Improved FBX chemical dosimeter system with enhanced radiochemical yield for reference dosimetry in radiobiology and radiotherapy research

Radiation dosimetry plays important role in the reproducibility of radiobiology experiments, in the replicability of results, as well as in the successful and safe use of radiotherapy procedures. The consistency and accuracy of the applied dosimetry methods pre-define the outcomes of these applications. This paper presents a version of the well-known ferrous sulphate – benzoic acid – xylenol orange (FBX) chemical dosimeter with improved sensitivity, accuracy and precision. Sensitivity is increased due to a slight modification in composition and the preparation procedures. We use stock solutions for the preparation of the dosimeter solution, which consists of 1 mM ferrous sulphate and 16 mM benzoic acid with 0.25 mM xylenol orange added post-irradiation. The nonlinear response to the absorbed dose of this system is eliminated by the increased ferrous sulphate concentration, permitting the calculation of the absorbed dose by a linear relationship between the absorbed dose and the optical absorbance of the solution. The measured chemical yield of our dosimeter is 9.08⋅10−6mol/J for 6 MV photon beams and 6.42⋅10−6mol/J for 250 kVp x-rays. This is a 24% enhancement over the original FBX solution, which permits a finer dose resolution. The accuracy and precision of our method is assured by a well-designed and consistently used practice. A custom designed multipurpose PMMA slab phantom was used for irradiation in reference conditions. This phantom can be used for irradiation in reference conditions of dosimetric solutions, dosimetric films and chemical or biological samples. The combined standard uncertainty of this system is 1.12%, which can be improved by using an appropriate temperature correction factor. Furthermore, a working protocol has been established which allows dosimetry measurements using less than 1 mL dosimetric solutions

An evaluation of the various aspects of the progress in clinical applications of laser driven ionizing radiation

There has been a vast development of laser-driven particle acceleration (LDPA) using high power lasers. This has initiated by the radiation oncology community to use the dose distribution and biological advantages of proton/heavy ion therapy in cancer treatment with a much greater accessibility than currently possible with cyclotron/synchrotron acceleration. Up to now, preclinical experiments have only been performed at a few LDPA facilities; technical solutions for clinical LDPA have been theoretically developed but there is still a long way to go for the clinical introduction of LDPA. Therefore, to explore the further potential bio-medical advantages of LDPA has pronounced importance. The main characteristics of LDPA are the ultra-high beam intensity, the flexibility in beam size reduction and the potential particle and energy selection whilst conventional accelerators generate single particle, quasi mono-energetic beams. There is a growing number of studies on the potential advantages and applications of Energy Modulated X-ray Radiotherapy, Modulated Electron Radiotherapy and Very High Energy Electron (VHEE) delivery system. Furthermore, the ultra-high space and/or time resolution of super-intense beams are under intensive investigation at synchrotrons (microbeam radiation and very high dose rate (> 40 Gy/s) electron accelerator flash irradiation) with growing evidence of significant improvement of the therapeutic index. Boron Neutron Capture Therapy (BNCT) is an advanced cell targeted binary treatment modality. Because of the high linear energy transfer (LET) of the two particles (7Li and 4He) released by 10BNC reaction, all of the energy is deposited inside the tumour cells, killing them with high probability, while the neighbouring cells are not damaged. The limited availability of appropriate neutron sources, prevent the more extensive exploration of clinical benefit of BNCT. Another boron-based novel binary approach is the 11B-Proton Fusion, which result in the release of three high LET alpha particles. These promising, innovative approaches for cancer therapy present huge challenges for dose calculation, dosimetry and for investigation of the biological effects. The planned LDPA (photons, VHEE, protons, carbon ions) at ELI facilities has the unique property of ultra-high dose rate (> Gy/s-10), short pulses, and at ELI-ALPS high repetition rate, have the potential to develop and establish encouraging novel methods working towards compact hospital-based clinical applications. © 2017 IOP Publishing Ltd and Sissa Medialab srl

Automatic Segmentation and Quantitative Analysis of Irradiated Zebrafish Embryos

Radiotherapy is one of the most common methods to treat different cancer cells in clinical application despite having harmful effects on healthy tissues. Radiobiological experiments are very important to determine the irradiation-caused acute and chronic effects to define the exact consequences of different irradiation sources. Photon irradiation has been used on zebrafish embryos, a very new in vivo and appropriate model system in radiobiology. After irradiation, dose-dependent morphological changes were observable in the embryos. These morphological deteriorations were measured manually by biologist researchers during three weeks, which was an extremely time demanding process (15 minutes per image). The aim of this project was to automate this evaluating process, to save time for researchers and to keep the consistence and accuracy of the evaluation. Hence, an algorithm was developed and used to detect the abnormal development of zebrafish embryos

LEISHMANIA BRAZILIENSIS : Cytotoxic, cytostatic and chemotactic effects of poly-lysine-Methotrexate-conjugates

Chemotactic responses play a significant role duringLeishmaniadifferentiation, as well as in the course of parasite–host–cell interaction, a process that precedes a successful infection. The present study uses the modified ‘‘two-chamber capillary assay’’ to quantitatively evaluate the chemotactic properties and the toxic activities of methotrexate containing branched chain polymeric polypeptide conjugates in Leish-mania. Our results demonstrate that this methodology quantitatively determines the taxis of Leishmania towards/against gradients of compounds. They also demonstrate that chemotaxis produced by the poly-peptide–methotrexate conjugates depends on specific chemical characteristics. For example, the N-ter-minal amino acid (Ser or Glu) location at the branch significantly influences the elicited chemotaxis. Furthermore, the use of different attachment sites in the methotrexate conjugates (a-orc-carboxylic groups) affect their chemotactic activity. Specific cytotoxic activities and cytostatic effects of the conju-gates on parasites and on murine and human cells of the macrophage/monocyte system respectively, suggest that these ligands may be used as a group of anti-Leishmaniasubstances acting selectively on Leishmaniaand different hosts

Calibration of micro-channel plate detector in a Thomson spectrometer for protons and carbon ions with energies below 1 MeV

The calibration of an ion detection system was carried out for protons and carbon ions from a few tens of keV up to about 1 MeV energies. A Thomson spectrometer deflecting the particle beam accelerated from a laser plasma creates the ion spectra on a phosphor screen behind a micro-channel plate (MCP), which are recorded by a camera. During calibration, the ion spectra simultaneously hit the slotted CR-39 track detector installed in front of the MCP and, passing through the adjacent CR-39 stripes, the MCP. The calibration provides the ratio of the interpolated values between two consecutive stripes of the camera signal and the total number of particles recorded on the corresponding stripe of CR-39. The efficiency of proton detection by CR-39 was also measured in a conventional accelerator beam and found to drop by 20% below 100 keV

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit