Stabilized Radiation Pressure Acceleration and Neutron Generation in Ultrathin Deuterated Foils.

Premature relativistic transparency of ultrathin, laser-irradiated targets is recognized as an obstacle to achieving a stable radiation pressure acceleration in the "light sail" (LS) mode. Experimental data, corroborated by 2D PIC simulations, show that a few-nm thick overcoat surface layer of high Z material significantly improves ion bunching at high energies during the acceleration. This is diagnosed by simultaneous ion and neutron spectroscopy following irradiation of deuterated plastic targets. In particular, copious and directional neutron production (significantly larger than for other in-target schemes) arises, under optimal parameters, as a signature of plasma layer integrity during the acceleration.

Absolute calibration of Fujifilm BAS-TR image plate response to laser driven protons up to 40 MeV.

Image plates (IPs) are a popular detector in the field of laser driven ion acceleration, owing to their high dynamic range and reusability. An absolute calibration of these detectors to laser-driven protons in the routinely produced tens of MeV energy range is, therefore, essential. In this paper, the response of Fujifilm BAS-TR IPs to 1-40 MeV protons is calibrated by employing the detectors in high resolution Thomson parabola spectrometers in conjunction with a CR-39 nuclear track detector to determine absolute proton numbers. While CR-39 was placed in front of the image plate for lower energy protons, it was placed behind the image plate for energies above 10 MeV using suitable metal filters sandwiched between the image plate and CR-39 to select specific energies. The measured response agrees well with previously reported calibrations as well as standard models of IP response, providing, for the first time, an absolute calibration over a large range of proton energies of relevance to current experiments.

Calibration of BAS-TR image plate response to GeV gold ions.

The response of the BAS-TR image plate (IP) was absolutely calibrated using a CR-39 track detector for high linear energy transfer Au ions up to ∼1.6 GeV (8.2 MeV/nucleon), accelerated by high-power lasers. The calibration was carried out by employing a high-resolution Thomson parabola spectrometer, which allowed resolving Au ions with closely spaced ionization states up to 58+. A response function was obtained by fitting the photo-stimulated luminescence per Au ion for different ion energies, which is broadly in agreement with that expected from ion stopping in the active layer of the IP. This calibration would allow quantifying the ion energy spectra for high energy Au ions, which is important for further investigation of the laser-based acceleration of heavy ion beams.

Development and Validation of a Short Version of the Metric for the Observation of Decision-Making in Multidisciplinary Tumor Boards: MODe-Lite.

BACKGROUND: Evidence-based tools are necessary for scientifically improving the way MTBs work. Such tools are available but can be difficult to use. This study aimed to develop a robust observational assessment tool for use on cancer multidisciplinary tumor boards (MTBs) by health care professionals in everyday practice. METHODS: A retrospective cross-sectional observational study was conducted in the United Kingdom from September 2015 to July 2016. Three tumor boards from three teaching hospitals were recruited, with 44 members overall. Six weekly meetings involving 146 consecutive cases were video-recorded and scored using the validated MODe tool. Data were subjected to reliability and validity analysis in the current study to develop a shorter version of the MODe. RESULTS: Phase 1, a reduction of the original items in the MODe, was achieved through two focus group meetings with expert assessors based on previous research. The 12 original items were reduced to 6 domains, receiving full agreement by the assessors. In phase 2, the six domains were subjected to item reliability, convergent validation, and internal consistency testing against the MODe-Lite global score, the MODe global score, and the items of the MODe. Significant positive correlations were evident across all domains (p < 0.01), indicating good reliability and validity. In phase 3, feasibility and high inter-assessor reliability were achieved by two clinical assessors. Six domains measuring clinical input, holistic input, clinical collaboration, pathology, radiology, and management plan were integrated into MODe-Lite. CONCLUSIONS: As an evidence-based tool for health care professionals in everyday practice, MODe-Lite gives cancer MTBs insight into the way they work and facilitates improvements in practice.

Enhanced spatial resolution of Eljen-204 plastic scintillators for use in rep-rated proton diagnostics.

A pixelated scintillator has been designed, fabricated, and tested using a laser-accelerated proton source for use in proton diagnostics at rep-rated laser facilities. The work presented here demonstrates the enhanced spatial resolution of thin, organic scintillators through a novel pixelation technique. Experimental measurements using laser-generated protons incident onto 130 µm-thick scintillators indicate a >20% reduction in the scintillator point spread function (PSF) for the detectors tested. The best performing pixelated detector reduced the ∼200 µm PSF of the stock material to ∼150 µm. The fabrication technique may be tailored to reduce the pixel size and achieve higher spatial resolutions.

