were stratified into four risk groups according to the presence of the five clinical risk factors identified by the GHSG; (1) stage IV disease; (2) time to relapse≤3 months; (3) ECOG-PS≥1; (4) bulk≥5cm; and (5) inadequate response to salvage chemotherapy. RESULTS: The median interval from autologous stem cell transplantation to involved-field radiotherapy was 3 months (range, 1-7 months), and the median involved-field radiotherapy dose was 35Gy (range, 12-40Gy). At a median follow-up of 35 months (range, 1-132 months), the 2-year progression-free survival in the entire series was 60%. When examining the four different GHSG risk groups, the progression-free survival rate at 2 years was 86%, 83%, 50%, and 36% for patients with score=0, score=1, score=2, and score=3 to 5, respectively (P=0,01). Among the 12 patients havingat leastthree risk factors who underwent thoracic involved-field radiotherapy, three (25%) developed pneumonitis. CONCLUSION: The adoption of the GHSG risk model at the time of recurrence/progression is a useful prognostic tool to select patients with Hodgkin lymphoma for consolidative involved-field radiotherapy after autologous stem cell transplantation.

Coherent THz Emission Enhanced by Coherent Synchrotron Radiation Wakefield.

We demonstrate that emission of coherent transition radiation by a ∼1 GeV energy-electron beam passing through an Al foil is enhanced in intensity and extended in frequency spectral range, by the energy correlation established along the beam by coherent synchrotron radiation wakefield, in the presence of a proper electron optics in the beam delivery system. Analytical and numerical models, based on experimental electron beam parameters collected at the FERMI free electron laser (FEL), predict transition radiation with two intensity peaks at ∼0.3 THz and ∼1.5 THz, and extending up to 8.5 THz with intensity above 20 dB w.r.t. the main peak. Up to 80-µJ pulse energy integrated over the full bandwidth is expected at the source, and in agreement with experimental pulse energy measurements. By virtue of its implementation in an FEL beam dump line, this work promises dissemination of user-oriented multi-THz beamlines parasitic and self-synchronized to EUV and x-ray FELs.

Soft X-Ray Second Harmonic Generation as an Interfacial Probe.

Nonlinear optical processes at soft x-ray wavelengths have remained largely unexplored due to the lack of available light sources with the requisite intensity and coherence. Here we report the observation of soft x-ray second harmonic generation near the carbon K edge (∼284 eV) in graphite thin films generated by high intensity, coherent soft x-ray pulses at the FERMI free electron laser. Our experimental results and accompanying first-principles theoretical analysis highlight the effect of resonant enhancement above the carbon K edge and show the technique to be interfacially sensitive in a centrosymmetric sample with second harmonic intensity arising primarily from the first atomic layer at the open surface. This technique and the associated theoretical framework demonstrate the ability to selectively probe interfaces, including those that are buried, with elemental specificity, providing a new tool for a range of scientific problems.

Passive Linearization of the Magnetic Bunch Compression Using Self-Induced Fields.

In linac-driven free-electron lasers, colliders, and energy recovery linacs, a common way to compress the electron bunch to kiloampere level is based upon the implementation of a magnetic dispersive element that converts particle energy deviation into a path-length difference. Nonlinearities of such a process are usually compensated by enabling a high harmonic rf structure properly tuned in amplitude and phase. This approach is however not straightforward, e.g., in C-band and X-band linacs. In this Letter we demonstrate that the longitudinal self-induced field excited by the electron beam itself is able to linearize the compression process without any use of high harmonic rf structure. The method is implemented at the FERMI linac, with the resulting high quality beam used to drive the seeded free-electron laser during user experiments.

