Good Timing Matters: The Spatially Fractionated High Dose Rate Boost Should Come First.

Monoplanar microbeam irradiation (MBI) and pencilbeam irradiation (PBI) are two new concepts of high dose rate radiotherapy, combined with spatial dose fractionation at the micrometre range. In a small animal model, we have explored the concept of integrating MBI or PBI as a simultaneously integrated boost (SIB), either at the beginning or at the end of a conventional, low-dose rate schedule of 5x4 Gy broad beam (BB) whole brain radiotherapy (WBRT). MBI was administered as array of 50 µm wide, quasi-parallel microbeams. For PBI, the target was covered with an array of 50 µm × 50 µm pencilbeams. In both techniques, the centre-to-centre distance was 400 µm. To assure that the entire brain received a dose of at least 4 Gy in all irradiated animals, the peak doses were calculated based on the daily BB fraction to approximate the valley dose. The results of our study have shown that the sequence of the BB irradiation fractions and the microbeam SIB is important to limit the risk of acute adverse effects, including epileptic seizures and death. The microbeam SIB should be integrated early rather than late in the irradiation schedule

How to reduce test anxiety and academic procrastination through inquiry of cognitive appraisals: A pilot study investigating the role of academic self-efficacy

Background and Objectives: Test anxiety can impair learning motivation and lead to procrastination. Control-value theory of achievement emotions (Pekrun, 2006) assumes test anxiety to be a result of students’ appraisals of the testing situation and its outcomes. Modification of cognitive appraisals such as low self-efficacy beliefs is thus assumed to reduce test anxiety and subsequent procrastination. In the present study, we tested the effects of an inquiry-based stress reduction (IBSR) intervention on students’ academic self-efficacy, their test anxiety, and subsequent procrastination in the final stages of an academic term. Design: Longitudinal quasi-randomized intervention control trial. Methods: University students identified worry thoughts regarding a specific and frightening testing situation. Intervention participants (n = 40) explored their worry thoughts with the IBSR method. Participants of an active waitlist control group (n = 31) received the intervention after the study was completed. Dependent variables were assessed before and after the intervention as well as at the end of the term. Results: Data-analyses revealed that the IBSR intervention reduced test anxiety as well as subsequent academic procrastination in comparison to the control group. The effect on test anxiety was partly due to an enhancement of self-efficacy. Conclusion: Our findings provide preliminary evidence that IBSR might help individuals to cope with their test anxiety and procrastination

TRANSMISSION OF SIGNALS FROM RATS RECEIVING HIGH DOSES OF MICROBEAM RADIATION TO CAGE MATES: AN INTER-MAMMAL BYSTANDER EFFECT

Inter-animal signaling from irradiated to non-irradiated organisms has been demonstrated for whole body irradiated mice and also for fish. The aim of the current study was to look at radiotherapy style limited exposure to part of the body using doses relevant in preclinical therapy. High dose homogenous field irradiation and the use of irradiation in the microbeam radiation therapy mode at the European Synchrotron Radiation Facility (ESRF) at Grenoble was tested by giving high doses to the right brain hemisphere of the rat. The right and left cerebral hemispheres and the urinary bladder were later removed to determine whether abscopal effects could be produced in the animals and also whether effects occurred in cage mates housed with them. The results show strong bystander signal production in the contra-lateral brain hemisphere and weaker effects in the distant bladder of the irradiated rats. Signal strength was similar or greater in each tissue in the cage mates housed for 48hrs with the irradiated rats. Our results support the hypothesis that proximity to an irradiated animal induces signalling changes in an unirradiated partner. If similar signaling occurs between humans, the results could have implications for caregivers and hospital staff treating radiotherapy patients

Microbeam Irradiation as a Simultaneously Integrated Boost in a Conventional Whole-Brain Radiotherapy Protocol.

Microbeam radiotherapy (MRT), an experimental high-dose rate concept with spatial fractionation at the micrometre range, has shown a high therapeutic potential as well as good preservation of normal tissue function in pre-clinical studies. We investigated the suitability of MRT as a simultaneously integrated boost (SIB) in conventional whole-brain irradiation (WBRT). A 174 Gy MRT SIB was administered with an array of quasi-parallel, 50 µm wide microbeams spaced at a centre-to-centre distance of 400 µm either on the first or last day of a 5 × 4 Gy radiotherapy schedule in healthy adult C57 BL/6J mice and in F98 glioma cell cultures. The animals were observed for signs of intracranial pressure and focal neurologic signs. Colony counts were conducted in F98 glioma cell cultures. No signs of acute adverse effects were observed in any of the irradiated animals within 3 days after the last irradiation fraction. The tumoricidal effect on F98 cell in vitro was higher when the MRT boost was delivered on the first day of the irradiation course, as opposed to the last day. Therefore, the MRT SIB should be integrated into a clinical radiotherapy schedule as early as possible

