Multi-GeV Electron Acceleration in Wakefields Strongly Driven by Oversized Laser Spots.

Experiments were performed on laser wakefield acceleration in the highly nonlinear regime. With laser powers P<250 TW and using an initial spot size larger than the matched spot size for guiding, we were able to accelerate electrons to energies E_{max}>2.5 GeV, in fields exceeding 500 GV m^{-1}, with more than 80 pC of charge at energies E>1 GeV. Three-dimensional particle-in-cell simulations show that using an oversized spot delays injection, avoiding beam loss as the wakefield undergoes length oscillation. This enables injected electrons to remain in the regions of highest accelerating fields and leads to a doubling of energy gain as compared to results from using half the focal length with the same laser.

Author Correction: Laser-wakefield accelerators for high-resolution X-ray imaging of complex microstructures.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Laser-wakefield accelerators for high-resolution X-ray imaging of complex microstructures.

Laser-wakefield accelerators (LWFAs) are high acceleration-gradient plasma-based particle accelerators capable of producing ultra-relativistic electron beams. Within the strong focusing fields of the wakefield, accelerated electrons undergo betatron oscillations, emitting a bright pulse of X-rays with a micrometer-scale source size that may be used for imaging applications. Non-destructive X-ray phase contrast imaging and tomography of heterogeneous materials can provide insight into their processing, structure, and performance. To demonstrate the imaging capability of X-rays from an LWFA we have examined an irregular eutectic in the aluminum-silicon (Al-Si) system. The lamellar spacing of the Al-Si eutectic microstructure is on the order of a few micrometers, thus requiring high spatial resolution. We present comparisons between the sharpness and spatial resolution in phase contrast images of this eutectic alloy obtained via X-ray phase contrast imaging at the Swiss Light Source (SLS) synchrotron and X-ray projection microscopy via an LWFA source. An upper bound on the resolving power of 2.7 ± 0.3 µm of the LWFA source in this experiment was measured. These results indicate that betatron X-rays from laser wakefield acceleration can provide an alternative to conventional synchrotron sources for high resolution imaging of eutectics and, more broadly, complex microstructures.

Single-Shot Multi-keV X-Ray Absorption Spectroscopy Using an Ultrashort Laser-Wakefield Accelerator Source.

Single-shot absorption measurements have been performed using the multi-keV x rays generated by a laser-wakefield accelerator. A 200 TW laser was used to drive a laser-wakefield accelerator in a mode which produced broadband electron beams with a maximum energy above 1 GeV and a broad divergence of ≈15 mrad FWHM. Betatron oscillations of these electrons generated 1.2±0.2×10^{6} photons/eV in the 5 keV region, with a signal-to-noise ratio of approximately 300∶1. This was sufficient to allow high-resolution x-ray absorption near-edge structure measurements at the K edge of a titanium sample in a single shot. We demonstrate that this source is capable of single-shot, simultaneous measurements of both the electron and ion distributions in matter heated to eV temperatures by comparison with density functional theory simulations. The unique combination of a high-flux, large bandwidth, few femtosecond duration x-ray pulse synchronized to a high-power laser will enable key advances in the study of ultrafast energetic processes such as electron-ion equilibration.

A spectrometer for ultrashort gamma-ray pulses with photon energies greater than 10 MeV.

We present a design for a pixelated scintillator based gamma-ray spectrometer for non-linear inverse Compton scattering experiments. By colliding a laser wakefield accelerated electron beam with a tightly focused, intense laser pulse, gamma-ray photons up to 100 MeV energies and with few femtosecond duration may be produced. To measure the energy spectrum and angular distribution, a 33 × 47 array of cesium-iodide crystals was oriented such that the 47 crystal length axis was parallel to the gamma-ray beam and the 33 crystal length axis was oriented in the vertical direction. Using an iterative deconvolution method similar to the YOGI code, modeling of the scintillator response using GEANT4 and fitting to a quantum Monte Carlo calculated photon spectrum, we are able to extract the gamma ray spectra generated by the inverse Compton interaction.

