COMPUTATIONAL MODELING OF CELLULAR EFFECTS POST-IRRADIATION WITH LOW- AND HIGH-LET PARTICLES AND DIFFERENT ABSORBED DOSES

The use of computational methods to improve the understanding of biological responses to various types of radiation is an approach where multiple parameters can be modelled and a variety of data is generated. This study compares cellular effects modelled for low absorbed doses against high absorbed doses. The authors hypothesized that low and high absorbed doses would contribute to cell killing via different mechanisms, potentially impacting on targeted tumour radiotherapy outcomes. Cellular kinetics following irradiation with selective low- and high-linear energy transfer (LET) particles were investigated using the Virtual Cell (VC) radiobiology algorithm. Two different cell types were assessed using the VC radiobiology algorithm: human fibroblasts and human crypt cells. The results showed that at lower doses (0.01 to 0.2 Gy), all radiation sources used were equally able to induce cell death (p\u3e0.05, ANOVA). On the other hand, at higher doses (1.0 to 8.0 Gy), the radiation response was LET and dose dependent (p\u3c0.05, ANOVA). The data obtained suggests that the computational methods used might provide some insight into the cellular effects following irradiation. The results also suggest that it may be necessary to re-evaluate cellular radiation-induced effects, particularly at low doses that could affect therapeutic effectiveness

Palliative treatment of metastatic bone pain with radiopharmaceuticals: a perspective beyond Strontium-89 and Samarium-153

PurposeThe present review article aims to provide an overview of the available radionuclides for palliative treatment of bone metastases beyond 89Sr and 153Sm. In addition, it aims to review and summarize the clinical outcomes associated with the palliative treatment of bone metastases using different radiopharmaceuticals.Materials and methodsA literature search was conducted on Science Direct and PubMed databases (1990 - 2015). The following search terms were combined in order to obtain relevant results: bone, metastases, palliative, care, therapy, treatment, radiotherapy, review, radiopharmaceutical, phosphorus-32, strontium-89, yttrium-90, tin-117m, samarium-153, holmium-166, thulium-170, lutetium-177, rhenium-186, rhenium-188 and radium-223. Studies were included if they provided information regarding the clinical outcomes.Results and conclusionsA comparative analysis of the measured therapeutic response of different radiopharmaceuticals, based on previously published data, suggests that there is a lack of substantial differences in palliative efficacy among radiopharmaceuticals. However, when the comparative analysis adds factors such as patients life expectancy, radionuclides physical characteristics (e.g. tissue penetration range and half-life) and health economics to guide the rational selection of a radiopharmaceutical for palliative treatment of bone metastases, 177Lu and 188Re-labeled radiopharmaceuticals appear to be the most suitable radiopharmaceuticals for treatment of small and medium/large size bone lesions, respectively

Princípios gerais de culturas de células e citometria de fluxo para avaliação dos efeitos da radiação ionizante

Este relatório tem por objectivos expor em os princípios gerais de cultura de células e da citometria de fluxo para análise dos efeitos da radiação ionizante em culturas de células. Assim, conceitos relacionados com culturas de células, incluindo tipos de culturas e vantagens e desvantagens, são expostos no presente relatório. Adicionalmente, o princípio da técnica de citometria de fluxo, bem como, o seu uso em estudos dos efeitos da radiação ionizante em culturas de células, são igualmente apresentados.This report aims to explain in the basic principles of cells culture and flow citometry for the study of ionizing radiation effects on cells culture. Thus, subjects such as cells culture type and advantages/disadvantages of cells culture are explained. Additionally, basic principles of flow citometry, as well as, its applicability for the study of ionizing radiation effects on cell culture are also presented

Computational modeling of radiobiological effects in bone metastases for different radionuclides

: Computational simulation is a simple and practical way to study and to compare a variety ofradioisotopes for different medical applications, including the palliative treatment of bone metastases. Thisstudy aimed to evaluate and compare cellular effects modelled for different radioisotopes currently in use orunder research for treatment of bone metastases using computational methods.Methods: Computational models were used to estimate the radiation-induced cellular effects (VirtualCell Radiobiology algorithm) post-irradiation with selected particles emitted by Strontium-89 (89Sr),Samarium-153 (153Sm), Lutetium-177 (177Lu), and Radium-223 (223Ra).Results: Cellular kinetics post-irradiation using 89Sr β- particles, 153Sm β− particles, 177Lu β− particles and 223Raα particles showed that the cell response was dose- and radio- nuclide-dependent. 177Lu beta minus particlesand, in particular, 223Ra alpha particles, yielded the lowest survival fraction of all investigated particles.Conclusions: 223Ra alpha particles induced the highest cell death of all investigated particles on metastaticprostate cells in comparison to irradiation with β− radionuclides, two of the most frequently used radionuclidesin the palliative treatment of bone metastases in clinical routine practice. Moreover, the data obtained suggestthat the used computational methods might provide some perception about cellular effects following irradiationwith different radionuclides

Speeding up optimum-path forest training by path-cost propagation

In this paper we present an optimization of the Optimum-Path Forest classifier training procedure, which is based on a theoretical relationship between minimum spanning forest and optimum-path forest for a specific path-cost function. Experiments on public datasets have shown that the proposed approach can obtain similar accuracy to the traditional one hut with faster data training

Comparative analysis of 11 different radioisotopes for palliative treatment of bone metastases by computational methods

Purpose: Throughout the years, the palliative treatment of bone metastases using bone seeking radiotracers has been part of the therapeutic resources used in oncology, but the choice of which bone seeking agent to use is not consensual across sites and limited data are available comparing the characteristics of each radioisotope. Computational simulation is a simple and practical method to study and to compare a variety of radioisotopes for different medical applications, including the palliative treatment of bone metastases. This study aims to evaluate and compare 11 different radioisotopes currently in use or under research for the palliative treatment of bone metastases using computational methods. Methods: Computational models were used to estimate the percentage of deoxyribonucleic acid (DNA) damage (fast Monte Carlo damage algorithm), the probability of correct DNA repair (Monte Carlo excision repair algorithm), and the radiation-induced cellular effects (virtual cell radiobiology algorithm) post-irradiation with selected particles emitted by phosphorus-32 (P-32), strontium-89 (Sr-89), yttrium-90 (Y-90), tin-117 (Sn-117m), samarium-153 (Sm-153), holmium-166 (Ho-166), thulium-170 (Tm-170), lutetium-177 (Lu-177), rhenium-186 (Re-186), rhenium-188 (Re-188), and radium-223 (Ra-223). Results: Ra-223 alpha particles, Lu-177 beta minus particles, and Tm-170 beta minus particles induced the highest cell death of all investigated particles and radioisotopes. The cell survival fraction measured post-irradiation with beta minus particles emitted by Sr-89 and Sm-153, two of the most frequently used radionuclides in the palliative treatment of bone metastases in clinical routine practice, was higher than Lu-177 beta minus particles and Ra-223 alpha particles. Conclusions: Ra-223 and Lu-177 hold the highest potential for palliative treatment of bone metastases of all radioisotopes compared in this study. Data reported here may prompt future in vitro and in vivo experiments comparing different radionuclides for palliative treatment of bone metastases, raise the need for the careful rethinking of the current widespread clinical use of Sr-89 and Sm-153, and perhaps strengthen the use of Ra-223 and Lu-177 in the palliative treatment of bone metastases. (C) 2014 American Association of Physicists in Medicine

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt