In intensity modulated particle therapy (IMPT), the adoption of spatially and temporally heterogeneous dose distributions allows to decouple the fractionation scheme from the patient anatomy, so that ...an hypofractionated schedule can be selectively created inside the tumour, while simultaneously exploiting the fractionation effect in the healthy tissues. In this paper, the authors show the reproducibility of the method on a set of prostate patients, quantifying the dependencies of the achievable benefit with respect to conventional and hypofractionated schemes and the sensitivity of the method to setup errors and range uncertainty.
On a cohort of 9 patients, non-uniform IMPT plans were optimised and compared to conventional and hypofractionated schedules. For each patient, the comparison of the three strategies has been based on the output of the cost function used to optimise the treatments. The analysis has been repeated considering different
/
ratios for the tumour, namely 1.5, 3 and 4.5 Gy. For a single patient, setup errors and beam range uncertainty have been analysed: the plans, for each optimisation strategy, have been iteratively forward planned 500 times with randomly varying the patient position in each fraction, and 200 times for systematic range shift.
An average 10% benefit has been shown for the lowest
/
ratio considered for the tumour, where the non-uniform schedule generally converges to hypofractionation; the benefit decreases to 5%-7% for higher
/
ratios, for which the non-uniform schedule always showed better outcomes with respect to the other fractionation schedules. An increased sensitivity to uncertainty, especially for setup errors, has been shown, which can be associated to the spatial non-uniformity of the dose distributions peculiar of the spatiotemporal plans.
This work represents the first investigation of spatiotemporal fractionation for prostate cancer and the beginning of further investigations before clinical implementation can be considered.
The dissipation element analysis is applied to the mixture fraction fields of a series of datasets from direct numerical simulations of non-premixed temporally evolving jet flames with jet Reynolds ...numbers ranging from 4500 to 10 000 and varying stoichiometric mixture fractions. Dissipation elements are space-filling regions where a scalar field behaves monotonically and allow for the analysis of scalar fields in homogeneous isotopic turbulence as well as in complex, highly inhomogeneous and anisotropic flows such as turbulent flames. Statistics of the dissipation element parameters of non-premixed flames are compared to those obtained from non-reacting jets. It is found that the universality of the normalized length distribution of the dissipation elements observed in non-reacting cases also holds true for the reacting flows. The characteristic scaling with the Kolmogorov micro-scale $\eta$ is obtained as well. The effects of combustion on the scalar difference in the dissipation elements are shown and are found to diminish as the Reynolds number and the fuel dilution is increased. The dissipation elements provide the means for a local comparison of the turbulent and characteristic flame scales. A new regime diagram for non-premixed combustion is introduced using coherent structures in the scalar fields, the dissipation element parameters for a local classification of the turbulent flame surface into flamelet-like zones and fine-scale mixing zones in addition to the burning and non-burning zones. The soundness of the regime diagram and the potential consequences for combustion modelling in the individual regimes is demonstrated by the investigation of the correlation between the chemical field and the dissipation element parameters in the individual regimes.
The aim of this study is to investigate how the introduction of Gold nanoparticles GNPs into a skin tumor affects the ability to absorb laser light during multicolor laser exposure. The Monte Carlo ...Geant4 technique was used to construct a cubic geometry simulating human skin, and a 5 mm tumor spheroid was implanted at an adjustable depth x. Our findings show that injecting a very low concentration of 0.01% GNPs into a tumor located 1 cm below the skin’s surface causes significant laser absorption of up to 25%, particularly in the 900 nm to 1200 nm range, resulting in a temperature increase of approximately 20%. It is an effective way to raise a tumor’s temperature and cause cell death while preserving healthy cells. The addition of GNPs to a tumor during polychromatic laser exposure with a wavelength ranging from 900 nm to 1200 nm increases laser absorption and thus temperature while preserving areas without GNPs.