Stereotactic body radiation therapy and intensity modulated radiation therapy induce different plasmatic cytokine changes in non-small cell lung cancer patients: a pilot study

Purpose: To assess kinetics of plasmatic cytokines during radiation therapy (RT) for locally advanced and early-stage non-small cell lung cancer (NSCLC). Methods: This prospective study was conducted on 15 early-stage NSCLC underwent to extreme hypofractionated regimen (52 Gy in 8 fractions) with stereotactic body RT (SBRT), and 13 locally advanced NSCLC underwent to radical moderated hypofractionated regimen (60 Gy in 25 fractions) with intensity modulated RT (IMRT). For patients undergoing SBRT, peripheral blood samples were collected on the first day of SBRT (TFd), the last day (TLd) and 45 days (T45d) after the end of SBRT. For patients undergoing IMRT, blood samples were collected at: TFd, 2 weeks (T2w), 4 weeks (T4w), TLd, and T45d. The following cytokines were measured: IL-1, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17A, EGF, FGF-2, INF-c, MIP-1a, MIP-1b, TGF-a, TNF-a, and VEGF. Cytokine levels measured in different RT time and compared. Results: No difference in baseline levels of cytokines was documented between patient radiation approaches (except for MIP-1a). For SBRT patients, a mean reduction of IL-10 and IL-17 plasma level was documented between TLd and TFd, respectively (p < 0.05). For IMRT patients, a statistically significant (p < 0.05) mean plasma level reduction was documented between T4w and TFd for all the following cytokines: IL-1, IL-1ra, IL-2, IL-12, FGF-2, MIP-1α, MIP-1β, TGF-α, TNF-α, VEGF Conclusions: SBRT and IMRT induce different plasmatic cytokine changes in NSCLC patients, supporting hypothesis that RT regimes of dose schedules and techniques have different impacts on the host immune response

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Stereotactic body radiation therapy and intensity modulated radiation therapy induce different plasmatic cytokine changes in non-small cell lung cancer patients: a pilot study.

PURPOSE: To assess kinetics of plasmatic cytokines during radiation therapy (RT) for locally advanced and early-stage non-small cell lung cancer (NSCLC). METHODS: This prospective study was conducted on 15 early-stage NSCLC underwent to extreme hypofractionated regimen (52 Gy in 8 fractions) with stereotactic body RT (SBRT), and 13 locally advanced NSCLC underwent to radical moderated hypofractionated regimen (60 Gy in 25 fractions) with intensity modulated RT (IMRT). For patients undergoing SBRT, peripheral blood samples were collected on the first day of SBRT (TFd), the last day (TLd) and 45 days (T45d) after the end of SBRT. For patients undergoing IMRT, blood samples were collected at: TFd, 2 weeks (T2w), 4 weeks (T4w), TLd, and T45d. The following cytokines were measured: IL-1, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17A, EGF, FGF-2, INF-γ, MIP-1α, MIP-1ß, TGF-α, TNF-α, and VEGF. Cytokine levels measured in different RT time and compared. RESULTS: No difference in baseline levels of cytokines was documented between patient radiation approaches (except for MIP-1α). For SBRT patients, a mean reduction of IL-10 and IL-17 plasma level was documented between TLd and TFd, respectively (p < 0.05). For IMRT patients, a statistically significant (p < 0.05) mean plasma level reduction was documented between T4w and TFd for all the following cytokines: IL-1, IL-1ra, IL-2, IL-12, FGF-2, MIP-1α, MIP-1ß, TGF-α, TNF-α, VEGF. CONCLUSIONS: SBRT and IMRT induce different plasmatic cytokine changes in NSCLC patients, supporting hypothesis that RT regimes of dose schedules and techniques have different impacts on the host immune response.

The FERMI free-electron lasers.

FERMI is a seeded free-electron laser (FEL) facility located at the Elettra laboratory in Trieste, Italy, and is now in user operation with its first FEL line, FEL-1, covering the wavelength range between 100 and 20 nm. The second FEL line, FEL-2, a high-gain harmonic generation double-stage cascade covering the wavelength range 20-4 nm, has also completed commissioning and the first user call has been recently opened. An overview of the typical operating modes of the facility is presented.

