2 Ocena porównawcza dawki w odbytnicy obliczonej dwiema metodami w brachyterapii śródjamowej chorych na raka szyjki i trzonu macicy

WstępW Klinice Onkologii i Radioterapii AMG od 1985 roku stosowana jest brachyterapia cezowa przy użyciu aparatu Selektron LDR. Dawkę maksymalną w odbytnicy do roku 1995 wyznaczano stosując wprowadzony doodbytniczo drucik ołowiany w osłonce plastikowej (R1), a w ostatnich latach zgodnie z zaleceniami Raportu 38 ICRU, dodatkowo oznacza się ją lokalizując tylną ścianę pochwy przez tamponowanie gazikami zawierającymi cieniującą na radiogramach nitkę (R2).Cel pracyPorównanie dawek fizycznych (R1 i R2) i równoważnych im dawek biologicznych (r1 i r2) w odbytnicy, obliczonych powyższymi dwiema metodami.Materiał i metodyAnaliza dotyczyła 124 aplikacji cezu u 102 chorych na raka szyjki lub trzonu macicy, leczonych śródjamowo podczas skojarzonego lub pooperacyjnego napromieniania. Rozkład dawki w miednicy małej obliczano za pomocą komputerowych systemów planowania, wykorzystując 2 prostopadłe radiologiczne zdjęcia lokalizacyjne.Dawki biologiczne obliczono przy pomocy modelu liniowo-kwadratowego, przyjmując α/β=4.WynikiW 83% przypadków wartość bezwzględna dawek R1 była niższa od R2. Wartości średnie dawek R1 i R2 oraz r1 i r2 wynosiły odpowiednio: 13,2 ±4,3 Gy i 16,9 ±4,4 Gy oraz 16,8 ±8,0 Gy i 24,0 ±9,6 Gy. Średnia różnica między R1 i R2 oraz r1 i r2 wynosiła 3,7 Gy (95% CI, 3,03–4,41 Gy) i 7,2 Gy (95% CI, 5,77–8,56 Gy), odpowiednio i jest statystycznie znamienna (

36 Ocena porównawcza dwu metod obliczania dawek w odbytnicy podczas śródjamowej brachyterapii (BT) chorych na raka szyjki i trzonu macicy

Radioterapia nowotworów ginekologicznych wiąże się z wysokim ryzykiem uszkodzeń popromiennych pęcherza i odbytnicy. W skojarzonym leczeniu napromienianiem dawka, jaką otrzymuje pkt referencyjny w odbytnicy stanowi sumę dawek fizycznych z BT śródjamowej oraz napromieniania wiązką zewnętrzną. W Klinice Onkologii i Radioterapii AMG, rozkład dawki w miednicy małej podczas BT obliczany jest komputerowo dla każdej chorej. Punktową dawkę maksymalną w odbytnicy wyznacza się na podstawie wprowadzonego doodbytniczo ołowianego drucika w osłonie plastikowej (R1).Od 1995 roku dodatkowo dawkę tę wyznacza się w punkcie referencyjnym, zgodnie z zaleceniami ICRU (raport Nr 38) lokalizując tylną ścianę pochwy gazikami zawierającymi cieniującą na radiogramach nitkę (R2). Ponadto u wszystkich chorych obliczane są równoważne dawki biologiczne wyliczane z zastosowaniem modelu liniowo-kwadratowego (α/β=4).Celem pracy było porównanie dawek fizycznych i odpowiadających im dawek biologicznych (r1 i r2) obliczonych przy użyciu obu wymienionych metod. Analiza dotyczyła 124 aplikacji cezu u 102 chorych na raka szyjki lub trzonu macicy, leczonych śródjamowo podczas skojarzonego lub pooperacyjnego napromieniania.W 83% przypadków wartość bezwzględna dawek R1 była niższa od R2. Wartości średnie dawek R1 i R2 nosiły odpowiednio: 13,2±4,3 Gy i 16,4±4,4 Gy. Różnica między średnimi wynosząca 3,7 Gy jest zamienna statystycznie (test t-Studenta dla danych sparowanych, p=0,000), zarówno w przypadkach stosowania wyłącznie owoidów jak i pełnego układu (owoidów i sondy domacicznej). Różnica średnich pozostawała znamienna (p=0,016) przy uwzględnieniu 10% błędu metody. Wartości średnie dawek biologicznych r1 i r2 wynosiły odpowiednio: 16,8±8,0 Gy i 24,0±9,6 Gy, a średnia różnica dawek wynosiła 7,2 Gy (p=0,000).WnioskiWykazano istotną różnicę między dawkami wyznaczonymi dwiema metodami. W większości przypadków dawki w odbytnicy wyznaczone przy użyciu doodbytniczego drucika były niższe od dawek obliczonych w punkcie referencyjnym wg ICRU. Wprowadzenie osłon obszaru brachyterapii podczas leczenia wiązką zewnętrzną na podstawie obliczeń dawek R1 oznacza możliwość podania zbyt wysokiej dawki całkowitej na odbytnicę, co zwiększa ryzyko wystąpienia powikłań popromiennych. Z tego powodu metoda obliczenia dawki w odbytnicy przy użyciu doodbytniczego drucika nie powinna być zalecana