Experimental Observation of a Current-Driven Instability in a Neutral Electron-Positron Beam.

We report on the first experimental observation of a current-driven instability developing in a quasineutral matter-antimatter beam. Strong magnetic fields (≥1 T) are measured, via means of a proton radiography technique, after the propagation of a neutral electron-positron beam through a background electron-ion plasma. The experimentally determined equipartition parameter of ε_{B}≈10^{-3} is typical of values inferred from models of astrophysical gamma-ray bursts, in which the relativistic flows are also expected to be pair dominated. The data, supported by particle-in-cell simulations and simple analytical estimates, indicate that these magnetic fields persist in the background plasma for thousands of inverse plasma frequencies. The existence of such long-lived magnetic fields can be related to analog astrophysical systems, such as those prevalent in lepton-dominated jets.

Direct Observation of the Injection Dynamics of a Laser Wakefield Accelerator Using Few-Femtosecond Shadowgraphy.

We present few-femtosecond shadowgraphic snapshots taken during the nonlinear evolution of the plasma wave in a laser wakefield accelerator with transverse synchronized few-cycle probe pulses. These snapshots can be directly associated with the electron density distribution within the plasma wave and give quantitative information about its size and shape. Our results show that self-injection of electrons into the first plasma-wave period is induced by a lengthening of the first plasma period. Three-dimensional particle-in-cell simulations support our observations.

Laser-wakefield accelerators as hard x-ray sources for 3D medical imaging of human bone.

A bright µm-sized source of hard synchrotron x-rays (critical energy Ecrit > 30 keV) based on the betatron oscillations of laser wakefield accelerated electrons has been developed. The potential of this source for medical imaging was demonstrated by performing micro-computed tomography of a human femoral trabecular bone sample, allowing full 3D reconstruction to a resolution below 50 µm. The use of a 1 cm long wakefield accelerator means that the length of the beamline (excluding the laser) is dominated by the x-ray imaging distances rather than the electron acceleration distances. The source possesses high peak brightness, which allows each image to be recorded with a single exposure and reduces the time required for a full tomographic scan. These properties make this an interesting laboratory source for many tomographic imaging applications.

The aggregation of early-onset melanoma in young Western Australian families.

BACKGROUND: Few studies have examined the familial aggregation of melanoma or its co-aggregation with other cancers using whole-population based designs. This study aimed to investigate aggregation patterns in young Western Australian families, using population-based linked health data to identify individuals born in Western Australia between 1974 and 2007, their known relatives, and all incident cancer diagnoses within the resulting 1,506,961 individuals. METHODS: Cox proportional hazards regression models were used to compare the risk of melanoma for first-degree relatives of melanoma cases to that for first-degree relatives of controls, with bootstrapping used to account for correlations within families. The risk of (i) developing melanoma based on the number of first-degree relatives with other cancers, and (ii) developing non-melanoma cancers based on the number of first-degree relatives diagnosed with melanoma was also investigated. RESULTS: First-degree relatives of melanoma cases had a significantly greater incidence of melanoma than first-degree relatives of individuals not affected with melanoma (Hazard Ratio (HR)=3.58, 95% bootstrap confidence interval (CI): 2.43-5.43). Sensitivity analyses produced a higher hazard ratio estimate when restricted to melanoma cases diagnosed before 40 years of age (HR=3.77, bootstrap 95% CI: 2.49-6.39) and a lower estimate when only later-onset cases (>40 years) were considered (HR=2.45, bootstrap 95% CI: 1.23-4.82). No significant evidence was found for co-aggregation between melanoma and any other cancers. CONCLUSIONS: Results indicated a strong familial basis of melanoma, with the higher than expected hazard ratio observed likely to reflect early-age at onset cases in this young cohort, supported by the results of the sensitivity analyses. Exploratory analyses suggested that the determinants of melanoma causing the observed aggregation within families may be independent of other malignancies, although these analyses were limited by the young age of the sample. Determining familial aggregation patterns will provide valuable knowledge regarding improved clinical risk prediction and the underlying biological mechanisms of melanoma and other cancers.