Normal tissue complication probability models for severe acute radiological lung injury after radiotherapy for lung cancer.

PURPOSE: To derive Normal Tissue Complication Probability (NTCP) models for severe patterns of early radiological radiation-induced lung injury (RRLI) in patients treated with radiotherapy (RT) for lung tumors. Second, derive threshold doses and optimal doses for prediction of RRLI to be used in differential diagnosis of tumor recurrence from RRLI during follow-up. METHODS AND MATERIALS: Lyman-EUD (LEUD), Logit-EUD (LogEUD), relative seriality (RS) and critical volume (CV) NTCP models, with DVH corrected for fraction size, were used to model the presence of severe early RRLI in follow-up CTs. The models parameters, including α/ß, were determined by fitting data from forty-five patients treated with IMRT for lung cancer. Models were assessed using Akaike information criterion (AIC) and area under receiver operating characteristic curve (AUC). Threshold doses for risk of RRLI and doses corresponding to the optimal point of the receiver operating characteristic (ROC) curve were determined. RESULTS: The α/ßs obtained with different models were 2.7-3.2 Gy. The thresholds and optimal doses curves were EUDs of 3.2-7.8 Gy and 15.2-18.1 Gy with LEUD, LogEUD and RS models, and µd of 0.013 and 0.071 with the CV model. NTCP models had AUCs significantly higher than 0.5. Occurrence and severity of RRLI were correlated with patients' values of EUD and µd. CONCLUSIONS: The models and dose levels derived can be used in differential diagnosis of tumor recurrence from RRLI in patients treated with RT. Cross validation is needed to prove prediction performance of the model outside the dataset from which it was derived.

Experimental demonstration of electron longitudinal-phase-space linearization by shaping the photoinjector laser pulse.

Control of the electron-beam longitudinal-phase-space distribution is of crucial importance in a number of accelerator applications, such as linac-driven free-electron lasers, colliders and energy recovery linacs. Some longitudinal-phase-space features produced by nonlinear electron beam self- fields, such as a quadratic energy chirp introduced by geometric longitudinal wakefields in radio-frequency (rf) accelerator structures, cannot be compensated by ordinary tuning of the linac rf phases nor corrected by a single high harmonic accelerating cavity. In this Letter we report an experimental demonstration of the removal of the quadratic energy chirp by properly shaping the electron beam current at the photoinjector. Specifically, a longitudinal ramp in the current distribution at the cathode linearizes the longitudinal wakefields in the downstream linac, resulting in a flat electron current and energy distribution. We present longitudinal-phase-space measurements in this novel configuration compared to those typically obtained without longitudinal current shaping at the FERMI linac.

Role of serotonin 1A receptors in the median raphe nucleus on the behavioral consequences of forced swim stress.

Despite the intense research on the neurobiology of stress, the role of serotonin (5-HT)1A receptors still remains to be elucidated. In the hippocampus, post-synaptic 5-HT1A receptors activation induces anxiolytic effects in animals previously exposed to stressful situations. However, little is known about somatodendritic 5-HT1A receptors in the median raphe nucleus (MRN). Therefore, the aim of this study was to investigate the role of 5-HT1A receptors located in the MRN in rats exposed to forced swim stress. After recovering from surgery, rats were forced to swim for 15 min in a cylinder. Intra-MRN injections of saline, 8-OH-DPAT (3 nmol/0.2 µL) and/or WAY-100635 (0.3 nmol/0.2 µL) were performed immediately before or after pre-exposure or 24 h later (immediately before test). Non-stressed rats received the same treatment 24 h or 10 min before test. Our data showed that 8-OH-DPAT increased latency to display immobility while decreasing time spent immobile in almost all experimental conditions. These effects were not prevented by previous treatment with WAY-100635. No effects of different treatments were described in non-stressed animals. Taken together, our data suggest that in addition to activation of 5-HT1A, 5-HT7 receptors may also be involved in the behavioural consequences of exposure to swim stress.

