Comment on 'Implications on clinical scenario of gold nanoparticle radiosensitization in regards to photon energy, nanoparticle size, concentration and location'

A recent paper by Lechtman et al (2011 Phys. Med. Biol. 56 4631-47) presented Monte Carlo modelling of gold nanoparticle dose modification. In it, they predict that the introduction of gold nanoparticles has the strongest effect with x-rays at kilovoltage energies, and that negligible increases in dose are expected at megavoltage energies. While these results are in agreement with others in the literature (including those produced by our group), the conclusion that '(goldnanoparticle) radiosensitization using a 6 MV photon source is not clinically feasible' appears to conflict with recently published experimental studies which have shown radiosensitization using 6 MV x-ray sources with relatively low gold concentrations. The increasing disparity between theoretical predictions of dose enhancement and experimental results in the field of gold nanoparticle radiosensitization suggests that, while the ability of gold nanoparticles to modify dose within a tumour volume is well understood, the resulting radiosensitization is not simply correlated with this measure. This highlights the need to validate theoretical predictions of this kind against experimental measurements, to ensure that the scenarios and values being modelled are meaningful within a therapeutic context.

Dosimetry and spectral analysis of a radiobiological experiment using laser-driven proton beams

Laser-driven proton and ion acceleration is an area of increasing research interest given the recent development of short pulse-high intensity lasers. Several groups have reported experiments to understand whether a laser-driven beam can be applied for radiobiological purposes and in each of these, the method to obtain dose and spectral analysis was slightly different. The difficulty with these studies is that the very large instantaneous dose rate is a challenge for commonly used dosimetry techniques, so that other more sophisticated procedures need to be explored. This paper aims to explain a method for obtaining the energetic spectrum and the dose of a laser-driven proton beam irradiating a cell dish used for radiobiology studies. The procedure includes the use of a magnet to have charge and energy separation of the laser-driven beam, Gafchromic films to have information on dose and partially on energy, and a Monte Carlo code to expand the measured data in order to obtain specific details of the proton spectrum on the cells. Two specific correction factors have to be calculated: one to take into account the variation of the dose response of the films as a function of the proton energy and the other to obtain the dose to the cell layer starting from the dose measured on the films. This method, particularly suited to irradiation delivered in a single laser shot, can be applied in any other radiobiological experiment performed with laser-driven proton beams, with the only condition that the initial proton spectrum has to be at least roughly known. The method was tested in an experiment conducted at Queen's University of Belfast using the TARANIS laser, where the mean energy of the protons crossing the cells was between 0.9 and 5 MeV, the instantaneous dose rate was estimated to be close to 10(9) Gy s(-1) and doses between 0.8 and 5 Gy were delivered to the cells in a single laser shot. The combination of the applied corrections modified the initial estimate of dose by up to 40%.

Evidence for a hypoxic fixation reaction leading to the induction of ssb and dsb in irradiated DNA

Purpose: To measure hypoxic chemical fixation processes of radiation damage in both isolated plasmid DNA and in GSH-depleted E. coli cells.

A comparison of the radiosensitivity of relaxed and supercoiled plasmid DNA

Purpose: The aim of the work was to compare critically the radiosensitivity of the supercoiled and relaxed forms of a plasmid DNA system commonly used in DNA damage assays.

Critical energies for ssb and dsb induction in plasmid DNA by vacuum-UV photons: an arrangement for irradiating dry or hydrated DNA with monochromatic photons

Purpose: Theoretical modelling techniques are often used to simulate the action of ionizing radiations on cells at the nanometre level, Using monoenergetic vacuum-UV (VUV) radiation to irradiate DNA either dry or humidified, the action spectra for the induction of DNA damage by low energy photons and the role of water and can be studied. These data provide inputs for the theoretical models.

Critical energies for SSB and DSB induction in plasmid DNA by low-energy photons: action spectra for strand-break induction in plasmid DNA irradiated in vacuum

Purpose: To measure action spectra for the induction of single- strand breaks (SSB) and double-strand breaks (DSB) in plasmid DNA by low-energy photons and provide estimates for the energy dependence of strand-break formation important for track-structure simulations of DNA damage.

