Laser generation of proton beams for the production of short-lived positron emitting radioisotopes

Protons of energies up to 37 MeV have been generated when ultra-intense lasers (up to 10(20) W cm(-2)) interact with hydrogen containing solid targets. These protons can be used to induce nuclear reactions in secondary targets to produce P-emitting nuclei of relevance to the nuclear medicine community, namely C-11 and N-13 via (p, n) and (p, alpha) reactions. Activities of the order of 200 kBq have been measured from a single laser pulse interacting with a thin solid target. The possibility of using ultra-intense lasers to produce commercial amounts of short-lived positron emitting sources for positron emission tomography (PET) is discussed. (C) 2001 Elsevier Science B.V. All rights reserved.

Production of radioactive nuclides by energetic protons generated from intense laser-plasma interactions

Nuclear activation has been observed in materials exposed to the ablated plasma generated from high intensity laser-solid interactions (at focused intensities up to 2x10(19) W/cm(2)) and is produced by protons having energies up to 30 MeV. The energy spectrum of the protons is determined from these activation measurements and is found to be consistent with other ion diagnostics. The possible development of this technique for

Hospital antibiotic use and its relationship to age-adjusted comorbidity and alcohol-based hand rub consumption

SUMMARY The objective of this study was to evaluate the effect of age-adjusted comorbidity and alcohol-based hand rub on monthly hospital antibiotic usage, retrospectively. A multivariate autoregressive integrated moving average (ARIMA) model was built to relate the monthly use of all antibiotics grouped together with age-adjusted comorbidity and alcohol-based hand rub over a 5-year period (April 2005-March 2010). The results showed that monthly antibiotic use was positively related to the age-adjusted comorbidity index (concomitant effect, coefficient 1·103, P = 0·0002), and negatively related to the use of alcohol-based hand rub (2-month delay, coefficient -0·069, P = 0·0533). Alcohol-based hand rub is considered a modifiable factor and as such can be identified as a target for quality improvement programmes. Time-series analysis may provide a suitable methodology for identifying possible predictive variables that explain antibiotic use in healthcare settings. Future research should examine the relationship between infection control practices and antibiotic use, identify other infection control predictive factors for hospital antibiotic use, and evaluate the impact of enhancing different infection control practices on antibiotic use in a healthcare setting.

Mechanical characterization of the varian Exact-arm and R-arm support systems for eight aS500 electronic portal imaging devices

The aim of this study is to compare the positioning accuracy at different gantry angles of two electronic portal imaging devices (EPIDs) support arm systems by using EPID difference images as a measure for displacement. This work presents a comparison of the mechanical performance of eight Varian aS500 (Varian Medical Systems, Palo Alto, CA) EPIDs, mounted using either the Varian Exact-arm or R-arm.

Optimization of image quality and dose for Varian aS500 electronic portal imaging devices (EPIDs)

This study was carried out to investigate whether the electronic portal imaging (EPI) acquisition process could be optimized, and as a result tolerance and action levels be set for the PIPSPro QC-3V phantom image quality assessment. The aim of the optimization process was to reduce the dose delivered to the patient while maintaining a clinically acceptable image quality. This is of interest when images are acquired in addition to the planned patient treatment, rather than images being acquired using the treatment field during a patient's treatment. A series of phantoms were used to assess image quality for different acquisition settings relative to the baseline values obtained following acceptance testing. Eight Varian aS500 EPID systems on four matched Varian 600C/D linacs and four matched Varian 2100C/D linacs were compared for consistency of performance and images were acquired at the four main orthogonal gantry angles. Images were acquired using a 6 MV beam operating at 100 MU min(-1) and the low-dose acquisition mode. Doses used in the comparison were measured using a Farmer ionization chamber placed at d(max) in solid water. The results demonstrated that the number of reset frames did not have any influence on the image contrast, but the number of frame averages did. The expected increase in noise with corresponding decrease in contrast was also observed when reducing the number of frame averages. The optimal settings for the low-dose acquisition mode with respect to image quality and dose were found to be one reset frame and three frame averages. All patients at the Northern Ireland Cancer Centre are now imaged using one reset frame and three frame averages in the 6 MV 100 MU min(-1) low-dose acquisition mode. Routine EPID QC contrast tolerance (+/-10) and action (+/-20) levels using the PIPSPro phantom based around expected values of 190 (Varian 600C/D) and 225 (Varian 2100C/D) have been introduced. The dose at dmax from electronic portal imaging has been reduced by approximately 28%, and while the image quality has been reduced, the images produced are still clinically acceptable.

Octavius 4D characterization for flattened and flattening filter free rotational deliveries

Purpose: In this study the Octavius detector 729 ionization chamber (IC) array with the Octavius 4D phantom was characterized for flattening filter (FF) and flattening filter free (FFF) static and rotational beams. The device was assessed for verification with FF and FFF RapidArc treatment plans.

