GPU-based ultra-fast direct aperture optimization for online adaptive radiation therapy

Online adaptive radiation therapy (ART) has great promise to significantly reduce normal tissue toxicity and/or improve tumor control through real-time treatment adaptations based on the current patient anatomy. However, the major technical obstacle for clinical realization of online ART, namely the inability to achieve real-time efficiency in treatment re-planning, has yet to be solved. To overcome this challenge, this paper presents our work on the implementation of an intensity modulated radiation therapy (IMRT) direct aperture optimization (DAO) algorithm on graphics processing unit (GPU) based on our previous work on CPU. We formulate the DAO problem as a large-scale convex programming problem, and use an exact method called column generation approach to deal with its extremely large dimensionality on GPU. Five 9-field prostate and five 5-field head-and-neck IMRT clinical cases with 5\times5 mm2 beamlet size and 2.5\times2.5\times2.5 mm3 voxel size were used to evaluate our algorithm on GPU. It takes only 0.7~2.5 seconds for our implementation to generate optimal treatment plans using 50 MLC apertures on an NVIDIA Tesla C1060 GPU card. Our work has therefore solved a major problem in developing ultra-fast (re-)planning technologies for online ART

Could we identify hot Ocean-Planets with CoRoT, Kepler and Doppler velocimetry?

Planets less massive than about 10 MEarth are expected to have no massive H-He atmosphere and a cometary composition (50% rocks, 50% water, by mass) provided they formed beyond the snowline of protoplanetary disks. Due to inward migration, such planets could be found at any distance between their formation site and the star. If migration stops within the habitable zone, this will produce a new kind of planets, called Ocean-Planets. Ocean-planets typically consist in a silicate core, surrounded by a thick ice mantle, itself covered by a 100 km deep ocean. The existence of ocean-planets raises important astrobiological questions: Can life originate on such body, in the absence of continent and ocean-silicate interfaces? What would be the nature of the atmosphere and the geochemical cycles ? In this work, we address the fate of Hot Ocean-Planets produced when migration ends at a closer distance. In this case the liquid/gas interface can disappear, and the hot H2O envelope is made of a supercritical fluid. Although we do not expect these bodies to harbor life, their detection and identification as water-rich planets would give us insight as to the abundance of hot and, by extrapolation, cool Ocean-Planets.Comment: 47 pages, 6 Fugures, regular paper. Submitted to Icaru

Transiting exoplanets from the CoRoT space mission VIII. CoRoT-7b: the first Super-Earth with measured radius

We report the discovery of very shallow (DF/F = 3.4 10-4), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as due to the presence of a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods. We use CoRoT color information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy and preliminary results from Radial Velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star are derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. We examine carefully all conceivable cases of false positives, and all tests performed support the planetary hypothesis. Blends with separation larger than 0.40 arcsec or triple systems are almost excluded with a 8 10-4 risk left. We conclude that, as far as we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 +/- 3 10-5 day and a radius of Rp = 1.68 +/- 0.09 REarth. Analysis of preliminary radial velocity data yields an upper limit of 21 MEarth for the companion mass, supporting the finding. CoRoT-7b is very likely the first Super-Earth with a measured radius.Comment: Accepted in Astronomy and Astrophysics; typos and language corrections; version sent to the printer w few upgrade

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

Cytotoxic drugs efficacy correlates with adipose tissue docosahexaenoic acid level in locally advanced breast carcinoma

Experimental studies indicated that long-chain polyunsaturated fatty acids may increase sensitivity of mammary tumours to several cytotoxic drugs. To evaluate this hypothesis in breast cancer, we have prospectively studied the association between levels of fatty acids stored in breast adipose tissue and the response of the tumour to chemotherapy in 56 patients with an initially localized breast carcinoma. Adipose breast tissue was obtained at the time of biopsy, and individual fatty acids were measured as a percentage of total fatty acids using capillary gas chromatography. Patients then received primary chemotherapy, combining mitoxantrone, vindesine, cyclophosphamide and 5-fluorouracil every 4 weeks. Tumour size was reassessed after three cycles of chemotherapy. Tumour response was evaluated according to World Health Organization criteria. Complete or partial response to chemotherapy was achieved in 26 patients (47%). Level of n-3 polyunsaturated fatty acids in adipose tissue was higher in the group of patients with complete or partial response to chemotherapy than in patients with no response or with tumour progression (P < 0.004). Among n-3 polyunsaturated, only docosahexaenoic acid (22:6n-3) was significantly associated with tumour response (P < 0.005). In a logistic regression analysis taking into account age, body mass index and tumour size, 22:6 n-3 level proved to be an independent predictor for chemosensitivity (P = 0.03). These results suggest that, in breast cancer, 22:6 n-3 may increase the response of the tumour to the cytotoxic agents used. © 1999 Cancer Research Campaig

Combination Therapies Targeting Alk-Aberrant Neuroblastoma in Preclinical Models.

