Purpose
In view of the potential of treatment plan optimization based on nanodosimetric quantities, fast Monte Carlo methods for obtaining nanodosimetric quantities in macroscopic volumes are ...important. In this work, a “fast” method for obtaining nanodosimetric parameters from a clinical proton pencil beam in a macroscopic volume is compared with a slow and detailed method. Furthermore, the variations of these parameters, when obtained with the Monte Carlo codes TOPAS and NOREC, are investigated.
Methods
Monte Carlo track structure simulations of 1 keV–100 MeV protons and 12 eV–1 MeV electrons in a volume of 8 nm
3 liquid water provided us with an atlas of cluster size distributions. Two kinds of ionization cluster size distributions were recorded, counting all ionizations or only ionizations directly produced by the primary particle. The simulations of the proton pencil beam were performed in two different ways. A “fast” method where only the protons were simulated and a “slow and detailed” method where protons and electrons were simulated in order to obtain spectra at different depths. The obtained spectra were then convoluted with cluster size distributions.
Results
It was shown that the nanodosimetric quantity
F2 from the “fast” method is, depending on the location, between 43.6% and 63.6% smaller than the
F2 obtained by the “slow and detailed” method. However, it was also shown that variations of nanodosimetric quantities are even larger when the cluster size distributions of the electrons are simulated with the Monte Carlo code NOREC, that is, the cumulative
F2 probabilities obtained with NOREC were between 50.8% and 75.5% smaller than the
F2 probabilities obtained with TOPAS.
Conclusions
As long as the uncertainties of different Monte Carlo codes are not improved, it is feasible to only simulate protons in a macroscopic volume. It must be noted, however, that the uncertainty is in the order of 100%.
A simple model for cell survival which is valid also at high dose has been developed. The model parameters can be traced back to measurable quantities from nanodosimetry. It is assumed that a cell is ...killed by an event which is defined by two or more double strand breaks in differently sized lethal interaction volumes (LIVs). Two different mechanisms can produce events, one-track events by one-particle track and two-track events by two. One- and two-track events are statistically independent. From the stochastic nature of cell killing which is described by the Poisson distribution, the cell survival probability was derived. The ratio of the number of one- and two-track events can be directly expressed in terms of nanodosimetry by the probability F2 that at least two ionizations are produced in a basic interaction volume (5-10 base pairs). From the model, relative biological effectiveness (RBE) can be derived which depends only on F2 and the size of the LIV. The expression for RBE fits experimental data with satisfying quality.
A radiation action model based on nanodosimetry is presented. It is motivated by the finding that the biological effects of various types of ionizing radiation lack a consistent relation with ...absorbed dose. It is postulated that the common fundamental cause of these effects is the production of elementary sublesions (DSB), which are created at a rate that is proportional to the probability to produce more than two ionisations within a volume of 10 base pairs of the DNA. The concepts of nanodosimetry allow for a quantitative characterization of this process in terms of the cumulative probability
F
2
. The induced sublesions can interact in two ways to produce lethal damage. First, if two or more sublesions accumulate in a locally limited spherical volume of 3–10 nm in diameter, clustered DNA damage is produced. Second, consequent interactions or rearrangements of some of the initial damage over larger distances (~ µm) can produce additional lethal damage. From the comparison of theoretical predictions deduced from this concept with experimental data on relative biological effectiveness, a cluster volume with a diameter of 7.5 nm could be determined. It is shown that, for electrons, the predictions agree well with experimental data over a wide energy range. The only free parameter needed to model cell survival is the intersection cross-section which includes all relevant cell-specific factors. Using ultra-soft X-rays it could be shown that the energy dependence of cell survival is directly governed by the nanodosimetric characteristics of the radiation track structure. The cell survival model derived in this work exhibits exponential cell survival at a high dose and a finite gradient of cell survival at vanishing dose, as well as the dependence on dose-rate.