Methods: The response of the detectors to field size, dose linearity, and dose rate were assessed for 6 MV FF beams and also 6 and 10 MV FFF beams. Dosimetric and mechanical accuracy of the detector array within the Octavius 4D rotational phantom was evaluated against measurements made using semiflex and pinpoint ionization chambers, and radiochromic film. Verification FF and FFF RapidArc plans were assessed using a gamma function with 3%/3 mm tolerances and 2%/2 mm tolerances and further analysis of these plans was undertaken using film and a second detector array with higher spatial resolution.

Results: A warm-up dose of >6 Gy was required for detector stability. Dose-rate measurements were stable across a range from 0.26 to 15 Gy/min and dose response was linear, although the device overestimated small doses compared with pinpoint ionization chamber measurements. Output factors agreed with ionization chamber measurements to within 0.6% for square fields of side between 3 and 25 cm and within 1.2% for 2 x 2 cm(2) fields. The Octavius 4D phantom was found to be consistent with measurements made with radiochromic film, where the gantry angle was found to be within 0.4. of that expected during rotational deliveries. RapidArc FF and FFF beams were found to have an accuracy of >97.9% and >90% of pixels passing 3%/3 mm and 2%/2 mm, respectively. Detector spatial resolution was observed to be a factor in determining the accurate delivery of each plan, particularly at steep dose gradients. This was confirmed using data from a second detector array with higher spatial resolution and with radiochromic film.

Conclusions: The Octavius 4D phantom with associated Octavius detector 729 ionization chamber array is a dosimetrically and mechanically stable device for pretreatment verification of FF and FFF RapidArc treatments. Further improvements may be possible through use of a detector array with higher spatial resolution (detector size and/or detector spacing). (C) 2013 American Association of Physicists in Medicine.

Heparin induced thrombocytopenia causing life-threatening postoperative haemorrhage

Heparin is ubiquitously employed in surgery in the prevention and treatment of thromboembolic disorders. A small but significant number of patients receiving heparin develop thrombocytopenia and are at risk of both serious thromboembolic disease and haemorrhage. A case is reported where a young woman developed life-threatening postoperative haemorrhage associated with heparin induced thrombocytopenia (HIT).

The VLT-FLAMES Tarantula Survey XI. A census of the hot luminous stars and their feedback in 30 Doradus

Context. The VLT-FLAMES Tarantula Survey has an extensive view of the copious number of massive stars in the 30 Doradus (30 Dor) star forming region of the Large Magellanic Cloud. These stars play a crucial role in our understanding of the stellar feedback in more distant, unresolved star forming regions. Aims. The first comprehensive census of hot luminous stars in 30 Dor is compiled within a 10 arcmin (150 pc) radius of its central cluster, R136. We investigate the stellar content and spectroscopic completeness of the early type stars. Estimates were made for both the integrated ionising luminosity and stellar wind luminosity. These values were used to re-assess the star formation rate (SFR) of the region and determine the ionising photon escape fraction. Methods. Stars were selected photometrically and combined with the latest spectral classifications. Spectral types were estimated for stars lacking spectroscopy and corrections were made for binary systems, where possible. Stellar calibrations were applied to obtain their physical parameters and wind properties. Their integrated properties were then compared to global observations from ultraviolet (UV) to far-infrared (FIR) imaging as well as the population synthesis code, Starburst99. Results. Our census identified 1145 candidate hot luminous stars within 150 pc of R136 of which >700 were considered to be genuine early type stars and contribute to feedback. We assess the survey to be spectroscopically complete to 85% in the outer regions (>5 pc) but only 35% complete in the region of the R136 cluster, giving a total of 500 hot luminous stars in the census which had spectroscopy. Only 31 were found to be Wolf-Rayet (W-R) or Of/WN stars, but their contribution to the integrated ionising luminosity and wind luminosity was ~ 40% and ~ 50%, respectively. Similarly, stars with M > 100 M (mostly H-rich WN stars) also showed high contributions to the global feedback, ~ 25% in both cases. Such massive stars are not accounted for by the current Starburst99 code, which was found to underestimate the integrated ionising luminosity of R136 by a factor ~ 2 and the wind luminosity by a factor ~ 9. The census inferred a SFR for 30 Dor of 0.073 ± 0.04 M yr . This was generally higher than that obtained from some popular SFR calibrations but still showed good consistency with the far-UV luminosity tracer as well as the combined Hα and mid-infrared tracer, but only after correcting for Hα extinction. The global ionising output was also found to exceed that measured from the associated gas and dust, suggesting that ~6 % of the ionising photons escape the region. Conclusions. When studying the most luminous star forming regions, it is essential to include their most massive stars if one is to determine a reliable energy budget. Photon leakage becomes more likely after including their large contributions to the ionising output. If 30 Dor is typical of other massive star forming regions, estimates of the SFR will be underpredicted if this escape fraction is not accounted for.

