Variational Approach to Hard Sphere Segregation Under Gravity

It is demonstrated that the minimization of the free energy functional for hard spheres and hard disks yields the result that excited granular materials under gravity segregate not only in the widely known "Brazil nut" fashion, i.e. with the larger particles rising to the top, but also in reverse "Brazil nut" fashion. Specifically, the local density approximation is used to investigate the crossover between the two types of segregation occurring in the liquid state, and the results are found to agree qualitatively with previously published results of simulation and of a simple model based on condensation.Comment: 10 pages, 3 figure

Evaluation of robustly optimised intensity modulated proton therapy for nasopharyngeal carcinoma

BACKGROUND AND PURPOSE: To evaluate the dosimetric changes occurring over the treatment course for nasopharyngeal carcinoma (NPC) patients treated with robustly optimised intensity modulated proton therapy (IMPT). MATERIALS AND METHODS: 25 NPC patients were treated to two dose levels (CTV1: 70Gy, CTV2: 54.25Gy) with robustly optimised IMPT plans. Robustness evaluation was performed over 28 error scenarios using voxel-wise minimum distributions to assess target coverage and voxel-wise maximum distributions to assess possible hotspots and critical organ doses. Daily CBCT was used for positioning and weekly repeat CTs (rCT) were taken, on which the plan dose was recalculated and robustly evaluated. Deformable image registration was used to warp and accumulate the nominal, voxel-wise minimum and maximum rCT dose distributions. Changes to target coverage, critical organ and normal tissue dose between the accumulated and planned doses were investigated. RESULTS: 2 patients required a plan adaptation due to reduced target coverage. The D98% in the accumulated voxel-wise minimum distribution was higher than planned for CTV1 in 24/25 patients and for CTV2 in 20/25 patients. Maximum doses to the critical organs remained acceptable in all patients. Other normal tissue doses showed some variation as a result of soft tissue deformations and weight change. Normal tissue complication probabilities for grade ≥2 dysphagia and grade ≥2 xerostomia remained similar to planned values. CONCLUSION: Robustly optimised IMPT plans, in combination with volumetric verification imaging and adaptive planning, provided robust target coverage and acceptable OAR dose variation in our NPC cohort when accumulated over longitudinal data

Head and neck IMPT probabilistic dose accumulation:Feasibility of a 2 mm setup uncertainty setting

OBJECTIVE: To establish optimal robust optimization uncertainty settings for clinical head and neck cancer (HNC) patients undergoing 3D image-guided pencil beam scanning (PBS) proton therapy. METHODS: We analyzed ten consecutive HNC patients treated with 70 and 54.25 GyRBE to the primary and prophylactic clinical target volumes (CTV) respectively using intensity-modulated proton therapy (IMPT). Clinical plans were generated using robust optimization with 5 mm/3% setup/range uncertainties (RayStation v6.1). Additional plans were created for 4, 3, 2 and 1 mm setup and 3% range uncertainty and for 3 mm setup and 3%, 2% and 1% range uncertainty. Systematic and random error distributions were determined for setup and range uncertainties based on our quality assurance program. From these, 25 treatment scenarios were sampled for each plan, each consisting of a systematic setup and range error and daily random setup errors. Fraction doses were calculated on the weekly verification CT closest to the date of treatment as this was considered representative of the daily patient anatomy. RESULTS: Plans with a 2 mm/3% setup/range uncertainty setting adequately covered the primary and prophylactic CTV (V95≥ 99% in 98.8% and 90.8% of the treatment scenarios respectively). The average organ-at-risk dose decreased with 1.1 GyRBE/mm setup uncertainty reduction and 0.5 GyRBE/1% range uncertainty reduction. Normal tissue complication probabilities decreased by 2.0%/mm setup uncertainty reduction and by 0.9%/1% range uncertainty reduction. CONCLUSION: The results of this study indicate that margin reduction below 3 mm/3% is possible but requires a larger cohort to substantiate clinical introduction

Development of advanced preselection tools to reduce redundant plan comparisons in model-based selection of head and neck cancer patients for proton therapy

PURPOSE: In the Netherlands, head and neck cancer (HNC) patients are selected for proton therapy (PT) based on estimated normal tissue complication probability differences (ΔNTCP) between photons and protons, which requires a plan comparison (VMAT vs. IMPT). We aimed to develop tools to improve patient selection for plan comparisons. METHODS: This prospective study consisted of 141 consecutive patients in which a plan comparison was done. IMPT plans of patients not qualifying for PT were classified as 'redundant'. To prevent redundant IMPT planning, 5 methods that were primarily based on regression models were developed to predict IMPT Dmean to OARs, by using data from VMAT plans and volumetric data from delineated targets and OARs. Then, actual and predicted plan comparison outcomes were compared. The endpoint was being selected for proton therapy. RESULTS: Seventy out of 141 patients (49.6%) qualified for PT. Using the developed preselection tools, redundant IMPT planning could have been prevented in 49-68% of the remaining 71 patients not qualifying for PT (=specificity) when the sensitivity of all methods was fixed to 100%, i.e., no false negative cases (positive predictive value range: 57-68%, negative predictive value: 100%). CONCLUSION: The advanced preselection tools, which uses volume and VMAT dose data, prevented labour intensive creation of IMPT plans in up to 68% of non-qualifying patients for PT. No patients qualifying for PT would have been incorrectly denied a plan comparison. This method contributes significantly to a more cost-effective model-based selection of HNC patients for PT