The interaction between the large and the small scales of turbulence is investigated in a mixing layer, at a Reynolds number based on the Taylor microscale (
$Re_{{\it\lambda}}$
) of
$250$
, via ...direct numerical simulations. The analysis is performed in physical space, and the local vorticity root-mean-square (r.m.s.) is taken as a measure of the small-scale activity. It is found that positive large-scale velocity fluctuations correspond to large vorticity r.m.s. on the low-speed side of the mixing layer, whereas, they correspond to low vorticity r.m.s. on the high-speed side. The relationship between large and small scales thus depends on position if the vorticity r.m.s. is correlated with the large-scale velocity fluctuations. On the contrary, the correlation coefficient is nearly constant throughout the mixing layer and close to unity if the vorticity r.m.s. is correlated with the large-scale velocity gradients. Therefore, the small-scale activity appears closely related to large-scale gradients, while the correlation between the small-scale activity and the large-scale velocity fluctuations is shown to reflect a property of the large scales. Furthermore, the vorticity from unfiltered (small scales) and from low pass filtered (large scales) velocity fields tend to be aligned when examined within vortical tubes. These results provide evidence for the so-called ‘scale invariance’ (Meneveau & Katz, Annu. Rev. Fluid Mech., vol. 32, 2000, pp. 1–32), and suggest that some of the large-scale characteristics are not lost at the small scales, at least at the Reynolds number achieved in the present simulation.
Premixed flames exhibit different asymptotic regimes of interaction between heat release and turbulence depending on their respective length scales. At high Karlovitz number, the dilatation caused by ...heat release does not have any relevant effect on turbulent kinetic energy with respect to non-reacting flow, while at low Karlovitz number, the mean shear is a sink of turbulent kinetic energy, and counter-gradient transport is observed. This latter phenomenon is not well captured by closure models commonly used in Large Eddy Simulations that are based on gradient diffusion. The massive amount of data available from Direct Numerical Simulation (DNS) opens the possibility to develop data-driven models able to represent physical mechanisms and non-linear features present in both these regimes. In this work, the databases are formed by DNSs of two planar hydrogen/air flames at different Karlovitz numbers corresponding to the two asymptotic regimes. In this context, the Generative Adversarial Network (GAN) gives the possibility to successfully recognize and reconstruct both gradient and counter-gradient phenomena if trained with databases where both regimes are included. Two GAN models were first trained each for a specific Karlovitz number and tested using the same dataset in order to verify the capability of the models to learn the features of a single asymptotic regime and assess its accuracy. In both cases, the GAN models were able to reconstruct the Reynolds stress subfilter scales accurately. Later, the GAN was trained with a mixture of both datasets to create a model containing physical knowledge of both combustion regimes. This model was able to reconstruct the subfilter scales for both cases capturing the interaction between heat release and turbulence closely to the DNS as shown from the turbulent kinetic budget and barycentric maps.
The calculation algorithm of a modern treatment planning system for ion-beam radiotherapy should ideally be able to deal with different ion species (e.g. protons and carbon ions), to provide relative ...biological effectiveness (RBE) evaluations and to describe different beam lines. In this work we propose a new approach for ion irradiation outcomes computations, the beamlet superposition (BS) model, which satisfies these requirements. This model applies and extends the concepts of previous fluence-weighted pencil-beam algorithms to quantities of radiobiological interest other than dose, i.e. RBE- and LET-related quantities. It describes an ion beam through a beam-line specific, weighted superposition of universal beamlets. The universal physical and radiobiological irradiation effect of the beamlets on a representative set of water-like tissues is evaluated once, coupling the per-track information derived from FLUKA Monte Carlo simulations with the radiobiological effectiveness provided by the microdosimetric kinetic model and the local effect model. Thanks to an extension of the superposition concept, the beamlet irradiation action superposition is applicable for the evaluation of dose, RBE and LET distributions. The weight function for the beamlets superposition is derived from the beam phase space density at the patient entrance. A general beam model commissioning procedure is proposed, which has successfully been tested on the CNAO beam line. The BS model provides the evaluation of different irradiation quantities for different ions, the adaptability permitted by weight functions and the evaluation speed of analitical approaches. Benchmarking plans in simple geometries and clinical plans are shown to demonstrate the model capabilities.
The alpha isotype of actin expressed by hepatic stellate cells reflects their activation to myofibroblast-like cell and has been directly related to experimental liver fibrogenesis, and indirectly to ...human fibrosis in chronic liver disease.
To evaluate the changes in distribution and percentage of alpha-smooth muscle actin-positive hepatic stellate cells and the correlation with the degree of the fibrosis in cirrhotic livers, as well as in patients with recurrent HCV chronic hepatitis after liver transplantation.