Analysing Breast Cancer Multidisciplinary Patient Management: A Prospective Observational Evaluation of Team Clinical Decision-Making.

BACKGROUND: Multidisciplinary team (MDT)-driven cancer care is a mandatory UK national policy, widely used globally. However, few studies have examined how MDT members make decisions as a team. We report a single-centre prospective study on team working within breast cancer MDT. METHODS: This was a prospective observational study of 10 breast MDT meetings (MDM). Trained clinical observer scored quality of presented information and disciplinary contribution to case reviews in real time, using a validated tool, namely Metric for the Observation of Decision-Making. Data were analysed to evaluate quality of team working. RESULTS: Ten MDMs were observed (N = 346 patients). An average of 42 patients were discussed per MDM (range: 29-51) with an average 3 min 20 s (range: 31 s-9 min) dedicated to each patient. Management decision was made in 99% of cases. In terms of contribution to case reviews, breast care nurses scored significantly (p < 0.05) lower (M = 1.79, SD = 0.12) compared to other team members (e.g. surgeons, M = 4.65; oncologists, M = 3.07; pathologists, M = 4.51; radiologists, M = 3.21). Information on patient psychosocial aspects (M = 1.69, SD = 0.68), comorbidities (M = 1.36, SD = 0.39) and views on treatment options (M = 1.47, SD = 0.34) was also significantly (p < 0.05) less well represented compared to radiology (M = 3.62, SD = 0.77), pathology (M = 4.42, SD = 0.49) and patient history (M = 3.91, SD = 0.48). CONCLUSION: MDT evaluation via direct observation in a meeting is feasible and reliable. We found consistent levels of quality of information coverage and contribution within the team, but certain aspects could be improved. Contribution to patient review resides predominantly with surgeons, while presented patient information is largely of biomedical nature. These findings can be fed to cancer MDTs to identify potential interventions for improvement.

Time-resolved measurements of fast electron recirculation for relativistically intense femtosecond scale laser-plasma interactions.

A key issue in realising the development of a number of applications of high-intensity lasers is the dynamics of the fast electrons produced and how to diagnose them. We report on measurements of fast electron transport in aluminium targets in the ultra-intense, short-pulse (<50 fs) regime using a high resolution temporally and spatially resolved optical probe. The measurements show a rapidly (≈0.5c) expanding region of Ohmic heating at the rear of the target, driven by lateral transport of the fast electron population inside the target. Simulations demonstrate that a broad angular distribution of fast electrons on the order of 60° is required, in conjunction with extensive recirculation of the electron population, in order to drive such lateral transport. These results provide fundamental new insight into fast electron dynamics driven by ultra-short laser pulses, which is an important regime for the development of laser-based radiation and particle sources.

Near-100 MeV protons via a laser-driven transparency-enhanced hybrid acceleration scheme.

The range of potential applications of compact laser-plasma ion sources motivates the development of new acceleration schemes to increase achievable ion energies and conversion efficiencies. Whilst the evolving nature of laser-plasma interactions can limit the effectiveness of individual acceleration mechanisms, it can also enable the development of hybrid schemes, allowing additional degrees of control on the properties of the resulting ion beam. Here we report on an experimental demonstration of efficient proton acceleration to energies exceeding 94 MeV via a hybrid scheme of radiation pressure-sheath acceleration in an ultrathin foil irradiated by a linearly polarised laser pulse. This occurs via a double-peaked electrostatic field structure, which, at an optimum foil thickness, is significantly enhanced by relativistic transparency and an associated jet of super-thermal electrons. The range of parameters over which this hybrid scenario occurs is discussed and implications for ion acceleration driven by next-generation, multi-petawatt laser facilities are explored.

A computational model of ureteral peristalsis and an investigation into ureteral reflux.

The aim of this study is to create a computational model of the human ureteral system that accurately replicates the peristaltic movement of the ureter for a variety of physiological and pathological functions. The objectives of this research are met using our in-house fluid-structural dynamics code (CgLes-Y code). A realistic peristaltic motion of the ureter is modelled using a novel piecewise linear force model. The urodynamic responses are investigated under two conditions of a healthy and a depressed contraction force. A ureteral pressure during the contraction shows a very good agreement with corresponding clinical data. The results also show a dependency of the wall shear stresses on the contraction velocity and it confirms the presence of a high shear stress at the proximal part of the ureter. Additionally, it is shown that an inefficient lumen contraction can increase the possibility of a continuous reflux during the propagation of peristalsis.