Microlens OGLE-2005-BLG-169 Implies Cool Neptune-Like Planets are Common

We detect a Neptune mass-ratio (q~8e-5) planetary companion to the lens star in the extremely high-magnification (A~800) microlensing event OGLE-2005-BLG-169. If the parent is a main-sequence star, it has mass M~0.5 M_sun implying a planet mass of ~13 M_earth and projected separation of ~2.7 AU. When intensely monitored over their peak, high-magnification events similar to OGLE-2005-BLG-169 have nearly complete sensitivity to Neptune mass-ratio planets with projected separations of 0.6 to 1.6 Einstein radii, corresponding to 1.6--4.3 AU in the present case. Only two other such events were monitored well enough to detect Neptunes, and so this detection by itself suggests that Neptune mass-ratio planets are common. Moreover, another Neptune was recently discovered at a similar distance from its parent star in a low-magnification event, which are more common but are individually much less sensitive to planets. Combining the two detections yields 90% upper and lower frequency limits f=0.37^{+0.30}_{-0.21} over just 0.4 decades of planet-star separation. In particular, f>16% at 90% confidence. The parent star hosts no Jupiter-mass companions with projected separations within a factor 5 of that of the detected planet. The lens-source relative proper motion is \mu~7--10 mas/yr, implying that if the lens is sufficiently bright, I<23.8, it will be detectable by HST by 3 years after peak. This would permit a more precise estimate of the lens mass and distance, and so the mass and projected separation of the planet. Analogs of OGLE-2005-BLG-169Lb orbiting nearby stars would be difficult to detect by other methods of planet detection, including radial velocities, transits, or astrometry.Comment: Submitted to ApJ Letters, 9 text pages + 4 figures + 1 tabl

Genes down-regulated in spaceflight are involved in the control of longevity in Caenorhabditis elegans

How microgravitational space environments affect aging is not well understood. We observed that, in Caenorhabditis elegans, spaceflight suppressed the formation of transgenically expressed polyglutamine aggregates, which normally accumulate with increasing age. Moreover, the inactivation of each of seven genes that were down-regulated in space extended lifespan on the ground. These genes encode proteins that are likely related to neuronal or endocrine signaling: acetylcholine receptor, acetylcholine transporter, choline acetyltransferase, rhodopsin-like receptor, glutamate-gated chloride channel, shaker family of potassium channel, and insulin-like peptide. Most of them mediated lifespan control through the key longevity-regulating transcription factors DAF-16 or SKN-1 or through dietary-restriction signaling, singly or in combination. These results suggest that aging in C. elegans is slowed through neuronal and endocrine response to space environmental cues

Microlensing Event MOA-2007-BLG-400: Exhuming the Buried Signature of a Cool, Jovian-Mass Planet