Human liver biopsies were divided in four groups: (1) normal livers obtained from cadaveric liver donors (
n
=
35), (2) cirrhosis post-HBV hepatitis (
n
=
11), (3) cirrhosis post-HCV hepatitis (
n
=
10), and (4) post-transplant recurrent HCV chronic hepatitis (
n
=
13). Samples were stained with anti-alpha-smooth muscle actin antibody by immunoperoxidase method and semi-quantitatively evaluated. Liver fibrosis was assessed from specimens stained with Masson's trichrome and quantified by computer image analysis.
The percentage of alpha-smooth muscle actin-positive hepatic stellate cells was significantly higher in the HBV cirrhosis, HCV cirrhosis and post-transplant HCV recurrent hepatitis groups (36.1
±
15.2, 23.8
±
19.7 and 27.8
±
16.4%, respectively) compared to the liver donor group (2.9
±
4.0%). The alpha-smooth muscle actin-positive hepatic stellate cells to fibrous tissue ratio were significantly higher in the post-transplant recurrent HCV hepatitis group (2.36
±
1.12) compared to both the donor livers and the HCV cirrhosis groups (0.74
±
1.09 and 1.03
±
0.91, respectively). The alpha-smooth muscle actin-positive hepatic stellate cell percentage and fibrosis correlated positively in the post-transplant recurrent HCV hepatitis group and negatively in the HCV cirrhosis group. No difference in the immunohistochemical and morphometrical variables was found between the HCV cirrhosis and HBV cirrhosis groups.
These results indirectly confirm that, in vivo, alpha-smooth muscle actin expression is a reliable marker of hepatic stellate cells activation which precedes fibrous tissue deposition even in the setting of recurrent HCV chronic hepatitis after liver transplantation, and it could be useful to identify the earliest stages of hepatic fibrosis and monitoring the efficacy of the therapy. In the presence of advanced cirrhosis other factors, rather than alpha-smooth muscle actin-positive hepatic stellate cells, may sustain fibrosis deposition.
Dissipation element (DE) analysis is a method for analyzing scalar fields in turbulent flows. DEs are defined as a coherent region in which all gradient trajectories of a scalar field reach the same ...extremal points. Therefore, the scalar field can be compartmentalized in monotonous space-filling regions.
The DE analysis is applied to a set of spatially evolving premixed jet flames at different Reynolds numbers. The simulations feature finite rate chemistry with 16 species and 73 reactions. The jet consists of a methane/air mixture with an equivalence ratio φ = 0.7.
Statistics of DE parameters are shown and compared to those of a DNS of a non-reacting spatial jet, a non-reacting temporally evolving jet and isotropic homogeneous turbulence.
The invariance of the normalized length distribution of the DEs toward changes in Reynolds number observed in non-reacting flows holds for the reacting cases and the characteristic scaling with Kolmogorov micro-scale is reproduced. Furthermore, the DE statistics reflect the influence of the premixed flame structure on the turbulent scalar fields.
Corneal ulcers are one of the most common ocular disorders in veterinary ophthalmology and several factors can negatively influence the efficacy of the currently available therapeutic options, ...leading to a loss of corneal transparency and, thus, vision. Twenty-five dogs with clinical signs of corneal ulcers were randomised to receive either corneal phototherapy (16 dogs; study group) or topical standard medical therapy (9 dogs; control group). The riboflavin/UV-A corneal phototherapy (PACK-CXL) consisted in the application of a riboflavin ophthalmic solution (Visioflavin®; Vision Engineering Italy srl, Rome, Italy) onto the cornea for 20 min followed by 30 mW/cm2 UV-A irradiance for 3 min using a point-of-care UV-A device (Vetuvir®; Vision Engineering Italy srl, Rome, Italy). The complete healing of the ulcerative lesion was defined as the complete restoration of the corneal epithelial integrity with negative fluorescein staining. The corneal phototherapy achieved complete corneal healing in all the dogs by 20.5 ± 7.8 days. In the control group, only two dogs achieved complete healing by 21.5 ± 15.6 days. This intervention may represent a valid option to hasten corneal wound healing and a clinical resolution of ulcerative keratitis in dogs.
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