PO-0940: Feasibility of planning CT to MVCT deformable registration for ìdose of the dayî calculation in helical Tomotherapy

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The Sagnac Effect in curved space-times from an analogy with the Aharonov-Bohm Effect

In the context of the natural splitting, the standard relative dynamics can be expressed in terms of gravito-electromagnetic fields, which allow to formally introduce a gravito-magnetic Aharonov-Bohm effect. We showed elsewhere that this formal analogy can be used to derive the Sagnac effect in flat space-time as a gravito-magnetic Aharonov-Bohm effect. Here, we generalize those results to study the General Relativistic corrections to the Sagnac effect in some stationary and axially symmetric geometries, such as the space-time around a weakly gravitating and rotating source, Kerr space-time, G\"{odel} universe and Schwarzschild space-time.Comment: 14 pages, 1 EPS figure, LaTeX, accepted for publication in General Relativity and Gravitatio

Evaluation of metabolic and biochemical blood parameters in lactating cows with Cystic Ovarian Disease

The aim of the study was to determine and evaluate different blood parameters associated to energetic, protein, mineral and liver metabolic processes together with productive and reproductive parameters in dairy cows of Santa Fe province (Argentina) that were diagnosed with cystic ovarian disease (COD). Lactating Argentine Holstein cows from five dairy herds with spontaneous COD (n= 80) diagnosed by ultrasound and control cows (n= 124) were included in the study. Blood samples were obtained from all cows to determine serum concentrations of: growth hormone, insulin-like growth factor (IGF-1), insulin, aspartate aminotransferase, alkalin phosphatase, gamma glutamiltransferase, albumin, total proteins, albumin: globulin ratio, total and direct bilirrubin, ?-hidroxibutirate, colesterol, glucose, urea, creatinin, calcium, phosphorus and magnesium. Serum concentrations of insulin and IGF-1 were lower (P<0.05) in COD than control cows. No significant differences among groups were observed in any other variables studied, however, the calving to conception interval was higher in cows with COD compared to controls. These results allowed us to conclude that there would be an association between blood concentrations of IGF-1 and insulin and COD that, ultimately, compromise the reproductive performance of the cow.Fil: Cattaneo, L. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Cátedra de Teriogenología. Santa Fe, ArgentinaFil: Barberis, F.C. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Cátedra de Teriogenología. Santa Fe, ArgentinaFil: Stangaferro, M.L. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Cátedra de Teriogenología. Santa Fe, ArgentinaFil: Signorini, M.L. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela. ArgentinaFil: Signorini, M.L. CONICET. ArgentinaFil: Ruiz, M.F. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Hospital de Salud Animal. Santa Fe, ArgentinaFil: Zimmermann, R. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Hospital de Salud Animal. Santa Fe, ArgentinaFil: Bo, G.A. Instituto de Reproducción Animal Córdoba (IRAC). ArgentinaFil: Hein, G.J. CONICET - Universidad Nacional del Litoral. Instituto de Ciencias Veterinarias del Litoral (ICiVet-Litoral). Esperanza, ArgentinaFil: Ortega, H.H. CONICET - Universidad Nacional del Litoral. Instituto de Ciencias Veterinarias del Litoral (ICiVet-Litoral). Esperanza, ArgentinaEl objetivo de este trabajo fue determinar y evaluar indicadores bioquímicos sanguíneos asociados a procesos metabólicos energéticos, proteicos, minerales y de funcionalidad hepática, junto con parámetros productivos y reproductivos en vacas lecheras que fueron diagnosticadas con enfermedad quística ovárica (COD) y controles. Se emplearon vacas Holando Argentino en lactancia de 5 rebaños de la provincia de Santa Fe (Argentina) que presentaban COD (n= 80) diagnosticada mediante ultrasonografía y controles clínicamente sanas (n= 124). De las vacas se obtuvo sangre coccígea para determinar las concentraciones séricas de las hormonas de crecimiento (GH), factor de crecimiento similar a la insulina-1 (IGF-1) e insulina, la actividad sérica de AST, FA, GGT y las concentraciones séricas de albúmina, proteínas totales, relación albúmina: globulinas, bilirrubina total y directa, ?-hidroxibutirato, colesterol, glucosa, urea, creatinina, calcio, fósforo y magnesio. Las concentraciones séricas de insulina e IGF-1 fueron menores (P<0,05) en las vacas con COD que en las controles. No se observaron diferencias significativas (P>0,05) entre ambos grupos en las demás variables séricas y productivas evaluadas, sin embargo, el intervalo parto-concepción fue mayor en vacas que presentaron COD. Los resultados nos permitieron concluir que habría una asociación entre los valores séricos de IGF-1 e insulina y la COD, y que ésta comprometería el futuro reproductivo de las vacas