The impacts of environmental warming on Odonata: a review

Climate change brings with it unprecedented rates of increase in environmental temperature, which will have major consequences for the earth's flora and fauna. The Odonata represent a taxon that has many strong links to this abiotic factor due to its tropical evolutionary history and adaptations to temperate climates. Temperature is known to affect odonate physiology including life-history traits such as developmental rate, phenology and seasonal regulation as well as immune function and the production of pigment for thermoregulation. A range of behaviours are likely to be affected which will, in turn, influence other parts of the aquatic ecosystem, primarily through trophic interactions. Temperature may influence changes in geographical distributions, through a shifting of species' fundamental niches, changes in the distribution of suitable habitat and variation in the dispersal ability of species. Finally, such a rapid change in the environment results in a strong selective pressure towards adaptation to cope and the inevitable loss of some populations and, potentially, species. Where data are lacking for odonates, studies on other invertebrate groups will be considered. Finally, directions for research are suggested, particularly laboratory studies that investigate underlying causes of climate-driven macroecological patterns

A comparative evaluation of various invasion assays testing colon carcinoma cell lines

Various colon carcinoma cell lines were tested in different invasion assays, i.e. invasion into Matrigel, into confluent fibroblast layers and into chicken heart tissue. Furthermore, invasive capacity and metastatic potential were determined in nude mice. The colon carcinoma cells used were the human cell lines Caco-2, SW-480, SW-620 and HT-29, and the murine lines Colon-26 and -38. None of the human colon carcinoma cells migrated through porous membranes coated with Matrigel; of the murine lines, only Colon-26 did. When incubated in a mixture of Matrigel and culture medium non-invading cells formed spheroid cultures, whereas invading cells showed a stellate outgrowth. Only the heterogeneously shaped (epithelioid and stellate) cells of SW-480 and SW-620 and the spindle-shaped cells of Colon-26 invaded clearly confluent skin and colon fibroblasts as well as chicken heart tissue. However, when transplanted into the caecum of nude and syngeneic mice, all the lines tested were invasive with the exception of Caco-2 cells. We conclude that the outcome of in vitro tests measuring the invasive capacity of neoplastic cells is largely dependent on the test system used. Invasive capacity in vitro is strongly correlated with cells having a spindle cell shape, vimentin expression and E-cadherin down regulation. In contrast, HT-29 and Colon-38 cells having an epithelioid phenotype were clearly invasive and metastatic in vivo, but not in vitro. © 1999 Cancer Research Campaig

Prenatal parental tobacco smoking, gene specific DNA methylation, and newborns size: the Generation R study

Background: Deleterious effects of prenatal tobacco smoking on fetal growth and newborn weight are well-established. One of the proposed mechanisms underlying this relationship is alterations in epigenetic programming. We selected 506 newborns from a population-based prospective birth cohort in the Netherlands. Prenatal parental tobacco smoking was assessed using self-reporting questionnaires. Information on birth outcomes was obtained from medical records. The deoxyribonucleic acid (DNA) methylation of the growth genes IGF2DMR and H19 was measured in newborn umbilical cord white blood cells. Associations were assessed between parental tobacco smoking and DNA methylation using linear mixed models and adjusted for potential confounders. Results: The DNA methylation levels of IGF2DMR and H19 in the non-smoking group were median (90 % range), 54.0 % (44.6–62.0), and 30.0 % (25.5–34.0), in the first trimester only smoking group 52.2 % (44.5–61.1) and 30.8 % (27.1–34.1), and in the continued smoking group 51.6 % (43.9–61.3) and 30.2 % (23.7–34.8), respectively. Continued prenatal maternal smoking was inversely associated with IGF2DMR methylation (β = −1.03, 95 % CI −1.76; −0.30) in a dose-dependent manner (P-trend = 0.030). This association seemed to be slightly more profound among newborn girls (β = −1.38, 95 % CI −2.63; −0.14) than boys (β = −0.72, 95 % CI −1.68; 0.24). H19 methylation was also inversely associated continued smoking <5 cigarettes/day (β = −0.96, 95 % CI −1.78; −0.14). Moreover, the association between maternal smoking and newborns small for gestational age seems to be partially explained by IGF2DMR methylation (β = −0.095, 95 % CI −0.249; −0.018). Among non-smoking mothers, paternal tobacco smoking was not associated with IGF2DMR or H19 methylation. Conclusions: Maternal smoking is inversely associated with IGF2DMR methylation in newborns, which can be one of the underlying mechanisms through which smoking affects fetal growth

IMRT commissioning: multiple institution planning and dosimetry comparisons, a report from AAPM Task Group 119.

AAPM Task Group 119 has produced quantitative confidence limits as baseline expectation values for IMRT commissioning. A set of test cases was developed to assess the overall accuracy of planning and delivery of IMRT treatments. Each test uses contours of targets and avoidance structures drawn within rectangular phantoms. These tests were planned, delivered, measured, and analyzed by nine facilities using a variety of IMRT planning and delivery systems. Each facility had passed the Radiological Physics Center credentialing tests for IMRT. The agreement between the planned and measured doses was determined using ion chamber dosimetry in high and low dose regions, film dosimetry on coronal planes in the phantom with all fields delivered, and planar dosimetry for each field measured perpendicular to the central axis. The planar dose distributions were assessed using gamma criteria of 3%/3 mm. The mean values and standard deviations were used to develop confidence limits for the test results using the concept confidence limit = /mean/ + 1.96sigma. Other facilities can use the test protocol and results as a basis for comparison to this group. Locally derived confidence limits that substantially exceed these baseline values may indicate the need for improved IMRT commissioning