We report the detection of the cool, Jovian-mass planet MOA-2007-BLG-400Lb. The planet was detected in a high-magnification microlensing event (with peak magnification A_max = 628) in which the primary lens transited the source, resulting in a dramatic smoothing of the peak of the event. The angular extent of the region of perturbation due to the planet is significantly smaller than the angular size of the source, and as a result the planetary signature is also smoothed out by the finite source size. Thus the deviation from a single-lens fit is broad and relatively weak (~ few percent). Nevertheless, we demonstrate that the planetary nature of the deviation can be unambiguously ascertained from the gross features of the residuals, and detailed analysis yields a fairly precise planet/star mass ratio of q = 0.0026+/-0.0004, in accord with the large significance (\Delta\chi^2=1070) of the detection. The planet/star projected separation is subject to a strong close/wide degeneracy, leading to two indistinguishable solutions that differ in separation by a factor of ~8.5. Upper limits on flux from the lens constrain its mass to be M < 0.75 M_Sun (assuming it is a main-sequence star). A Bayesian analysis that includes all available observational constraints indicates a primary in the Galactic bulge with a mass of ~0.2-0.5 M_Sun and thus a planet mass of ~ 0.5-1.3 M_Jupiter. The separation and equilibrium temperature are ~0.6-1.1AU (~5.3-9.7AU) and ~103K (~34K) for the close (wide) solution. If the primary is a main-sequence star, follow-up observations would enable the detection of its light and so a measurement of its mass and distance.Comment: 30 pages, 6 figures, Submitted to Ap

Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells

Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca2+) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca2+ signaling in hPAECs by inhibiting the sarco-endoplasmic Ca2+-ATPase (SERCA) which is involved in the regulation of the intracellular Ca2+ homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes

The serum zinc concentration as a potential biological marker in patients with major depressive disorder

Despite many clinical trials assessing the role of zinc in major depressive disorder (MDD), the conclusions still remain ambiguous. The aim of the present clinical study was to determine and comparison the zinc concentration in the blood of MDD patients (active stage or remission) and healthy volunteers (controls), as well as to discuss its potential clinical usefulness as a biomarker of the disease. In this study 69 patients with current depressive episode, 45 patients in remission and 50 controls were enrolled. The zinc concentration was measured by electrothermal atomic absorption spectrometry (ET AAS). The obtained results revealed, that the zinc concentration in depressed phase were statistically lower than in the healthy volunteers [0.89 vs. 1.06 mg/L, respectively], while the zinc level in patients achieve remission was not significantly different from the controls [1.07 vs. 1.06 mg/L, respectively]. Additionally, among the patients achieve remission a significant differences in zinc concentration between group with and without presence of drug-resistance in the previous episode of depression were observed. Also, patients in remission demonstrated correlation between zinc level and the average number of depressive episodes in the last year. Serum zinc concentration was not dependent on atypical features of depression, presence of psychotic symptoms or melancholic syndrome, age, age of onset or duration of disease, number of episodes in the life time, duration of the episode/remission and severity of depression measured by the Hamilton Rating Scale for Depression (HDRS), and the Montgomery-Asberg Depression Rating Scale (MADRS). Concluding, our findings confirm the correlation between zinc deficit present in the depressive episode, and are consistent with the majority of previous studies. These results may also indicate that serum zinc concentration might be considered as a potential biological marker of MDD

On the effects of the fix geometric constraint in 2D profiles on the reusability of parametric 3D CAD models

