407 research outputs found
A closed parameterization of DNA-damage by charged particles as a function of energy - A geometrical approach
Purpose: To present a closed formalism calculating charged particle radiation
damage induced in DNA. The formalism is valid for all types of charged
particles and due to its closed nature is suited to provide fast conversion of
dose to DNA-damage. Methods: The induction of double strand breaks in
DNA--strings residing in irradiated cells is quantified using a single particle
model. This leads to a proposal to use the cumulative Cauchy distribution to
express the mix of high and low LET type damage probability generated by a
single particle. A microscopic phenomenological Monte Carlo code is used to fit
the parameters of the model as a function of kinetic energy related to the
damage to a DNA molecule embedded in a cell. The model is applied for four
particles: electrons, protons, alpha--particles, and carbon ions. A geometric
interpretation of this observation using the impact ionization mean free path
as a quantifier, allows extension of the model to very low energies. Results:
The mathematical expression describes the model adequately using a chi--square
test (). This applies to all particle types with an almost
perfect fit for protons, while the other particles seem to result in some
discrepancies at very low energies. The implementation calculating a strict
version of the RBE based on complex damage alone is corroborated by
experimental data from the measured RBE. The geometric interpretation generates
a unique dimensionless parameter for each type of charged particle. In
addition, it predicts a distribution of DNA damage which is different from the
current models.Comment: 19 pages, 15 figures and 1 appendi
09021 Abstracts Collection -- Software Service Engineering
From 04.01. to 07.01.2009, the Dagstuhl Seminar 09021 ``Software Service Engineering \u27\u27 was held in Schloss Dagstuhl~--~Leibniz Center for Informatics.
During the seminar, several participants presented their current
research, and ongoing work and open problems were discussed. Abstracts of
the presentations given during the seminar as well as abstracts of
seminar results and ideas are put together in this paper. The first section
describes the seminar topics and goals in general.
Links to extended abstracts or full papers are provided, if available
Companding technique for high dynamic range measurements using gafchromic films
We propose a methodology to perform dose measurements using gafchromic films
which can span several decades of dose levels. The technique is based on a
rescaling approach using different films irradiated at different dose levels.
This is combined with a registration protocol correcting positioning and
scaling factors for each film.Comment: Preprint submitted to Medical Physics, 10 pages, 4 figures, 1 tabl
Modeling early haematologic adverse events in conformal and intensity-modulated pelvic radiotherapy in anal cancer
AbstractBackground and purposeTo determine if there are differences between dose to pelvic bone marrow (PBM) using intensity modulated radiotherapy (IMRT) under UK guidance versus conformal radiotherapy (CRT) per ACT II protocol and if differences translate to rates of early haematological adverse events grade 3 or greater (HT3+).Methods and materialsTwo groups of 20+ patients, treated under IMRT and CRT regimes respectively, were identified. All patients underwent weekly blood cell count: haemoglobin (HgB), white cell count (WCC), absolute neutrophil count (ANC) and platelets (plats).Percent volume of PBM and sub structures receiving 5–25Gy were tested for statistical significance. Regression models were used to test for correlation to blood counts. NTCP modeling was also performed.ResultsPMB dose metrics showed a significant increase in the IMRT group. Regression analysis showed iliac and lumbosacral PBM dose metrics to associate with reduced nadir ANC and WCC. NTCP at HT3+ was 0.13 using IMRT relative to 0.07 using CRT (p<0.05).ConclusionWhilst this is a relatively small retrospective study and lacks information on the distribution of active PBM, IMRT treatment has been shown to significantly increase PMB irradiation. PBM dose metrics have been shown to be predictive of WCC and ANC suppression. NTCP modeling predicts much high risk of HT3+. Paradoxically, actual rates of HT3+ were comparable suggesting that differences in the distributions of dose metrics maybe a significant factor and/or that there are insufficiency in the NTCP modeling
Stereotactic body radiotherapy for moderately central and ultra-central oligometastatic disease: initial outcomes
Background:
Delivery of SBRT to central thoracic tumours within 2 cm of the proximal bronchial tree (PBT), and especially ultra-central tumours which directly abut the PBT, has been controversial due to concerns about high risk of toxicity and treatment-related death when delivering high doses close to critical mediastinal structures. We present dosimetric and clinical outcomes from a group of oligometastatic patients treated with a risk-adapted SBRT approach.
Methods:
Between September 2015 and October 2018, 27 patients with 28 central thoracic oligometastases (6 moderately central, 22 ultra-central) were treated with 60 Gy in 8 fractions under online CBCT guidance. PTV dose was compromised where necessary to meet mandatory OAR constraints. Patients were followed up for toxicity and disease status.