A feasibility study testing four hypotheses with phase II outcomes in advanced colorectal cancer (MRC FOCUS3): a model for randomised controlled trials in the era of personalised medicine?

Background: Molecular characteristics of cancer vary between individuals. In future, most trials will require assessment of biomarkers to allocate patients into enriched populations in which targeted therapies are more likely to be effective. The MRC FOCUS3 trial is a feasibility study to assess key elements in the planning of such studies.

Patients and methods: Patients with advanced colorectal cancer were registered from 24 centres between February 2010 and April 2011. With their consent, patients' tumour samples were analysed for KRAS/BRAF oncogene mutation status and topoisomerase 1 (topo-1) immunohistochemistry. Patients were then classified into one of four molecular strata; within each strata patients were randomised to one of two hypothesis-driven experimental therapies or a common control arm (FOLFIRI chemotherapy). A 4-stage suite of patient information sheets (PISs) was developed to avoid patient overload.

Results: A total of 332 patients were registered, 244 randomised. Among randomised patients, biomarker results were provided within 10 working days (w.d.) in 71%, 15 w.d. in 91% and 20 w.d. in 99%. DNA mutation analysis was 100% concordant between two laboratories. Over 90% of participants reported excellent understanding of all aspects of the trial. In this randomised phase II setting, omission of irinotecan in the low topo-1 group was associated with increased response rate and addition of cetuximab in the KRAS, BRAF wild-type cohort was associated with longer progression-free survival.

Conclusions: Patient samples can be collected and analysed within workable time frames and with reproducible mutation results. Complex multi-arm designs are acceptable to patients with good PIS. Randomisation within each cohort provides outcome data that can inform clinical practice.

Monitoring daily MLC positional errors using trajectory log files and EPID measurements for IMRT and VMAT deliveries

This work investigated the differences between multileaf collimator (MLC) positioning accuracy determined using either log files or electronic portal imaging devices (EPID) and then assessed the possibility of reducing patient specific quality control (QC) via phantom-less methodologies. In-house software was developed, and validated, to track MLC positional accuracy with the rotational and static gantry picket fence tests using an integrated electronic portal image. This software was used to monitor MLC daily performance over a 1 year period for two Varian TrueBeam linear accelerators, with the results directly compared with MLC positions determined using leaf trajectory log files. This software was validated by introducing known shifts and collimator errors. Skewness of the MLCs was found to be 0.03 ± 0.06° (mean ±1 standard deviation (SD)) and was dependent on whether the collimator was rotated manually or automatically. Trajectory log files, analysed using in-house software, showed average MLC positioning errors with a magnitude of 0.004 ± 0.003 mm (rotational) and 0.004 ± 0.011 mm (static) across two TrueBeam units over 1 year (mean ±1 SD). These ranges, as indicated by the SD, were lower than the related average MLC positioning errors of 0.000 ± 0.025 mm (rotational) and 0.000 ± 0.039 mm (static) that were obtained using the in-house EPID based software. The range of EPID measured MLC positional errors was larger due to the inherent uncertainties of the procedure. Over the duration of the study, multiple MLC positional errors were detected using the EPID based software but these same errors were not detected using the trajectory log files. This work shows the importance of increasing linac specific QC when phantom-less methodologies, such as the use of log files, are used to reduce patient specific QC. Tolerances of 0.25 mm have been created for the MLC positional errors using the EPID-based automated picket fence test. The software allows diagnosis of any specific leaf that needs repair and gives an indication as to the course of action that is required.

Subcutaneous inflammation mimicking metastatic malignancy induced by injection of mistletoe extract

We describe the histological features of subcutaneous inflammation induced by mistletoe, a popular Christmas decoration, when used as an anticancer complementary therapy. We also outline the use of extract of mistletoe in this context.

Element-specific depth profile of magnetism and stoichiometry at the La0.67Sr0.33MnO3/BiFeO3 interface

Depth-sensitive magnetic, structural and chemical characterization is important in the understanding and optimization of novel physical phenomena emerging at interfaces of transition metal oxide heterostructures. In a simultaneous approach we have used polarized neutron and resonant X-ray reflectometry to determine the magnetic profile across atomically sharp interfaces of ferromagnetic La0.67Sr0.33MnO3 / multiferroic BiFeO3 bi-layers with sub-nanometer resolution. In particular, the X-ray resonant magnetic reflectivity measurements at the Fe and Mn resonance edges allowed us to determine the element specific depth profile of the ferromagnetic moments in both the La0.67Sr0.33MnO3 and BiFeO3 layers. Our measurements indicate a magnetically diluted interface layer within the La0.67Sr0.33MnO3 layer, in contrast to previous observations on inversely deposited layers. Additional resonant X-ray reflection measurements indicate a region of an altered Mn- and O-content at the interface, with a thickness matching that of the magnetic diluted layer, as origin of the reduction of the magnetic moment.