The relativistic Sagnac Effect: two derivations

The phase shift due to the Sagnac Effect, for relativistic matter and electromagnetic beams, counter-propagating in a rotating interferometer, is deduced using two different approaches. From one hand, we show that the relativistic law of velocity addition leads to the well known Sagnac time difference, which is the same independently of the physical nature of the interfering beams, evidencing in this way the universality of the effect. Another derivation is based on a formal analogy with the phase shift induced by the magnetic potential for charged particles travelling in a region where a constant vector potential is present: this is the so called Aharonov-Bohm effect. Both derivations are carried out in a fully relativistic context, using a suitable 1+3 splitting that allows us to recognize and define the space where electromagnetic and matter waves propagate: this is an extended 3-space, which we call "relative space". It is recognized as the only space having an actual physical meaning from an operational point of view, and it is identified as the 'physical space of the rotating platform': the geometry of this space turns out to be non Euclidean, according to Einstein's early intuition.Comment: 49 pages, LaTeX, 3 EPS figures. Revised (final) version, minor corrections; to appear in "Relativity in Rotating Frames", ed. G. Rizzi and M.L. Ruggiero, Kluwer Academic Publishers, Dordrecht, (2003). See also http://digilander.libero.it/solciclo

Clinical and genetic determinants of nevirapine plasma trough concentration

Background: Only few data are available on the influence of CYP2B6 and CYP3A4/A5 polymorphisms on nevirapine plasma concentrations in the Caucasian population. Our aim was to assess the impact of CYP2B6 and CYP3A4/A5 polymorphisms on nevirapine plasma concentrations consecutively collected. Methods: We retrospectively analyzed clinical data of all HIV-positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan between January 2000 and December 2015. All patients with at least one nevirapine plasma trough concentration (NVP Cmin) determination were tested for CYP2B6 c.516 G>T, CYP3A4*22C>T and CYP3A5*3 A>G polymorphisms. Univariate and multivariate regression analyses were carried out considering NVP Cmin as the dependent variable and genetic polymorphisms and clinical characteristics as independent variables. Results: A total of 143 patients were evaluated. Most of them were males (61.5%) and Caucasian (92.3%). Overall, NVP Cmin varied from 1571 to 14,189\u2009 ng/mL (median\u2009 =\u2009 5063\u2009 ng/mL, interquartile range\u2009 =\u2009 3915\u20136854). The median NVP Cmin significantly differed in patients with different CYP2B6 genotypes, but did not vary in those with different CYP3A phenotypes. In the final general linear model, factors significantly associated with a higher NVP Cmin were each extra unit of T alleles of CYP2B6 rs3745274 (\u3b2\u2009 =\u2009 0.328, 95% confidence interval\u2009 =\u2009 0.172\u20130.484; p\u2009 <\u2009 0.0001), older age (\u3b2\u2009 =\u2009 0.362, 95% confidence interval\u2009 =\u2009 0.193\u20130.532; p\u2009 <\u2009 0.0001) and hepatitis C virus coinfection (\u3b2\u2009 =\u2009 0.161, 95% confidence interval\u2009 =\u2009 0.006\u20130.315; p\u2009 <\u2009 0.041). Conclusion: Our study, conducted in a prevalent Caucasian population, highlighted the importance of CYP2B6 genetic variants in influencing nevirapine plasma trough concentration. Furthermore, older age and hepatitis C virus coinfection significantly increase exposure to nevirapine