Generation of neutral and high-density electron-positron pair plasmas in the laboratory.

Electron-positron pair plasmas represent a unique state of matter, whereby there exists an intrinsic and complete symmetry between negatively charged (matter) and positively charged (antimatter) particles. These plasmas play a fundamental role in the dynamics of ultra-massive astrophysical objects and are believed to be associated with the emission of ultra-bright gamma-ray bursts. Despite extensive theoretical modelling, our knowledge of this state of matter is still speculative, owing to the extreme difficulty in recreating neutral matter-antimatter plasmas in the laboratory. Here we show that, by using a compact laser-driven setup, ion-free electron-positron plasmas with unique characteristics can be produced. Their charge neutrality (same amount of matter and antimatter), high-density and small divergence finally open up the possibility of studying electron-positron plasmas in controlled laboratory experiments.

Ultrahigh Brilliance Multi-MeV γ-Ray Beams from Nonlinear Relativistic Thomson Scattering.

We report on the generation of a narrow divergence (θ_{γ}<2.5 mrad), multi-MeV (E_{max}≈18 MeV) and ultrahigh peak brilliance (>1.8×10^{20} photons s^{-1} mm^{-2} mrad^{-2} 0.1% BW) γ-ray beam from the scattering of an ultrarelativistic laser-wakefield accelerated electron beam in the field of a relativistically intense laser (dimensionless amplitude a_{0}≈2). The spectrum of the generated γ-ray beam is measured, with MeV resolution, seamlessly from 6 to 18 MeV, giving clear evidence of the onset of nonlinear relativistic Thomson scattering. To the best of our knowledge, this photon source has the highest peak brilliance in the multi-MeV regime ever reported in the literature.

The association of host and genetic melanoma risk factors with Breslow thickness in the Western Australian Melanoma Health Study.

BACKGROUND: Breslow thickness is the most important predictor of survival in localized malignant melanoma. A number of melanoma risk factors have been shown to be associated with Breslow thickness; however, the role of genetic loci has been little investigated to date. OBJECTIVES: To investigate the association of known melanoma susceptibility genetic loci with Breslow thickness. METHODS: Participants were 800 individuals from the Western Australian Melanoma Health Study who completed a questionnaire and provided a DNA sample. Genetic association analyses between single-nucleotide polymorphisms (SNPs) from 15 candidate melanoma susceptibility genes and Breslow thickness were performed, controlling for relevant covariates. RESULTS: Older age at diagnosis and absence of naevi were associated with increased Breslow thickness. Following adjustment for multiple testing, no SNPs were significantly associated with Breslow thickness. CONCLUSIONS: Associations observed between Breslow thickness and age and naevi reinforce current knowledge. Some evidence of shared genetic determinants between melanoma risk and Breslow thickness was found. Further studies are required to confirm this finding.

Association of TGFß1 and clinical factors with scar outcome following melanoma excision.

All patients with primary cutaneous malignant melanoma undergo surgical excision to remove the tumour, resulting in scar formation. There is marked variation in the aesthetic appearance of scars following surgery but limited knowledge about the genetic factors affecting non-keloid, surgical scar outcomes. This study aimed to investigate the role of known clinical factors and genetic polymorphisms in pigmentation and wound repair genes in non-keloid scar outcome, following melanoma excision. Participants were 202 cases who underwent a standardized scar assessment following surgical melanoma excision and provided a DNA sample. Genetic association analyses between single nucleotide polymorphisms (SNPs) from 24 candidate genes and scar outcome data were performed, controlling for relevant clinical factors. Following adjustment for multiple testing, SNP rs8110090 in TGFß1 was significantly associated with both the primary scar outcome (a combination score reflecting vascularity, height and pliability, p = 0.0002, q = 0.01) and the secondary scar outcome (a combination score reflecting vascularity, height, pliability and pigmentation, p = 0.0002, q = 0.006). The minor allele G was associated with a poorer scar outcome. Younger age, time elapsed since excision, absence of kidney failure and eczema, presence of thyroid problems and infection were also associated with poorer scar outcome and were adjusted for in the final model, along with scar site. Results from this study suggest that genes involved in wound healing may play a role in determining scar outcome. Associations observed between scar outcome and clinical factors reinforce current clinical knowledge regarding factors affecting scarring. Replication studies in larger samples are warranted and will improve our understanding of the underlying mechanisms of scarring, potentially help to identify patients at risk of poor scar outcomes.

