CT-based tumour response criteria compared after combined treatment for liver metastases of colorectal cancer

open6noPurpose: The aim of this analysis is to compare different tumour response criteria (TRC) after chemotherapy combined with bevacizumab in liver metastases from colorectal cancer (mCRC) to ascertain the best early prognostic indicator of response. Methods and Materials: 103 target liver metastases from 65 mCRC patients treated with chemoterapy plus bevacizumab were examined at the Istituto Oncologico Veneto IOV-IRCSS (March 2008-January 2013). All patients had baseline CT and at least one follow-up scan. Tumour response was retrospectively analyzed by two radiologists using RECIST1.1, modified Choi, and Chun morphologic criteria. Tumour response, classified as good (complete or partial response) or poor (stable or progressive disease), was compared with progression-free survival (PFS) at first follow-up (t1) and time of best response. Interobserver agreement and concordance between TRC were measured. Results: At t1, 32.31% showed a good response according to RECIST1.1 (median PFS 11.1), 84.62% according to Choi (median PFS 10.8). These percentages rose to 49.23% (median PFS 12.1) and 87.69% (median PFS 10.8), respectively, at the time of best response. According to Chun, 67.69% showed a good response at the time of best response (median PFS 10.8). The Choi criteria detected a higher proportion of good responders at t1, showing a better correlation with PFS; all methods correlated with PFS at the time of best response. Conclusion: The Choi criteria proved more consistent in the early detection of response in mCRC treated with chemotherapy plus bevacizumab, underscoring the importance of using these criteria in the early assessment of response to combined treatment.openopenVarotto, A.; Di Grazia, L.; Aliberti, C.; Bergamo, F.; Nardin, M.; Pomerri, F.Varotto, A.; Di Grazia, L.; Aliberti, C.; Bergamo, F.; Nardin, M.; Pomerri, Fabi

Genotoxicity assessment of piperitenone oxide: an in vitro and in silico evaluation

Piperitenone oxide, a natural flavouring agent also known as rotundifolone, has been studied for the genotoxicity assessment by an integrated in vitro and in silico experimental approach, including the bacterial reverse mutation assay, the micronucleus test, the comet assay and the computational prediction by Toxtree and VEGA tools. Under our experimental conditions, the monoterpene showed to induce both point mutations (i.e. frameshift, base-substitution and/or oxidative damage) and DNA damage (i.e. clastogenic or aneuploidic damage, or single-strand breaks). Computational prediction for piperitenone oxide agreed with the toxicological data, and highlighted the presence of the epoxide function and the α,β-unsaturated carbonyl as possible structural alerts for DNA damage. However, improving the toxicological libraries for natural occurring compounds is required in order to favour the applicability of in silico models to the toxicological predictions. Further in vivo evaluations are strictly needed in order to evaluate the role of the bioavailability of the substance and the metabolic fate on its genotoxicity profile. To the best of our knowledge, these data represent the first evaluation of the genotoxicity for this flavour compound and suggest the need of further studies to assess the safety of piperitenone oxide as either flavour or fragrance chemicals

A Source Identification Problem for the Electrical Activity of Brain During Hand Movement

A field source reconstruction of the dipoles modeling the activated area of the brain, while a subject performs the task of the voluntary motion of the hand, is solved. Experimental data resulting from fMRI are used for constraining the position of the equivalent dipole

In vivo genetic manipulation of inner ear connexin expression by bovine adeno-Associated viral vectors

We have previously shown that in vitro transduction with bovine adeno-associated viral (BAAV) vectors restores connexin expression and rescues gap junction coupling in cochlear organotypic cultures from connexin-deficient mice that are models DFNB1 nonsyndromic hearing loss and deafness. The aims of this study were to manipulate inner ear connexin expression in vivo using BAAV vectors, and to identify the optimal route of vector delivery. Injection of a BAAV vector encoding a bacterial Cre recombinase via canalostomy in adult mice with floxed connexin 26 (Cx26) alleles promoted Cre/LoxP recombination, resulting in decreased Cx26 expression, decreased endocochlear potential, increased hearing thresholds, and extensive loss of outer hair cells. Injection of a BAAV vector encoding GFP-tagged Cx30 via canalostomy in P4 mice lacking connexin 30 (Cx30) promoted formation of Cx30 gap junctions at points of contacts between adjacent non-sensory cells of the cochlear sensory epithelium. Levels of exogenous Cx30 decayed over time, but were still detectable four weeks after canalostomy. Our results suggest that persistence of BAAV-mediated gene replacement in the cochlea is limited by the extensive remodeling of the organ of Corti throughout postnatal development and associated loss of non-sensory cells

Testing complete positivity

We study the modified dynamical evolution of the neutral kaon system under the condition of complete positivity. The accuracy of the data from planned future experiments is expected to be sufficiently precise to test such a hypothesis.Comment: 12 pages, latex, no figures, to appear in Mod. Phys. Lett.

Evolution of Large Scale Curvature Fluctuations During the Perturbative Decay of the Inflaton

We study the evolution of cosmological fluctuations during and after inflation driven by a scalar field coupled to a perfect fluid through afriction term. During the slow-roll regime for the scalar field, the perfect fluid is also frozen and isocurvature perturbations are generated. After the end of inflation, during the decay of the inflaton, we find that a change in the observationally relevant large scale curvature fluctuations is possible.Comment: 9 pages, 2 figures; v2: version published in PR

Influences of state anxiety on gaze behavior and stepping accuracy in older adults during adaptive locomotion

This article is available open access through the publisher’s website at the link below. Copyright © The Authors 2011.OBJECTIVES: Older adults deemed to be at a high risk of falling transfer their gaze from a stepping target earlier than their low-risk counterparts. The extent of premature gaze transfer increases with task complexity and is associated with a decline in stepping accuracy. This study tests the hypothesis that increased anxiety about upcoming obstacles is associated with (a) premature transfers of gaze toward obstacles (i.e., looking away from a target box prior to completing the step on it in order to fixate future constraints in the walkway) and (b) reduced stepping accuracy on the target in older adults. METHODS: High-risk (9) and low-risk (8) older adult participants walked a 10-m pathway containing a stepping target area followed by various arrangements of obstacles, which varied with each trial. Anxiety, eye movements, and movement kinematics were measured. RESULTS: Progressively increasing task complexity resulted in associated statistically significant increases in measures of anxiety, extent of early gaze transfer, and stepping inaccuracies in the high-risk group. DISCUSSION: These results provide evidence that increased anxiety about environmental hazards is related to suboptimal visual sampling behavior which, in turn, negatively influences stepping performance, potentially contributing to increased falls risk in older adults.Biotechnology and Biological Sciences Research Counci

EXPECTED UTILITY THEORY WITHOUT THE COMPLETENESS AXIOM*

We study axiomatically the problem of obtaining an expected utility representation for a potentially incomplete preference relation over lotteries by means of a set of von Neumann-Morgenstern utility functions. It is shown that, when the prize space is a compact metric space, a preference relation admits such a multi-utility representation provided that it satisfies the standard axioms of expected utility theory. Moreover, the representing set of utilities is unique in a well-defined sense