Two-colour pump-probe experiments with a twin-pulse-seed extreme ultraviolet free-electron laser.

Exploring the dynamics of matter driven to extreme non-equilibrium states by an intense ultrashort X-ray pulse is becoming reality, thanks to the advent of free-electron laser technology that allows development of different schemes for probing the response at variable time delay with a second pulse. Here we report the generation of two-colour extreme ultraviolet pulses of controlled wavelengths, intensity and timing by seeding of high-gain harmonic generation free-electron laser with multiple independent laser pulses. The potential of this new scheme is demonstrated by the time evolution of a titanium-grating diffraction pattern, tuning the two coherent pulses to the titanium M-resonance and varying their intensities. This reveals that an intense pulse induces abrupt pattern changes on a time scale shorter than hydrodynamic expansion and ablation. This result exemplifies the essential capabilities of the jitter-free multiple-colour free-electron laser pulse sequences to study evolving states of matter with element sensitivity.

Multimodality approach in extra cervical locally advanced cervical cancer: chemoradiation, surgery and intra-operative radiation therapy. A phase II trial.

BACKGROUND: The goal of this study was to determine the rational of radical surgery with intra-operative high-dose radiotherapy after chemoradiation (RT-CT) in extra cervical locally advanced cervical cancer (LACC) patients. METHODS: Between 2000 and 2007, 42 LACC (stage IIA bulky-IVA) patients were treated at the Gynecologic Oncology Unit of the C.R.O. of Aviano in a Phase II Clinical Trial. Radiotherapy was administered to the whole pelvic region (50.4 Gy in 28 fractions) in combination with cisplatin (60 mg/mq) plus 5FU (750 mg/mq for 4 days) on first and fifth week of RT. Radical surgery with Intra-Operative Radiation Therapy (IORT) was performed 6-8 weeks after the end of RT-CT treatment. RESULTS: After RT-CT, 35/42 patients (83%) underwent radical surgery and IORT treatment. At pathologic examination 8/35 (23%) patients showed complete response, while the rest (27/35) had residual disease either microscopic (17/27) or gross (10/27). The 5-year disease free survival (DFS) and the 5-year overall survival (OS) were 46% and 49% respectively. There were significant better DFS and OS when residual tumor was absent or limited to the cervix, respectively 78% versus 16% and 81% versus 20% (p < 0.001). All recurrences occurred within 24 months from treatment. CONCLUSIONS: RT-CT followed by surgery and IORT in LACC patients seems to be active in a subgroup of patients with pathological complete response to treatment or partial response with residual tumor limited to the cervix.

Generation of ultrashort coherent vacuum ultraviolet pulses using electron storage rings: a new bright light source for experiments.

We demonstrate for the first time that seeded harmonic generation on electron storage rings can produce coherent optical pulses in the vacuum ultraviolet spectral range. The experiment is performed at Elettra, where coherent pulses are generated at 132 nm, with a duration of about 100 fs. The light source has a repetition rate of 1 kHz and adjustable polarization; it is very bright, with a peak power several orders of magnitude above that of spontaneous synchrotron radiation. Owing to high stability, the source is used in a test photoemission electron microscopy experiment. We anticipate that seeded harmonic generation on storage rings can lead to unprecedented developments in time-resolved femtosecond spectroscopy and microscopy.

Experimental characterization of nonlinear harmonic generation in planar and helical undulators.

We present an experimental characterization of the process of coherent harmonic generation in single-pass free electron lasers. The harmonic radiation is obtained by seeding the electron beam stored in the Elettra storage ring with a Ti:sapphire laser. Different methods for generating harmonics are compared between them, and a detailed characterization of the emitted light is performed for different polarizations. Our results also contribute to the debate about the possible presence of a coherent on-axis signal in helical undulators. In this respect, we provide an experimental confirmation of recent theoretical studies that predict no coherent on-axis signal.