Results:
Mandatory OAR constraints were met in all cases; this required PTV coverage compromise in 23 cases, with V100% reduced to <70% in 11 cases. No acute or late toxicities of Grade ≥ 3 were reported. One and 2 year in-field control rates were 95.2% and 85.7% respectively, progression-free survival rates were 42.8% and 23.4% respectively, and overall survival rates were 82.7% and 69.5% respectively. No significant differences were seen in control or survival rates by extent of PTV underdosage or between moderately and ultra-central cases.
Conclusion:
It appears that compromising PTV coverage to meet OAR constraints allows safe and effective delivery of SBRT to moderately and ultra-central tumours, with low toxicity rates and high in-field control rates. This treatment can be delivered on standard linear accelerators with widely available imaging technology
Adrenal function in adult long-term survivors of nephroblastoma and neuroblastoma
AbstractBackgroundAdrenal insufficiency, or relative insufficiency, might partly explain increased mortality rates in nephroblastoma and neuroblastoma survivors after unilateral adrenalectomy.ObjectiveTo assess adrenal function and its metabolic effects in survivors after adrenalectomy.MethodsIn this cross-sectional study, 67 adult long-term survivors of nephroblastoma, 36 survivors of neuroblastoma and 49 control subjects participated. Adrenal function was assessed by a 1μg short Synacthen-test. Levels of cortisol, adrenocorticotrophic hormone (ACTH), low (LDL-C) and high-density lipoprotein-cholesterol (HDL-C), triglycerides, apolipoprotein-B, glucose and insulin were assessed in blood samples taken at baseline. In addition, cortisol levels were assessed after 30 (t=30) and 60min. Homoeostatic Model Assessment (HOMA) was calculated.ResultsAdrenal insufficiency was not present in survivors. Interestingly, baseline serum cortisol levels were higher in survivors after unilateral adrenalectomy (mean 503nmol/l) (N=46) than in survivors with both adrenals intact (mean 393nmol/l, P=0.002) (N=52), and than in controls (mean 399nmol/l, P=0.013) (N=49). After correcting for age, sex and use of oral oestrogens, unilateral adrenalectomy was independently associated with elevated baseline cortisol and ACTH levels. Baseline cortisol levels were positively associated with triglycerides (P<0.001), LDL-C (P=0.004), apolipoprotein-B (P<0.001) and HOMA (P=0.008).ConclusionsNo adrenal insufficiency was observed in survivors of nephroblastoma and neuroblastoma. Survivors treated with unilateral adrenalectomy had relatively high basal cortisol and ACTH levels, indicating a higher central setpoint of the hypothalamic-pituitary-adrenal axis. This higher setpoint was associated with lipid concentrations and insulin resistance and can therefore influence the cardiovascular risk profile in long-term survivors of nephroblastoma and neuroblastoma
Hydrodynamics of the stream-disk impact in interacting binaries
We use hydrodynamic simulations to provide quantitative estimates of the
effects of the impact of the accretion stream on disks in interacting binaries.
For low accretion rates, efficient radiative cooling of the hotspot region can
occur, and the primary consequence of the stream impact is stream overflow
toward smaller disk radii. The stream is well described by a ballistic
trajectory, but larger masses of gas are swept up and overflow at smaller, but
still highly supersonic, velocities. If cooling is inefficient, overflow still
occurs, but there is no coherent stream inward of the disk rim. Qualitatively,
the resulting structure appears as a bulge extending downstream along the disk
rim. We calculate the mass fraction and velocity of the overflowing component
as a function of the important system parameters, and discuss the implications
of the results for X-ray observations and doppler tomography of cataclysmic
variables, low-mass X-ray binaries and supersoft X-ray sources.Comment: 16 pages, including 8 figures. 1 color figure as a jpeg. ApJ, in
pres
Transcriptome sequencing reveals two subtypes of cortisol-secreting adrenocortical tumours in dogs and identifies CYP26B1 as a potential new therapeutic target
Cushing's syndrome (CS) is a serious endocrine disorder that is relatively common in dogs, but rare in humans. In ~15%–20% of cases, CS is caused by a cortisol-secreting adrenocortical tumour (csACT). To identify differentially expressed genes that can improve prognostic predictions after surgery and represent novel treatment targets, we performed RNA sequencing on csACTs (n = 48) and normal adrenal cortices (NACs; n = 10) of dogs. A gene was declared differentially expressed when the adjusted p-value was 2 or < −2. Between NACs and csACTs, 98 genes were differentially expressed. Based on the principal component analysis (PCA) the csACTs were separated in two groups, of which Group 1 had significantly better survival after adrenalectomy (p =.002) than Group 2. Between csACT Group G1 and Group 2, 77 genes were differentially expressed. One of these, cytochrome P450 26B1 (CYP26B1), was significantly associated with survival in both our canine csACTs and in a publicly available data set of 33 human cortisol-secreting adrenocortical carcinomas. In the validation cohort, CYP26B1 was also expressed significantly higher (p =.012) in canine csACTs compared with NACs. In future studies it would be interesting to determine whether CYP26B1 inhibitors could inhibit csACT growth in both dogs and humans
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