A prototype chopper for synchrotron time-resolved crystallographic measurements.

A mechanical x-ray chopper has been designed to perform microsecond time-resolved crystallographic studies at the DIAMOND synchrotron I19 beamline. It consists of two asymmetric absorbers rotating synchronously at frequencies from 0 to 50 Hz in the same direction around a rotation axis that is parallel to the x-ray beam. The duration of the x-ray pulses produced by the chopper is determined by the relative phase between the two blades, which can be adjusted. The chopper system presented in this paper offers a time resolution suitable for conducting in situ experiments that afford the crystal structure of materials while in their transient (>10 micros) photoactivated excited states.

The structure of graphite oxide: investigation of its surface chemical groups.

The structure of graphite oxide (GO) has been systematically studied using various tools such as SEM, TEM, XRD, Fourier transform infrared spectroscopy (FT-IR), X-ray photoemission spectroscopy (XPS), (13)C solid-state NMR, and O K-edge X-ray absorption near edge structure (XANES). The TEM data reveal that GO consists of amorphous and crystalline phases. The XPS data show that some carbon atoms have sp(3) orbitals and others have sp(2) orbitals. The ratio of sp(2) to sp(3) bonded carbon atoms decreases as sample preparation times increase. The (13)C solid-state NMR spectra of GO indicate the existence of -OH and -O- groups for which peaks appear at 60 and 70 ppm, respectively. FT-IR results corroborate these findings. The existence of ketone groups is also implied by FT-IR, which is verified by O K-edge XANES and (13)C solid-state NMR. We propose a new model for GO based on the results; -O-, -OH, and -C=O groups are on the surface.

Rapid neutron-diffraction data collection for hydrogen-bonding studies: application of the Laue diffractometer (LADI) to the case study zinc (tris)thiourea sulfate.

The successful application of the newly developed image-plate neutron Laue diffractometer (LADI) at the Institut Laue-Langevin (ILL), Grenoble, France, for rapid hydrogen-bonding characterization is reported. The case study concerns the promising non-linear optical material zinc (tris)thiourea sulfate (ZTS), which contains 30 atoms in the asymmetric unit and crystallizes in the orthorhombic space group, Pca2(1), a = 11.0616 (9), b = 7.7264 (6), c = 15.558 (1) A [T = 100.0 (1) K]. The results from a 12 h data collection from ZTS on LADI are compared with those obtained over 135 h using the monochromatic four-circle diffractometer D9 at the same reactor source with a crystal 13 times larger in volume. Both studies reveal the extensive hydrogen bonding and other close non-bonded contacts within the material. As expected, the results from D9 are more precise than those obtained from LADI; however, the bond geometry determined from the two experiments is the same within the larger estimated standard deviations. Furthermore, the conclusions drawn from the two studies separately regarding the nature of all supramolecular features are identical. This illustrates that LADI is eminently suitable for rapid characterization of hydrogen-bonded structures by neutron diffraction, with the gain in speed compared with traditional instrumentation being several orders of magnitude.

Influence of hydrogen bonding on the second harmonic generation effect: neutron diffraction study of 4-nitro-4'-methylbenzylidene aniline.