BACKGROUND: ALK activating mutations are identified in approximately 10% of newly diagnosed neuroblastomas and ALK amplifications in a further 1-2% of cases. Lorlatinib, a third generation ALK inhibitor, will soon be given alongside induction chemotherapy for children with ALK-aberrant neuroblastoma. However, resistance to single agent treatment has been reported and therapies that improve the response duration are urgently required. We studied the preclinical combination of lorlatinib with chemotherapy, or with the MDM2 inhibitor, idasanutlin, as recent data has suggested that ALK inhibitor resistance can be overcome through activation of the p53-MDM2 pathway. AIMS: To study the preclinical activity of ALK inhibitors alone and combined with chemotherapy or idasanutlin. METHODS: We compared different ALK inhibitors in preclinical models prior to evaluating lorlatinib in combination with chemotherapy or idasanutlin. We developed a triple chemotherapy (CAV: cyclophosphamide, doxorubicin and vincristine) in vivo dosing schedule and applied this to both neuroblastoma genetically engineered mouse models (GEMM) and patient derived xenografts (PDX). RESULTS: Lorlatinib in combination with chemotherapy was synergistic in immunocompetent neuroblastoma GEMM. Significant growth inhibition in response to lorlatinib was only observed in the ALK-amplified PDX model with high ALK expression. In this PDX lorlatinib combined with idasanutlin resulted in complete tumor regression and significantly delayed tumor regrowth. CONCLUSION: In our preclinical neuroblastoma models, high ALK expression was associated with lorlatinib response alone or in combination with either chemotherapy or idasanutlin. The synergy between MDM2 and ALK inhibition warrants further evaluation of this combination as a potential clinical approach for children with neuroblastoma

Example-based wrinkle synthesis for clothing animation

This paper describes a method for animating the appearance of clothing, such as pants or a shirt, that fits closely to a figure's body. Compared to flowing cloth, such as loose dresses or capes, these types of garments involve nearly continuous collision contact and small wrinkles, that can be troublesome for traditional cloth simulation methods. Based on the observation that the wrinkles in closefitting clothing behave in a predominantly kinematic fashion, we have developed an example-based wrinkle synthesis technique. Our method drives wrinkle generation from the pose of the figure's kinematic skeleton. This approach allows high quality clothing wrinkles to be combined with a coarse cloth simulation that computes the global and dynamic aspects of the clothing motion. While the combined results do not exactly match a high-resolution reference simulation, they do capture many of the characteristic fine-scale features and wrinkles. Further, the combined system runs at interactive rates, making it suitable for applications where high-resolution offline simulations would not be a viable option. The wrinkle synthesis method uses a precomputed database built by simulating the high-resolution clothing as the articulated figure is moved over a range of poses. In principle, the space of poses is exponential in the total number of degrees of freedom; however clothing wrinkles are primarily affected by the nearest joints, allowing each joint to be processed independently. During synthesis, mesh interpolation is used to consider the influence of multiple joints, and combined with a coarse simulation to produce the final results at interactive rates

Transiting exoplanets from the CoRoT space mission. VIII. CoRoT-7b: the first super-Earth with measured radius

Copyright © The European Southern Observatory (ESO)Aims. We report the discovery of very shallow (ΔF/F ≈ 3.4×10−4), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as caused by a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods. We used CoRoT colours information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy, and preliminary results from radial velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star were derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. Results. We examined all conceivable cases of false positives carefully, and all the tests support the planetary hypothesis. Blends with separation >0.40'' or triple systems are almost excluded with a 8 × 10−4 risk left. We conclude that, inasmuch we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 ± 3 × 10−5 day and a radius of Rp = 1.68 ± 0.09 REarth. Analysis of preliminary radial velocity data yields an upper limit of 21 MEarth for the companion mass, supporting the finding. Conclusions. CoRoT-7b is very likely the first Super-Earth with a measured radius. This object illustrates what will probably become a common situation with missions such as Kepler, namely the need to establish the planetary origin of transits in the absence of a firm radial velocity detection and mass measurement. The composition of CoRoT-7b remains loosely constrained without a precise mass. A very high surface temperature on its irradiated face, ≈1800–2600 K at the substellar point, and a very low one, ≈50 K, on its dark face assuming no atmosphere, have been derived

Gaviscon® vs. omeprazole in symptomatic treatment of moderate gastroesophageal reflux. a direct comparative randomised trial

<p>Abstract</p> <p>Background</p> <p>Medical management of GERD mainly uses proton pump inhibitors. Alginates also have proven efficacy. The aim of this trial was to compare short-term efficacy of an alginate (Gaviscon^®, 4 × 10 mL/day) and omeprazole (20 mg/day) on GERD symptoms in general practice.</p> <p>Methods</p> <p>A 14-day multicentre randomised double-blind double-dummy non-inferiority trial compared Gaviscon^®(4 × 10 mL/day) and omeprazole (20 mg/day) in patients with 2-6 day heartburn episodes weekly without alarm signals. The primary outcome was the mean time to onset of the first 24-h heartburn-free period after initial dosing. Secondary outcomes were the proportion of patients without heartburn by D7, pain relief by D7, and reduction in pain intensity by D7 and D14.</p> <p>Results</p> <p>278 patients were recruited; 120 were included in the Gaviscon^®group and 121 in the omeprazole group for the per protocol non-inferiority analysis. The mean time to onset of the first 24-h heartburn-free period after initial dosing was 2.0 (± 2.2) days for Gaviscon^®and 2.0 (± 2.3) days for omeprazole (<it>p </it>= 0.93); mean intergroup difference was 0.01 ± 1.55 days (95% CI = -0.41 to 0.43): i.e., less than the lower limit of the 95% CI of -0.5 days predetermined to demonstrate non-inferiority. The mean number of heartburn-free days by D7 was significantly greater in the omeprazole group: 3.7 ± 2.3 days vs. 3.1 ± 2.1 (<it>p </it>= 0.02). On D7, overall quality of pain relief was slightly in favour of omeprazole (<it>p </it>= 0.049). There was no significant difference in the reduction in pain intensity between groups by D7 (<it>p = </it>0.11) or D14 (<it>p = </it>0.08). Tolerance and safety were good and comparable in both groups.</p> <p>Conclusion</p> <p>Gaviscon^®was non-inferior to omeprazole in achieving a 24-h heartburn-free period in moderate episodic heartburn, and is a relevant effective alternative treatment in moderate GERD in primary care.</p> <p>Trial registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN62203233">ISRCTN62203233</a>.</p