The relationship between the RBE of alpha particles and the radiosensitivity of different mutations of Chinese hamster cells

The RBE of alpha -particles in different mutations of Chinese hamster cells was determined with the aim of identifying differences in the sensitivity to x-ray and alpha -particle-induced DNA damage. Two parental lines of Chinese hamster cells and four radiosensitive mutants were irradiated with different single doses of x-rays and alpha -particles and clonogenic cell survival was determined. Radiosensitivity to x-rays varied by a factor of 5 between the cell strains whereas sensitivity to alpha -particle irradiation was almost identical among all strains. The RBE is only determined by the sensitivity of the cells towards x-rays. Since cells with different defects of repair or cell cycle control have different radiosensitivities, we conclude that the effects of x-ray irradiation and the RBE are mostly determined by the activity of repair processes.

A Monte Carlo model of DNA double-strand break clustering and rejoining kinetics for the analysis of pulsed-field gel electrophoresis data

In studies of radiation-induced DNA fragmentation and repair, analytical models may provide rapid and easy-to-use methods to test simple hypotheses regarding the breakage and rejoining mechanisms involved. The random breakage model, according to which lesions are distributed uniformly and independently of each other along the DNA, has been the model most used to describe spatial distribution of radiation-induced DNA damage. Recently several mechanistic approaches have been proposed that model clustered damage to DNA. In general, such approaches focus on the study of initial radiation-induced DNA damage and repair, without considering the effects of additional (unwanted and unavoidable) fragmentation that may take place during the experimental procedures. While most approaches, including measurement of total DNA mass below a specified value, allow for the occurrence of background experimental damage by means of simple subtractive procedures, a more detailed analysis of DNA fragmentation necessitates a more accurate treatment. We have developed a new, relatively simple model of DNA breakage and the resulting rejoining kinetics of broken fragments. Initial radiation-induced DNA damage is simulated using a clustered breakage approach, with three free parameters: the number of independently located clusters, each containing several DNA double-strand breaks (DSBs), the average number of DSBs within a cluster (multiplicity of the cluster), and the maximum allowed radius within which DSBs belonging to the same cluster are distributed. Random breakage is simulated as a special case of the DSB clustering procedure. When the model is applied to the analysis of DNA fragmentation as measured with pulsed-field gel electrophoresis (PFGE), the hypothesis that DSBs in proximity rejoin at a different rate from that of sparse isolated breaks can be tested, since the kinetics of rejoining of fragments of varying size may be followed by means of computer simulations. The problem of how to account for background damage from experimental handling is also carefully considered. We have shown that the conventional procedure of subtracting the background damage from the experimental data may lead to erroneous conclusions during the analysis of both initial fragmentation and DSB rejoining. Despite its relative simplicity, the method presented allows both the quantitative and qualitative description of radiation-induced DNA fragmentation and subsequent rejoining of double-stranded DNA fragments. (C) 2004 by Radiation Research Society.

Calcium fluxes modulate the radiation-induced bystander responses in targeted glioma and fibroblast cells

Bystander responses have been reported to be a major determinant of the response of cells to radiation exposure at low doses, including those of relevance to therapy. This study investigated the role of changes in calcium levels in bystander responses leading to chromosomal damage in nonirradiated T98G glioma cells and AG01522 fibroblasts that had been either exposed to conditioned medium from irradiated cells or co-cultured with a population where a fraction of cells were individually targeted through the nucleus or cytoplasm with a precise number of microbeam helium-3 particles. After the recipient cells were treated with conditioned medium from T98G or AG01522 cells that had been irradiated through either nucleus or cytoplasm, rapid calcium fluxes were monitored in the nonirradiated recipient cells. Their characteristics were dependent on the source of the conditioned medium but had no dependence on radiation dose. When recipient cells were co-cultured with an irradiated population of either T98G or AG01522 cells, micronuclei were induced in the nonirradiated cells, but this response was eliminated by treating the cells with calcicludine (CaC), a potent blocker of Ca2+ channels. Moreover, both the calcium fluxes and the bystander effect were inhibited when the irradiated T98G cells were treated with aminoguanidine, an inhibitor of nitric oxide synthase (NOS), and when the irradiated AG01522 cells were treated with DMSO, a scavenger of reactive oxygen species (ROS), which indicates that NO and ROS were involved in the bystander responses generated from irradiated T98G and AG01522 cells, respectively. Our findings indicate that calcium signaling may be an early response in radiation-induced bystander effects leading to chromosome damage. (c) 2006 by Radiation Research Society.