Micron-scale mapping of megagauss magnetic fields using optical polarimetry to probe hot electron transport in petawatt-class laser-solid interactions.

The transport of hot, relativistic electrons produced by the interaction of an intense petawatt laser pulse with a solid has garnered interest due to its potential application in the development of innovative x-ray sources and ion-acceleration schemes. We report on spatially and temporally resolved measurements of megagauss magnetic fields at the rear of a 50-µm thick plastic target, irradiated by a multi-picosecond petawatt laser pulse at an incident intensity of ~1020 W/cm2. The pump-probe polarimetric measurements with micron-scale spatial resolution reveal the dynamics of the magnetic fields generated by the hot electron distribution at the target rear. An annular magnetic field profile was observed ~5 ps after the interaction, indicating a relatively smooth hot electron distribution at the rear-side of the plastic target. This is contrary to previous time-integrated measurements, which infer that such targets will produce highly structured hot electron transport. We measured large-scale filamentation of the hot electron distribution at the target rear only at later time-scales of ~10 ps, resulting in a commensurate large-scale filamentation of the magnetic field profile. Three-dimensional hybrid simulations corroborate our experimental observations and demonstrate a beam-like hot electron transport at initial time-scales that may be attributed to the local resistivity profile at the target rear.

Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care.

An accurate diagnosis is an integral component of patient care for children with rare genetic disease. Recent advances in sequencing, in particular whole-exome sequencing (WES), are identifying the genetic basis of disease for 25-40% of patients. The diagnostic rate is probably influenced by when in the diagnostic process WES is used. The Finding Of Rare Disease GEnes (FORGE) Canada project was a nation-wide effort to identify mutations for childhood-onset disorders using WES. Most children enrolled in the FORGE project were toward the end of the diagnostic odyssey. The two primary outcomes of FORGE were novel gene discovery and the identification of mutations in genes known to cause disease. In the latter instance, WES identified mutations in known disease genes for 105 of 362 families studied (29%), thereby informing the impact of WES in the setting of the diagnostic odyssey. Our analysis of this dataset showed that these known disease genes were not identified prior to WES enrollment for two key reasons: genetic heterogeneity associated with a clinical diagnosis and atypical presentation of known, clinically recognized diseases. What is becoming increasingly clear is that WES will be paradigm altering for patients and families with rare genetic diseases.

The use of urological hospital services by nonagenarians.

INTRODUCTION: The super-elderly population is a small but expanding group of patients who will pose a significant challenge to future healthcare resources. A snapshot audit was completed of all emergency and elective urological nonagenarian activity in a UK general hospital, including surgical outcomes in this group of patients. METHODS: Prospective and retrospective databases and clinical records were examined to identify all patients aged 90-99 years who had patient episodes between January 2006 and August 2012. Patient outcomes were compared with those for a similar cohort of 80-89-year-olds during the same time period. RESULTS: A total of 653 nonagenarian patient episodes were identified (including 138 emergency admissions, 25 emergency surgical procedures, 71 elective surgical procedures, 173 local anaesthetic procedures and 270 outpatient visits). The in-hospital mortality rate for emergency admissions was 10%. The mean length of hospital stay was significantly longer for nonagenarians than for octogenarians (14.4 vs 6.5 days, p<0.00001). The postoperative mortality rate following emergency and elective surgery was 16% and 1% for nonagenarians and octogenarians respectively. CONCLUSIONS: Nonagenarian patients often have complex medical co-morbidities and challenging social circumstances that contribute to delayed recovery from acute illness and surgery as well as long periods of hospitalisation. Adopting a multidisciplinary approach with formal input from specialist geriatric surgical services may improve patient outcomes and allow patients to be discharged to their former places of residence.

Characterisation of deuterium spectra from laser driven multi-species sources by employing differentially filtered image plate detectors in Thomson spectrometers.