[EN] In order to be reusable, history-based feature-based parametric CAD models must reliably allow for modifications while maintaining their original design intent. In this paper, we demonstrate that relations that fix the location of geometric entities relative to the reference system produce inflexible profiles that reduce model reusability. We present the results of an experiment where novice students and expert CAD users performed a series of modifications in different versions of the same 2D profile, each defined with an increasingly higher number of fix geometric constraints. Results show that the amount of fix constraints in a 2D profile correlates with the time required to complete reusability tasks, i.e., the higher the number of fix constraints in a 2D profile, the less flexible and adaptable the profile becomes to changes. In addition, a pilot software tool to automatically track this type of constraints was developed and tested. Results suggest that the detection of fix constraint overuse may result in a new metric to assess poor quality models with low reusability. The tool provides immediate feedback for preventing high semantic level quality errors, and assistance to CAD users. Finally, suggestions are introduced on how to convert fix constraints in 2D profiles into a negative metric of 3D model quality.The authors would like to thank Raquel Plumed for her support in the statistical analysis. This work has been partially funded by Grant UJI-A02017-15 (Universitat Jaume I) and DPI201784526-R (MINECO/AEI/FEDER, UE), project CAL-MBE. The authors also wish to thank the editor and reviewers for their valuable comments and suggestions that helped us improve the quality of the paper.González-Lluch, C.; Company, P.; Contero, M.; Pérez Lopez, DC.; Camba, JD. (2019). On the effects of the fix geometric constraint in 2D profiles on the reusability of parametric 3D CAD models. International Journal of Technology and Design Education. 29(4):821-841. https://doi.org/10.1007/s10798-018-9458-zS821841294Ait-Aoudia, S., & Foufou, S. (2010). A 2D geometric constraint solver using a graph reduction method. Advances in Engineering Software, 41(10), 1187–1194. https://doi.org/10.1016/j.advengsoft.2010.07.008 .Ault, H. K. (1999). Using geometric constraints to capture design intent. Journal for Geometry and Graphics, 3(1), 39–45.Ault, H. K. (2004). Over-constrained, under-constrained or just right? Goldilocks evaluates DOF of sketched profiles. Paper presented at American Society for Engineering Education, 59th annual midyear meeting past, present and future? Williamsburg, November 21–23.Ault, H. K., Bu, L., & Liu, K. (2014). Solid modeling strategies-analyzing student choices. Paper presented at proceedings of the 121st ASEE annual conference and exposition, Indianapolis, June 15–18.Ault, H. K., & Fraser, A. (2013). A comparison of manual vs. online grading for solid models. Paper presented at 120th ASEE annual conference and exposition, Atlanta, GA, June 23–26, 2013, Paper ID #7233.Barbero, B. R., Pedrosa, C. M., & Samperio, R. Z. (2016). Learning CAD at university through summaries of the rules of design intent. International Journal of Technology and Design Education. https://doi.org/10.1007/s10798-016-9358-z .Bodein, Y., Bertrand, R., & Caillaud, E. (2014). Explicit reference modeling methodology in parametric CAD system. Computers in Industry, 65(1), 136–147. https://doi.org/10.1016/j.compind.2013.08.004 .Bouma, W., Fudos, I., Hoffmann, C., Cai, J., & Paige, R. (1995). Geometric constraint solver. Computer-Aided Design, 27(6), 487–501. https://doi.org/10.1016/0010-4485(94)00013-4 .Briggs, J. C., Hepworth, A. I., Stone, B. R., Cobum, J. Q., Jensen, C. G., & Red, E. (2015). Integrated, synchronous multi-user design and analysis. Journal of Computing and Information Science in Engineering, 15(3), 031002. https://doi.org/10.1115/1.4029801 .Buckley, J., Seery, N., & Canty, D. (2017). Heuristics and CAD modelling: An examination of student behaviour during problem solving episodes within CAD modelling activities. International Journal of Technology and Design Education. https://doi.org/10.1007/s10798-017-9423-2 .Camba, J. D., & Contero, M. (2015). Assessing the impact of geometric design intent annotations on parametric model alteration activities. Computers in Industry, 71, 35–45. https://doi.org/10.1016/j.compind.2015.03.006 .Camba, J. D., Contero, M., & Company, P. (2016). Parametric CAD modeling: An analysis of strategies for design reusability. Computer-Aided Design, 74, 18–31. https://doi.org/10.1016/j.cad.2016.01.003 .Camba, J. D., Contero, M., & Company, P. (2017). CAD reusability and the role of modeling information in the MBE context. Model-based enterprise summit 2017. National Institute of Standards and Technology (NIST), Gaithersburg, MD, April 3–7. MBE17-020. https://www.nist.gov/file/361581 .Cheng, Z., & Ma, Y. (2017). A functional feature modeling method. Advanced Engineering Informatics, 33, 1–15. https://doi.org/10.1016/j.aei.2017.04.003 .Cheng, Z., Xie, Y., & Ma, Y. (2018). Graph centrality analysis of feature dependencies to unveil modeling intents. Computer-Aided Design and Applications. https://doi.org/10.1080/16864360.2018.1441236 .Chester, I. (2007). Teaching for CAD expertise. International Journal of Technology and Design Education, 17, 23–35. https://doi.org/10.1007/s10798-006-9015-z .Company, P., Contero, M., Otey, J., & Plumed, R. (2015). Approach for developing coordinated rubrics to convey quality criteria in CAD training. Computer-Aided Design, 63, 101–117. https://doi.org/10.1016/j.cad.2014.10.00 .Company, P., & González-Lluch, C. (2013). CAD 3D con SolidWorks ® Tomo I: Diseño básico. Publicacions de la Universitat Jaume I. (Colección Sapientia, Núm. 86). http://cad3dconsolidworks.uji.es .Contero, M., Company, P., Vila, C., & Aleixos, N. (2002). Product data quality and collaborative engineering. IEEE Computer Graphics Applications, 22(3), 32–42. https://doi.org/10.1109/MCG.2002.999786 .Dixon, B. M., & Dannenhoffer, J. F., III. (2014). Geometric sketch constraint solving with user feedback. Journal of Aerospace Information Systems, 11(5), 316–325. https://doi.org/10.2514/1.I010110 .Fudos, I., & Hoffmann, C. M. (1997). A graph-constructive approach to solving systems of geometric constraints. ACM Transactions on Graphics, 16(2), 179–216. https://doi.org/10.1145/248210.248223 .Ge, J. X., Chou, S. C., & Gao, X. S. (1999). Geometric constraint satisfaction using optimization methods. Computer-Aided Design, 31(14), 867–879. https://doi.org/10.1016/S0010-4485(99)00074-3 .González-Lluch, C., Company, P., Contero, M., Camba, J. D., & Colom, J. (2017a). A case study on the use of model quality testing tools for the assessment of MCAD models and drawings. International Journal of Engineering Education, 33(5), 1643–1653.González-Lluch, C., Company, P., Contero, M., Camba, J. D., & Plumed, R. (2017b). A survey on 3D CAD model quality assurance and testing tools. Computer-Aided Design, 83, 64–79. https://doi.org/10.1016/j.cad.2016.10.003 .Hamade, R. F. (2009). Profiling the desirable CAD trainee: Technical background, personality attributes, and learning preferences. Journal of Mechanical Design, 131(12), 121009–121019. https://doi.org/10.1115/1.4000455 .Hekman, K. A., & Gordon, M. T. (2013). Automated grading of first year student CAD work. Paper presented at the 120th ASEE annual conference and exposition 2013, Atlanta, GA, June 23–26. Paper ID #6379.Hepworth, A., Tew, K., Trent, M., Ricks, R., Jensen, C. G., & Red, E. R. (2014). Model consistency and conflict resolution with data preservation in multi-user computer aided design. Journal of Computing and Information Science in Engineering, 14(2), 021008. https://doi.org/10.1115/1.4026553 .Jackson, C., & Buxton, M. (2007). The design reuse benchmark report: Seizing the opportunity to shorten product development. Boston: Aberdeen Group.Joan-Arinyo, R., Soto-Riera, A., Vila-Marta, S., & Vilaplana-Pastó, J. (2003). Transforming an under-constrained geometric constraint problem into a well-constrained one. Paper presented at proceedings of ACM SM03, Seatle, June 16–20.Kirstukas, S. J. (2016). Development and evaluation of a computer program to assess student CAD models. Paper presented at ASEE annual conference and exposition, New Orleans, June 26.Kramer, G. (1991). Using degrees of freedom analysis to solve geometric constraint systems. Paper presented at proceedings of the first ACM symposium on solid modeling foundations and CAD/CAM applications 1991, Austin, June 05–07.Kwon, S., Kim, B. C., Mun, D., & Han, S. (2015). Graph-based simplification of feature-based three-dimensional computer-aided design models for preserving connectivity. Journal of Computing and Information Science in Engineering, 15(3), 031010. https://doi.org/10.1115/1.4030748 .Leea, J. Y., & Kimb, K. (1998). A 2-D geometric constraint solver using DOF-based graph reduction. Computer-Aided Design, 30(11), 883–896. https://doi.org/10.1016/S0010-4485(98)00045-1 .Mata Burgarolas, N. (1997). Solving incidence and tangency constraints in 2D. Technical report LSI-97-3R, Departament LiSI, Universitat Politècnica de Catalunya.Petrina, S. (2003). Two cultures of technical courses and discourses: The case of computer aided design. International Journal of Technology and Design Education, 13, 47–73.Race, P. (2001). The lecturers toolkit—A practical guide to learning, teaching and assessment. Great Britain: Glasgow.Red, E., French, D., Jensen, G., Walker, S. S., & Madsen, P. (2013). Emerging design methods and tools in collaborative product development. Journal of Computing and Information Science in Engineering, 13(3), 031001. https://doi.org/10.1115/1.4023917 .Robertson, B. F., Walther, J., & Radcliffe, D. (2007). Creativity and the use of CAD tools: Lessons for engineering design education from industry. Journal of Mechanical Design, 129(7), 753–760. https://doi.org/10.1115/1.2722329 .Stone, B., Salmon, J., Eves, K., Killian, M., Wright, L., Oldroyd, J., et al. (2017). A multi-user computer-aided design competition: Experimental findings and analysis of team-member dynamics. Journal of Computing and Information Science in Engineering, 17(3), 031003. https://doi.org/10.1115/1.4035674 .Summers, J. D., & Shah, J. J. (2010). Mechanical engineering design complexity metrics: Size, coupling, and solvability. Journal of Mechanical Design, 132(2), 21004–21015. https://doi.org/10.1115/1.4000759 .Szewczyk, J. (2003). Difficulties with the novices’ comprehension of the computer-aided design (CAD) interface: Understanding visual representations of CAD tools. Journal of Engineering Design, 14(2), 169–185. https://doi.org/10.1080/0954482031000091491