Radiation effects on the cytoskeleton of endothelial cells and endothelial monolayer permeability

Purpose: To investigate the effects of radiation on the endothelial cytoskeleton and endothelial monolayer permeability and to evaluate associated signaling pathways, which could reveal potential mechanisms of known vascular effects of radiation.

Association between participation in life situations of children with cerebral palsy and their physical, social, and attitudinal environment:A cross-sectional multicenter European study

Objective:
To evaluate how participation of children with cerebral palsy (CP) varied with their environment.

Design:
Home visits to children. Administration of Assessment of Life Habits and European Child Environment Questionnaires. Structural equation modeling of putative associations between specific domains of participation and environment, while allowing for severity of child's impairments and pain.

Setting:
European regions with population-based registries of children with CP.

Participants:
Children (n=1174) aged 8 to 12 years were randomly selected from 8 population-based registries of children with CP in 6 European countries. Of these, 743 (63%) agreed to participate; 1 further region recruited 75 children from multiple sources. Thus, there were 818 children in the study.

Interventions:
Not applicable.

Main Outcome Measure:
Participation in life situations.

Results:
For the hypothesized associations, the models confirmed that higher participation was associated with better availability of environmental items. Higher participation in daily activities—mealtimes, health hygiene, personal care, and home life—was significantly associated with a better physical environment at home (P<.01). Mobility was associated with transport and physical environment in the community. Participation in social roles (responsibilities, relationships, recreation) was associated with attitudes of classmates and social support at home. School participation was associated with attitudes of teachers and therapists. Environment explained between 14% and 52% of the variation in participation.

Conclusions:
The findings confirmed the social model of disability. The physical, social, and attitudinal environment of disabled children influences their participation in everyday activities and social roles.

Millimeter-wave and submillimeter-wave imaging for security and surveillance

Passive equipments operating in the 30-300 GHZ (millimeter wave) band are compared to those in the 300 GHz-3 THz (submillimeter band). Equipments operating in the submillimeter band can measure distance and also spectral information and have been used to address new opportunities in security. Solid state spectral information is available in the submillimeter region making it possible to identify materials, whereas in millimeter region bulk optical properties determine the image contrast. The optical properties in the region from 30 GHz to 3 THz are discussed for some typical inorganic and organic solids. in the millimeter-wave region of the spectrum, obscurants such as poor weather, dust, and smoke can be penetrated and useful imagery generated for surveillance. in the 30 GHZ-3 THZ region dielectrics such as plastic and cloth are also transparent and the detection of contraband hidden under clothing is possible. A passive millimeter-wave imaging concept based on a folded Schmidt camera has been developed and applied to poor weather navigation and security. The optical design uses a rotating mirror and is folded using polarization techniques. The design is very well corrected over a wide field of view making it ideal for surveillance, and security. This produces a relatively compact imager which minimizes the receiver count.

Surface localisation of photosensitisers on intraocular lens biomaterials for prevention of infectious endophthalmitis and retinal protection

Cataract surgery is one of the most commonly-practiced surgical procedures in Western medicine, and, while complications are rare, the most serious is infectious postoperative endophthalmitis. Bacteria may adhere to the implanted intraocular lens (IOL) and subsequent biofilm formation can lead to a chronic, difficult to treat infection. To date, no method to reduce the incidence of infectious endophthalmitis through bacterial elimination, while retaining optical transparency, has been reported. In this study we report a method to optimise the localisation of a cationic porphyrin at the surface of suitable acrylate copolymers, which is the first point of contact with potential pathogens. The porphyrin catalytically generates short-lived singlet oxygen, in the presence of visible light, which kills adherent bacteria indiscriminately. By restricting the photosensitiser to the surface of the biomaterial, reduction in optical transparency is minimised without affecting efficacy of singlet oxygen production. Hydrogel IOL biomaterials incorporating either methacrylic acid (MAA) or methyl methacrylate (MMA) co-monomers allow tuning of the hydrophobic and anionic properties to optimise the localisation of porphyrin. Physiochemical and antimicrobial properties of the materials have been characterised, giving candidate materials with self-generating, persistent anti-infective character against Gram-positive and Gram-negative organisms. Importantly, incorporation of porphyrin can also serve to protect the retina by filtering damaging shortwave visible light, due to the Soret absorption (?max) 430 nm). © 2012 Elsevier Ltd. All rights reserved.