Serum levels of S100B from jugular bulb as a biomarker of poor prognosis in patients with severe acute brain injury

Aims/background To evaluate the correlation between protein S100B concentrations measured in the jugular bulb as well as at peripheral level and the prognostic usefulness of this marker. Methods A prospective study of all patients admitted to the intensive care unit with acute brain damage was carried out. Peripheral and jugular bulb blood samples were collected upon admission and every 24 h for three days. The endpoints were brain death diagnosis and the Glasgow Outcome Scale score after 6 months. Results A total of 83 patients were included. Jugular protein S100B levels were greater than systemic levels upon admission and also after 24 and 72 h (mean difference > 0). Jugular protein S100B levels showed acceptable precision in predicting brain death both upon admission [AUC 0.67 (95% CI 0.53?0.80)] and after 48 h [AUC 0.73 (95% CI 0.57?0.89)]. Similar results were obtained regarding the capacity of jugular protein S100B levels upon admission to predict an unfavourable outcome (AUC 0.69 (95% CI 0.56?0.79)). The gradient upon admission (jugular-peripheral levels) showed its capacity to predict the development of brain death [AUC 0.74 (95% CI 0.62?0.86)] and together with the Glasgow Coma Scale constituted the independent factors associated with the development of brain death. Conclusion Regional protein S100B determinations are higher than systemic determinations, thus confirming the cerebral origin of protein S100B. The transcranial protein S100B gradient is correlated to the development of brain death.This study has been supported by grants from the Marqués de Valdecilla Foundation - IFIMAV (API 10/02) and the Spanish Ministry of Science - Carlos III Health Institute (PI080058). The protein S100B electrochemoluminescence assay kits were a generous donation from Roche Diagnostics, Mannheim, Germany The authors report no conflicts of interest. The authors alone are responsible for the contents and writing of the paper

Real time observation of mouse fetal skeleton using a high resolution X-ray synchrotron

The X-ray synchrotron is quite different from conventional radiation sources. This technique may expand the capabilities of conventional radiology and be applied in novel manners for special cases. To evaluate the usefulness of X-ray synchrotron radiation systems for real time observations, mouse fetal skeleton development was monitored with a high resolution X-ray synchrotron. A non-monochromatized X-ray synchrotron (white beam, 5C1 beamline) was employed to observe the skeleton of mice under anesthesia at embryonic day (E)12, E14, E15, and E18. At the same time, conventional radiography and mammography were used to compare with X-ray synchrotron. After synchrotron radiation, each mouse was sacrificed and stained with Alizarin red S and Alcian blue to observe bony structures. Synchrotron radiation enabled us to view the mouse fetal skeleton beginning at gestation. Synchrotron radiation systems facilitate real time observations of the fetal skeleton with greater accuracy and magnification compared to mammography and conventional radiography. Our results show that X-ray synchrotron systems can be used to observe the fine structures of internal organs at high magnification

Study of the X-ray radiation interaction with a multislit collimator for the creation of microbeams in radiation therapy

Microbeam radiation therapy (MRT) is a developing radiotherapy, based on the use of beams only a few tens of micrometres wide, generated by synchrotron X-ray sources. The spatial fractionation of the homogeneous beam into an array of microbeams is possible using a multislit collimator (MSC), i.e. a machined metal block with regular apertures. Dosimetry in MRT is challenging and previous works still show differences between calculated and experimental dose profiles of 10-30%, which are not acceptable for a clinical implementation of treatment. The interaction of the X-rays with the MSC may contribute to the observed discrepancies; the present study therefore investigates the dose contribution due to radiation interaction with the MSC inner walls and radiation leakage of the MSC. Dose distributions inside a water-equivalent phantom were evaluated for different field sizes and three typical spectra used for MRT studies at the European Synchrotron Biomedical beamline ID17. Film dosimetry was utilized to determine the contribution of radiation interaction with the MSC inner walls; Monte Carlo simulations were implemented to calculate the radiation leakage contribution. Both factors turned out to be relevant for the dose deposition, especially for small fields. Photons interacting with the MSC walls may bring up to 16% more dose in the valley regions, between the microbeams. Depending on the chosen spectrum, the radiation leakage close to the phantom surface can contribute up to 50% of the valley dose for a 5 mm × 5 mm field. The current study underlines that a detailed characterization of the MSC must be performed systematically and accurate MRT dosimetry protocols must include the contribution of radiation leakage and radiation interaction with the MSC in order to avoid significant errors in the dose evaluation at the micrometric scale