The use of spa and phage typing for characterization of clinical isolates of methicillin-resistant Staphylococcus aureus in the University Clinical Center in Gdańsk, Poland

The emergence of spa types and spa–clonal complexes (CC) among clinical methicillin-resistant Staphylococcus aureus isolates collected from the University Clinical Center in Gdańsk between 2008 and 2009 were investigated. Phage typing was used as the initial screening in the study. The basic set of phages and the additional set of phages were used. Most of the isolates (56 %) belonged to the phage group III. With the additional set of phages, eight types were found, with predominant one MR8 (50 %). Sixteen distinct spa types were observed. The most frequent were t003 (22 %), t151 (16 %), and t008 (12 %). The spa types were clustered into two spa-CC and eight singletons. The predominant CC010 (50 %) consisted of six types, with the most common t003 (36.7 %) and t151(26.7 %), and in 80 % was identified as staphylococcal chromosomal casette mec (SCCmec) type II. The second cluster has no founder (12 %) with only two spa types: t037 belonging to SCCmec type III and t029. In the most frequent singleton, spa type t008 alone was clustered in 12 % of the isolates. All singletons correspond to SCCmec type IV. The CC010 was distributed in most of the hospital wards, corresponded to Multilocus sequence typing type ST5/ST225 and was constantly present throughout the observed period. The isolates of CC010 generally belonged to the phage group III, and most of them (53.3 %) were resistant to erythromycin, clindamycin, and ciprofloxacin. The concordance between spa-clone and phage type was very high, but the same phage type MR8 was observed within different spa types of the predominant clone