A neutron diffraction study of the non-linear optical (NLO) material 4-nitro-4'-methylbenzylidene aniline (NMBA) is presented. NMBA exhibits a large macroscopic second-order NLO susceptibility, chi((2)), and this study shows that hydrogen bonding is, in part, responsible for this. No hydrogen bonding was reported in the X-ray study [Ponomarev et al. (1977). Sov. Phys. Crystallogr. 22, 223-225], whereas the present work shows that C-H.X hydrogen bonds (where X = N, O or pi) direct the nature of the three-dimensional lattice. C-H.X (X = N or O) hydrogen bonds are common; however, C-H.pi hydrogen-bond motifs are relatively rare. Such intermolecular interactions help extend the molecular charge transfer into the supramolecular realm, the charge transfer originating as a consequence of the high level of molecular planarity and strong donor-to-acceptor interactions. Molecular planarity, coupled with the favourable nature of the hydrogen bonds, results in parallel stacking of molecules in both the a and c crystallographic directions with extremely close interplanar spacings. Such a combination of influential hydrogen-bonding characteristics accounts, in part, for the large second-order NLO output of the material since the phenomenon is so critically dependent upon the nature of the charge transfer.

Long-term follow-up of stapedectomy in children and adolescents.

Otosclerosis presenting in children and adolescents is uncommon. Typically, otosclerosis presents as a slowly progressive conductive hearing loss in the third to fourth decade. Many well-documented studies have demonstrated excellent long-term hearing results with stapedectomy. Although stapedectomy is highly effective, the rare complications may be devastating. Thirty-one patients, 21 years or younger, underwent 40 stapedectomies for otosclerosis at our institution. The average age at surgery was 16 years, with a range of 7 to 21 years. Postoperative results showed an average improvement in air-bone gap of 22 dB. Clinical and audiologic data were collected over a mean follow-up period of 25 years. There was no statistically significant difference in air-bone gap when comparing the immediate postoperative gap (measured 2 months after stapedectomy) with the last gap recorded (mean, 25 years after stapedectomy). Fifty percent of the ears operated on maintained an air-bone gap within 10 dB at the last follow-up, and an additional 40% maintained a 10- to 20-dB gap. There were no significant relationships between demographic or clinical factors and "success" (gap <= 10 dB) or long-term gap closure. Our data demonstrate that stapedectomy is an effective method for closing the air-bone gap in children and adolescents with otosclerosis, and long-term results parallel those of adults, showing maintenance of excellent gap closure. This review represents the largest population with the longest follow-up in children who underwent stapedectomy for the treatment of otosclerosis.

Long-term results of treatment for glomus jugulare and glomus vagale tumors with radiotherapy.

Since 1954, 39 cases of glomus jugulare or vagale tumor have been treated by the authors with radiotherapy. The initial results with orthovoltage (280 kV) therapy were unpredictable, but 30 patients with 32 tumors treated with megavoltage radiotherapy (Cobalt-60 [60Co] or linear accelerator) have shown either no evidence of recurrence or complications, with one exception, or died of causes unrelated to their glomus tumor. Megavoltage radiotherapy is recommended for primary treatment of all glomus tumors that present with evidence of bone invasion or nerve involvement.

Primary cutaneous neuroendocrine carcinoma (Merkel cell tumor). An adnexal epithelial neoplasm.

We report 18 cases of primary cutaneous neuroendocrine carcinoma (CNEC, Merkel cell tumor) that occurred mainly in the sun-exposed skin of elderly patients as dermal and subcutaneous masses of generally monomorphic cells with foci of pronounced pleomorphism. All 18 cases showed immunoreactivity for neuron-specific enolase (NSE), whereas 16 of them showed immunoreactivity for another neuroendocrine marker, protein gene product 9.5 (PGP 9.5). Positivity for PGP 9.5 was more intense and more sharply localized to tumor cells than the staining for NSE. Immunoreactivity for keratins detected by AE1/AE3 and CAM 5.2 monoclonal antibodies was found in 16 and 15 cases, respectively, with prominent paranuclear globular staining. One case stained positively for S-100 protein; all were negative for leukocyte common antigen (LCA). Typical ultrastructural features of neuroendocrine differentiation were noted in all of 14 tumors examined. Morphological and immunohistochemical similarities between these neoplasms and pulmonary small-cell anaplastic carcinoma, now thought to be of bronchial basal cell origin, suggest that CNEC are also derived from epithelium. In addition, their dermal location suggests that this epithelium is likely to be adnexal rather than epidermal.