Clinical and genetic factors associated with increased risk of severe liver toxicity in a monocentric cohort of HIV positive patients receiving nevirapine-based antiretroviral therapy

BackgroundNevirapine has been used as antiretroviral agent since early 90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its use remains consistent in a certain number of HIV-1-positive subjects. Thus, our aim was to determine clinical and genetic factors involved in the development of severe nevirapine induced liver toxicity.MethodsWe retrospectively analyzed all HIV positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan from May 2011 to December 2015. All patients treated with nevirapine who underwent a genotyping for the functional variants mapping into ABCB1, CYP2B6, CYP3A4 and CYP3A5 genes were included in the analysis. Severe hepatotoxicity was defined as ACTG grade 3-4 AST/ALT increase during the first three months of nevirapine treatment. The causality assessment between NVP exposure and drug-induced liver injury was performed by using the updated Roussel Uclaf Causality Assessment Methods. Hardy Weinberg equilibrium was tested by (2) test. A multivariable logistic regression model was constructed using a backward elimination method.ResultsThree hundred and sixty-two patients were included in the analysis, of which 8 (2.2%) experienced a severe liver toxicity. We observed no differences between patients with and without liver toxicity as regards gender, ethnicity, age and immune-virological status. A higher prevalence of HCV coinfection (75.0% vs 30.2%; p=.0013) and higher baseline AST (58IU/L vs 26IU/L; p=0.041) and ALT (82IU/L vs 27IU/L; p=0.047) median levels were observed in patients with liver toxicity vs those without toxicity. The genotypes CT/TT at ABCB1 rs1045642 single nucleotide polymorphism (SNP), showed a protective effect for liver toxicity when compared with genotype CC (OR=0.18, 95%CI 0.04-0.76; p=0.020) in univariate analysis. In the multivariate model, HCV coinfection was independently associated with higher risk of developing liver toxicity (aOR=8.00, 95%CI 1.27-50.29; p=0.027), whereas ABCB1 rs1045642 CT/TT genotypes (aOR=0.10, 95%CI 0.02-0.47; p=0.004) was associated with a lower risk.ConclusionsAccording to our findings HCV coinfection and ABCB1 rs1045642 SNP represent independent determinants of severe liver toxicity related to nevirapine. This genetic evaluation could be included as toxicity assessment in HIV-1-positive subjects treated with nevirapine

Liposomes in Biology and Medicine

Drug delivery systems (DDS) have become important tools for the specific delivery of a large number of drug molecules. Since their discovery in the 1960s liposomes were recognized as models to study biological membranes and as versatile DDS of both hydrophilic and lipophilic molecules. Liposomes--nanosized unilamellar phospholipid bilayer vesicles--undoubtedly represent the most extensively studied and advanced drug delivery vehicles. After a long period of research and development efforts, liposome-formulated drugs have now entered the clinics to treat cancer and systemic or local fungal infections, mainly because they are biologically inert and biocompatible and practically do not cause unwanted toxic or antigenic reactions. A novel, up-coming and promising therapy approach for the treatment of solid tumors is the depletion of macrophages, particularly tumor associated macrophages with bisphosphonate-containing liposomes. In the advent of the use of genetic material as therapeutic molecules the development of delivery systems to target such novel drug molecules to cells or to target organs becomes increasingly important. Liposomes, in particular lipid-DNA complexes termed lipoplexes, compete successfully with viral gene transfection systems in this field of application. Future DDS will mostly be based on protein, peptide and DNA therapeutics and their next generation analogs and derivatives. Due to their versatility and vast body of known properties liposome-based formulations will continue to occupy a leading role among the large selection of emerging DDS