A novel method for characterising the full spectrum of deuteron ions emitted by laser driven multi-species ion sources is discussed. The procedure is based on using differential filtering over the detector of a Thompson parabola ion spectrometer, which enables discrimination of deuterium ions from heavier ion species with the same charge-to-mass ratio (such as C(6+), O(8+), etc.). Commonly used Fuji Image plates were used as detectors in the spectrometer, whose absolute response to deuterium ions over a wide range of energies was calibrated by using slotted CR-39 nuclear track detectors. A typical deuterium ion spectrum diagnosed in a recent experimental campaign is presented, which was produced from a thin deuterated plastic foil target irradiated by a high power laser.

Modified Thomson spectrometer design for high energy, multi-species ion sources.

A modification to the standard Thomson parabola spectrometer is discussed, which is designed to measure high energy (tens of MeV/nucleon), broad bandwidth spectra of multi-species ions accelerated by intense laser plasma interactions. It is proposed to implement a pair of extended, trapezoidal shaped electric plates, which will not only resolve ion traces at high energies, but will also retain the lower energy part of the spectrum. While a longer (along the axis of the undeflected ion beam direction) electric plate design provides effective charge state separation at the high energy end of the spectrum, the proposed new trapezoidal shape will enable the low energy ions to reach the detector, which would have been clipped or blocked by simply extending the rectangular plates to enhance the electrostatic deflection.

Instrumentation for diagnostics and control of laser-accelerated proton (ion) beams.

Suitable instrumentation for laser-accelerated proton (ion) beams is critical for development of integrated, laser-driven ion accelerator systems. Instrumentation aimed at beam diagnostics and control must be applied to the driving laser pulse, the laser-plasma that forms at the target and the emergent proton (ion) bunch in a correlated way to develop these novel accelerators. This report is a brief overview of established diagnostic techniques and new developments based on material presented at the first workshop on 'Instrumentation for Diagnostics and Control of Laser-accelerated Proton (Ion) Beams' in Abingdon, UK. It includes radiochromic film (RCF), image plates (IP), micro-channel plates (MCP), Thomson spectrometers, prompt inline scintillators, time and space-resolved interferometry (TASRI) and nuclear activation schemes. Repetition-rated instrumentation requirements for target metrology are also addressed.

Novel cutaneous effects of combination chemotherapy with BRAF and MEK inhibitors: a report of two cases.

The discovery that some melanoma tumours harbour mutations in the BRAF gene (e.g. V600E) and the subsequent development of specific BRAF inhibitors have greatly improved the treatment of metastatic melanoma. Resistance of tumour cells to BRAF inhibitors is reduced by the addition of an MEK inhibitor; both BRAF and MEK inhibitors have been reported to produce a variety of dermatological toxic effects. Benign naevi often harbour BRAF mutations but few reports exist that document the response of naevus cells to BRAF inhibition. We report sarcoidal-type granulomatous inflammation in two patients with metastatic melanoma undergoing treatment with combination BRAF and MEK inhibitor therapy. This inflammation manifested in one patient as a nonspecific papular eruption; in the other, in association with clinical regression of multiple benign-appearing naevi during the course of therapy. The significance of sarcoidal-type inflammation occurring during treatment of metastatic melanoma with a combination of BRAF and MEK inhibitors is unclear. Its association with the clinical regression of benign-appearing naevi suggests a possible exaggerated inflammatory response to degenerating naevus cells in these lesions.

Multidisciplinary cancer team meeting structure and treatment decisions: a prospective correlational study.

BACKGROUND: Anecdotally, organizational factors appear to have an effect on the quality of decision-making in the multidisciplinary team (MDT) meeting. We assess the effect of the number of team-members present, number and order of cases, and the timing of meetings on the process of decision-making in MDT meetings. METHODS: Between December 2009 and January 2010, data were prospectively collected on treatment decisions, meeting characteristics, quality of information, and teamworking for all cases discussed at a London-based MDT meeting. Variables measured using a validated assessment tool (MDT MODe) and correlational analyses were performed. RESULTS: Treatment decisions were reached in 254 of 298 (85%) cases. Cases toward the end of meetings were associated with lower rates of decision-making, information quality, and teamworking (r = -0.15 to -0.37). Increased number of cases per meeting and team members in attendance were associated with better information and teamworking (r = 0.29-0.43). More time per case was associated with improved teamworking (r = 0.16). A positive correlation was obtained between ability to reach decisions and improved information and teamworking (r = 0.36-0.54; all P ≤ 0.001). CONCLUSIONS: Organizational factors related to the structure of the MDT meeting are associated with variation in the likelihood of reaching a treatment decision. Further research is required to establish causation and to modify such factors in order to improve the quality of cancer care.