Abstract Numerical weather prediction models operate on grid spacings of a few kilometers, where deep convection begins to become resolvable. Around this scale, the emergence of coherent structures ...in the planetary boundary layer, often hypothesized to be caused by cold pools, forces the transition from shallow to deep convection. Yet, the kilometer-scale range is typically not resolved by standard surface operational measurement networks. The measurement campaign Field Experiment on Submesoscale Spatio-Temporal Variability in Lindenberg (FESSTVaL) aimed at addressing this gap by observing atmospheric variability at the hectometer-to-kilometer scale, with a particular emphasis on cold pools, wind gusts, and coherent patterns in the planetary boundary layer during summer. A unique feature was the distribution of 150 self-developed and low-cost instruments. More specifically, FESSTVaL included dense networks of 80 autonomous cold pool loggers, 19 weather stations, and 83 soil sensor systems, all installed in a rural region of 15-km radius in eastern Germany, as well as self-developed weather stations handed out to citizens. Boundary layer and upper-air observations were provided by eight Doppler lidars and four microwave radiometers distributed at three supersites; water vapor and temperature were also measured by advanced lidar systems and an infrared spectrometer; and rain was observed by a X-band radar. An uncrewed aircraft, multicopters, and a small radiometer network carried out additional measurements during a 4-week period. In this paper, we present FESSTVaL’s measurement strategy and show first observational results including unprecedented highly resolved spatiotemporal cold-pool structures, both in the horizontal as well as in the vertical dimension, associated with overpassing convective systems.
There is no consensus regarding the terminology, definition, classification, diagnostic criteria, and algorithm, or reporting standards for the disease of infective native aortic aneurysm (INAA), ...previously known as mycotic aneurysm. The aim of this study was to establish this by performing a consensus study.
The Delphi methodology was used. Thirty-seven international experts were invited via mail to participate. Four two week Delphi rounds were performed, using an online questionnaire, initially with 22 statements and nine reporting items. The panellists rated the statements on a five point Likert scale. Comments on statements were analysed, statements revised, and results presented in iterative rounds. Consensus was defined as ≥ 75% of the panel selecting “strongly agree” or “agree” on the Likert scale, and consensus on the final assessment was defined as Cronbach’s alpha coefficient > .80.
All 38 panellists completed all four rounds, resulting in 100% participation and agreement that this study was necessary, and the term INAA was agreed to be optimal. Three more statements were added based on the results and comments of the panel, resulting in a final 25 statements and nine reporting items. All 25 statements reached an agreement of ≥ 87%, and all nine reporting items reached an agreement of 100%. The Cronbach’s alpha increased for each consecutive round (round 1 = .84, round 2 = .87, round 3 = .90, and round 4 = .92). Thus, consensus was reached for all statements and reporting items.
This Delphi study established the first consensus document on INAA regarding terminology, definition, classification, diagnostic criteria, and algorithm, as well as reporting standards. The results of this study create essential conditions for scientific research on this disease. The presented consensus will need future amendments in accordance with newly acquired knowledge.
Evidence is lacking to guide the management of infective native aortic aneurysm (INAA). The aim of this study was to establish expert consensus on surgical and antimicrobial treatment and follow up, ...and to define when an INAA is considered cured.
Delphi methodology was used. The principal investigators invited 47 international experts (specialists in infectious diseases, radiology, nuclear medicine, and vascular and cardiothoracic surgery) via email. Four Delphi rounds were performed, three weeks each, using an online questionnaire with initially 28 statements. The panellists rated the statements on a five point Likert scale. Comments on statements were analysed, statements were revised and added or deleted, and the results were presented in the iterative rounds. Consensus was defined as ≥ 75% of the panel rating a statement as strongly agree or agree on the Likert scale, and consensus on the final assessment was defined as Cronbach’s alpha > 0.80.
All 49 panellists completed all four rounds, resulting in 100% participation. One statement was added based on the results and comments of the panel, resulting in 29 final statements: three on need for consensus, 20 on treatment, five on follow up, and one on definition of cure. All 29 statements reached agreement of ≥ 86%. Cronbach’s alpha increased for each consecutive round; round 1, 0.85; round 2, 0.90; round 3, 0.91; and round 4, 0.94. Thus, consensus was reached for all statements.
INAAs are rare, and high level evidence to guide optimal management is lacking. This consensus document was established with the aim of helping clinicians manage these challenging patients, as a supplement to current guidelines. The presented consensus will need future amendments in accordance with newly acquired knowledge.
PDF