Prompt K_short production in pp collisions at sqrt(s)=0.9 TeV

The production of K_short mesons in pp collisions at a centre-of-mass energy of 0.9 TeV is studied with the LHCb detector at the Large Hadron Collider. The luminosity of the analysed sample is determined using a novel technique, involving measurements of the beam currents, sizes and positions, and is found to be 6.8 +/- 1.0 microbarn^-1. The differential prompt K_short production cross-section is measured as a function of the K_short transverse momentum and rapidity in the region 0 < pT < 1.6 GeV/c and 2.5 < y < 4.0. The data are found to be in reasonable agreement with previous measurements and generator expectations.Comment: 6+18 pages, 6 figures, updated author lis

Multiwavelength observations of 3C 454.3. III. Eighteen months of agile monitoring of the "crazy diamond"

We report on 18 months of multiwavelength observations of the blazar 3C 454.3 (Crazy Diamond) carried out in the period 2007 July-2009 January. In particular, we show the results of the AGILE campaigns which took place on 2008 May-June, 2008 July-August, and 2008 October-2009 January. During the 2008 May-2009 January period, the source average flux was highly variable, with a clear fading trend toward the end of the period, from an average γ-ray flux F E>100 MeV ≳ 200 × 10-8photonscm -2s-1 in 2008 May-June, to F E>100 MeV 80 × 10-8photonscm-2s-1 in 2008 October-2009 January. The average γ-ray spectrum between 100 MeV and 1 GeV can be fit by a simple power law, showing a moderate softening (from ΓGRID ∼ 2.0 to ΓGRID ∼ 2.2) toward the end of the observing campaign. Only 3σ upper limits can be derived in the 20-60 keV energy band with Super-AGILE, because the source was considerably off-axis during the whole time period. In 2007 July-August and 2008 May-June, 3C 454.3 was monitored by Rossi X-ray Timing Explorer (RXTE). The RXTE/Proportional Counter Array (PCA) light curve in the 3-20 keV energy band shows variability correlated with the γ-ray one. The RXTE/PCA average flux during the two time periods is F 3-20 keV = 8.4 × 10-11ergcm-2s -1, and F 3-20 keV = 4.5 × 10 -11ergcm-2s-1, respectively, while the spectrum (a power law with photon index ΓPCA = 1.65 0.02) does not show any significant variability. Consistent results are obtained with the analysis of the RXTE/High-Energy X-Ray Timing Experiment quasi-simultaneous data. We also carried out simultaneous Swift observations during all AGILE campaigns. Swift/XRT detected 3C 454.3 with an observed flux in the 2-10 keV energy band in the range (0.9-7.5) × 10-11ergcm-2s-1 and a photon index in the range ΓXRT = 1.33-2.04. In the 15-150 keV energy band, when detected, the source has an average flux of about 5mCrab. GASP-WEBT monitored 3C 454.3 during the whole 2007-2008 period in the radio, millimeter, near-IR, and optical bands. The observations show an extremely variable behavior at all frequencies, with flux peaks almost simultaneous with those at higher energies. A correlation analysis between the optical and the γ-ray fluxes shows that the γ-optical correlation occurs with a time lag of τ = -0.4+0.6-0.8 days, consistent with previous findings for this source. An analysis of 15 GHz and 43 GHz VLBI core radio flux observations in the period 2007 July-2009 February shows an increasing trend of the core radio flux, anti-correlated with the higher frequency data, allowing us to derive the value of the source magnetic field. Finally, the modeling of the broadband spectral energy distributions for the still unpublished data, and the behavior of the long-term light curves in different energy bands, allow us to compare the jet properties during different emission states, and to study the geometrical properties of the jet on a time-span longer than one year. © 2010. The American Astronomical Society. All rights reserved