Experimental validation in a neutron exposure frame of the MINAS TIRITH for cell damage simulation.

In the domains of medicine and space exploration, refining risk assessment models for protecting healthy tissue from ionizing radiation is crucial. Understanding radiation-induced effects requires biological experimentations at the cellular population level and the cellular scale modeling using Monte Carlo track structure codes. We present MINAS TIRITH, a tool using Geant4-DNA Monte Carlo-generated databases to study DNA damage distribution at the cell population scale. It introduces a DNA damage location module and proposes a method to convert double-strand breaks (DSB) into DNA Damage Response foci. We evaluate damage location precision and DSB-foci conversion parameters. MINAS TIRITH's accuracy is validated againstγ-H2AX foci distribution from cell population exposed to monoenergetic neutron beams (2.5 or 15.1 MeV) under different configurations, yielding mixed radiation fields. Strong agreement between simulation and experimental results was found demonstrating MINAS TIRITH's predictive precision in radiation-induced DNA damage topology. Additionally, modeling intercellular damage variability within a population subjected to a specific macroscopic dose identifies subpopulations, enhancing realistic fate models. This approach advances our understanding of radiation-induced effects on cellular systems for risk assessment improvement.

MINAS TIRITH: a new tool for simulating radiation-induced DNA damage at the cell population level.

Objective. The mechanisms of radiation-induced DNA damage can be understood via the fundamental acquisition of knowledge through a combination of experiments and modeling. Currently, most biological experiments are performed by irradiating an entire cell population, whereas modeling of radiation-induced effects is usually performed via Monte Carlo simulations with track structure codes coupled to realistic DNA geometries of a single-cell nucleus. However, the difference in scale between the two methods hinders a direct comparison because the dose distribution in the cell population is not necessarily uniform owing to the stochastic nature of the energy deposition. Thus, this study proposed the MINAS TIRITH tool to model the distribution of radiation-induced DNA damage in a cell population.Approach. The proposed method is based on precomputed databases of microdosimetric parameters and DNA damage distributions generated using the Geant4-DNA Monte Carlo Toolkit. First, a specific energyzwas assigned to each cell of an irradiated population for a particular absorbed doseDabs,following microdosimetric formalism. Then, each cell was assigned a realistic number of DNA damage events according to the specific energyz,respecting the stochastic character of its occurrence.Main results. This study validated the MINAS TIRITH tool by comparing its results with those obtained using the Geant4-DNA track structure code and a Geant4-DNA based simulation chain for DNA damage calculation. The different elements of comparison indicated consistency between MINAS TIRITH and the Monte Carlo simulation in case of the dose distribution in the population and the calculation of the amount of DNA damage.Significance. MINAS TIRITH is a new approach for the calculation of radiation-induced DNA damage at the cell population level that facilitates reasonable simulation times compared to those obtained with track structure codes. Moreover, this tool enables a more direct comparison between modeling and biological experimentation.

Future development of biologically relevant dosimetry.

Proton and ion beams are radiotherapy modalities of increasing importance and interest. Because of the different biological dose response of these radiations as compared with high-energy photon beams, the current approach of treatment prescription is based on the product of the absorbed dose to water and a biological weighting factor, but this is found to be insufficient for providing a generic method to quantify the biological outcome of radiation. It is therefore suggested to define new dosimetric quantities that allow a transparent separation of the physical processes from the biological ones. Given the complexity of the initiation and occurrence of biological processes on various time and length scales, and given that neither microdosimetry nor nanodosimetry on their own can fully describe the biological effects as a function of the distribution of energy deposition or ionization, a multiscale approach is needed to lay the foundation for the aforementioned new physical quantities relating track structure to relative biological effectiveness in proton and ion beam therapy. This article reviews the state-of-the-art microdosimetry, nanodosimetry, track structure simulations, quantification of reactive species, reference radiobiological data, cross-section data and multiscale models of biological response in the context of realizing the new quantities. It also introduces the European metrology project, Biologically Weighted Quantities in Radiotherapy, which aims to investigate the feasibility of establishing a multiscale model as the basis of the new quantities. A tentative generic expression of how the weighting of physical quantities at different length scales could be carried out is presented.

Reciprocal angulation of vertebral bodies in a sagittal plane: approach to references for the evaluation of kyphosis and lordosis.

In order to establish a sagittal plane curve reference table for standing subjects examined laterally, we determined an easily reproducible standard posture. A sample of 100 healthy subjects from 20 to 29 years of age, was chosen (43 women, 57 men). The reciprocal angulations of each vertebral body in relation to the others were fed into a digitalizer and studied by computer. The study particularly concerns maximum kyphosis, maximum lordosis, sacral base slopes, and the tilt of intermediate vertebral bodies. The dispersion of the results is remarkably wide and, within the extreme values, the distribution is irregular. Individual correlations of these values are often dispersed, but spinal morphotypology. For considerable lengths, average values cannot be used as norms, given the wide span of values. Only the extreme limits are useful for the appreciation of curves as excessive, insufficient, or inverted.

[Combination of methylmethacrylate (acrylic cement) and antibiotics. Bacteriologic and mechanical study]. / Association méthacrylate de méthyle (ciment acrylique) et antibiotiques. Etude bactériologique et mécanique.

The authors report the results of a study about the association of acrylic cement with antibiotics. Three cements have been tested: Simplex, CMW, Palacos, with 14 different antibiotics. A series of experiments has been carried out in three phases: a macroscopic study of the polymerisation of the mixture; in vitro bacteriological studies; and mechanical studies (trials of resistance to traction, flexion, shock measuring the modulus of elasticity and hardness). In vivo bacteriological testings have been carried out on 10 patients. It has come out from this study that the polymerisation of cement, usually does not destroy antibiotics which remain active and that the mechanical properties of cement are modified in sundry manners. All additions of tested antibiotics modifie mechanical properties by about 25 p. 100 but some additions seem to be preferable. Improvements must still be made and confirmed by this type of research.

[Anterior strut grafting in kyphosis and kyphoscoliosis (author's transl)]. / Greffes antérieures en étai dans le traitement des cyphoses et cyphoscolioses.

The authors have reviewed 58 cases submitted to strut grafting in the concavity of the curve. There were 44 kyphoscolioses and 12 kyphoses. The average follow-up was more than two years and the average pre-operative deformity was 127 degrees. The average improvement was 38 degrees and the secondary loss was only 3 degrees. The results are analysed with regard to the surgical technique used. In some cases, posterior fixation was added and the graft was either from the tibia, the fibula or a rib. In 16 cases a secondary fracture of the graft was found. It appeared between the fourth and tenth post-operative months. During this period, reduction of the graft was seen. The graft was found to thicken later at about the eighteenth post-operative month. It is concluded that the technique is worthwhile provided it is associated with posterior internal fixation, and that an external brace is worn for at least eighteen months after operation.

[Lumbar venography in the diagnosis of disc herniation (author's transl)]. / Apport de la phlébographie lombaire dans le diagnostic des hernies discales.

The authors have performed lumbar venography on 120 occasions in patients with low back pain. In 58 patients in whom the herniated disc was confirmed, the result of venography was positive and the localisation was precise in 67 cases. It is concluded that the method is safe, reliable and allows precision in diagnosis to allow better selection for surgical treatment. The examination is particularly useful in recurrent sciatica, fractures of the lumbar spine, recent or old, and in spinal stenosis. It may be associated with discography when the result is not clear cut.

[Fracture of the odontoid process (author's transl)]. / Fractures de l'apophyse odontoïde (dens) de l'axis. 102 cas dont 73 fractures récentes.

102 cases of fractures of the odontoid process have been seen by the author - 73 recent cases and 29 old ones. It was important to distinguish basal fractures (29 cases), which all united after conservative treatment by reduction and skull traction for six weeks followed by a plaster cast for six to eight weeks, and fractures of the body (44 cases). 41 body fractures were treated conservatively, of which 6 died and only 20 united. The authors consider that treatment by skull traction must always be tried. An eventual indication for surgery can be made at about the 20th day if displacement is found to be present in spite of treatment. Fusion in these cases must be limited to C1-C2. It is best obtained by a combination of wiring and grafting.