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

Modeling and control of a modular iron bird

This paper describes the control architecture and the control laws of a new concept of Modular Iron Bird aimed at reproducing flight loads to test mobile aerodynamic control surface actuators for small and medium size aircraft and Unmanned Aerial Vehicles. The iron bird control system must guarantee the actuation of counteracting forces. On one side, a hydraulic actuator simulates the hinge moments acting on the mobile surface due to aerodynamic and inertial effects during flight; on the other side, the actuator to be tested applies an active hinge moment to control the angular position of the same surface. Reference aerodynamic and inertial loads are generated by a flight simulation module to reproduce more realistic conditions arising during operations. The design of the control action is based on a dynamic model of the hydraulic plant used to generate loads. This system is controlled using a Proportional Integral Derivative control algorithm tuned with an optimization algorithm taking into account the closed loop dynamics of the actuator under testing, uncertainties and disturbances in the controlled plant. Numerical simulations are presented to show the effectiveness of the proposed architecture and control laws

Rapamycin inhibits mTOR/p70S6K activation in CA3 region of the hippocampus of the rat and impairs long term memory

The present study was aimed at establishing whether the mTOR pathway and its downstream effector p70S6K in CA3 pyramidal neurons are under the modulation of the cholinergic input to trigger the formation of long term memories, similar to what we demonstrated in CA1 hippocampus. We performed in vivo behavioral experiments using the step down inhibitory avoidance test in adult Wistar rats to evaluate memory formation under different conditions. We examined the effects of rapamycin, an inhibitor of mTORC1 formation, scopolamine, a muscarinic receptor antagonist or mecamylamine, a nicotinic receptor antagonist, on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition was conducted 30 min after i.c.v. injection of rapamycin. Recall testing was performed 1h, 4h or 24h after acquisition. We found that (1) mTOR and p70S6K activation in CA3 pyramidal neurons were involved in long term memory formation; (2) rapamycin significantly inhibited mTOR and of p70S6K activation at 4h, and long term memory impairment 24h after acquisition; (3) scopolamine impaired short but not long term memory, with an early increase of mTOR/p70S6K activation at 1h followed by stabilization at longer times; (4) mecamylamine and scopolamine co-administration impaired short term memory at 1h and 4h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1h and 4h; (5) mecamylamine and scopolamine treatment did not impair long term memory formation; (6) unexpectedly, rapamycin increased mTORC2 activation in microglial cells. Our results demonstrate that in CA3 pyramidal neurons the mTOR/p70S6K pathway is under the modulation of the cholinergic system and is involved in long-term memory encoding, and are consistent with the hypothesis that the CA3 region of the hippocampus is involved in memory mechanisms based on rapid, one-trial object–place learning and recall. Furthermore, our results are in accordance with previous reports that selective molecular mechanisms underlie either short term memory, long term memory, or both. Furthermore, our discovery that administration of rapamycin increased the activation of mTORC2 in microglial cells supports a reappraisal of the beneficial/adverse effects of rapamycin administration

Advances in the study of geophysical signals from Mt. Etna volcano.

Long-period seismic signals, including LP events and tremor, observed on many volcanoes worldwide, may play a crucial role in the forecasting of volcanic eruptions as these signals are direct indicators of sub-surface magma dynamics. Their location is widely agreed to be useful for mapping the extension and geometry of the plumbing system and also for quantifying pressure transients caused by resonance or movement of fluids along the conduits. At Mt. Etna detailed investigations on these signals started systematically only after the installation of a broad-band seismic network (since 2003). Thereafter, we present the main results recently obtained on this volcano by analysing tremor, LP and VLP events during two eruptive episodes in the second half of 2007. We also discuss results of cross analysis performed between tremor and gravity sequences acquired simultaneously at Mt. Etna during the 2002-03 eruption and during the December 2005-January 2006 period of quiescence. We detected common anomalies which are indicative of a quasi-closed system, becoming progressively enriched in volatiles. These studies, carried out in the framework of the VOLUME Project, provide new insight into the shallow plumbing system of Etna and grant valuable tools for volcanic hazard forecasting and risk mitigation

A protein kinase a-independent pathway controlling aquaporin 2 trafficking as a possible cause for the syndrome of inappropriate antidiuresis associated with polycystic kidney disease 1 haploinsufficiency.

Renal water reabsorption is controlled by vasopressin (AVP) which binds to V2 receptors resulting in PKA activation, phosphorylation of AQP2 at serine 256 (pS256) and translocation to the plasma membrane. Besides S256, AVP causes dephosphorylation of S261. Recent studies showed that cyclin-dependent kinases can phosphorylate S261 AQP2 peptides in vitro. In an attempt to investigate the possible role of cdks on AQP2 phosphorylation, we identified a new PKA-independent pathway regulating AQP2 trafficking. In ex-vivo kidney slices and MDCK-AQP2 cells, R-roscovitine, a specific cdks inhibitor, increased pS256 and decreased pS261. The changes in AQP2 phosphorylation were paralleled by an increase in cell surface AQP2 expression and osmotic water permeability in the absence of forskolin stimulation. Of note, R-roscovitine didn’t alter cAMP-dependent PKA activity. Because phosphorylation results from the balance between kinase and phosphatase activity, we evaluated the possible contribution of protein phosphatases PP1, PP2A and PP2B. Of these, R-roscovitine treatment specifically reduced PP2A protein expression and activity in MDCK cells. Interestingly, in PKD1+/- mice displaying a syndrome of inappropriate antidiuresis with high level of pS256 despite unchanged AVP and cAMP, we found a reduced PP2A expression and activity and reduced pS261. Similarly to what previously found in PKD1+/- mice, R-roscovitine treatment caused a significant decrease in intracellular calcium in MDCK cells. Our data indicate that a reduced activity of PP2A, secondary to reduced intracellular Ca2+ levels, promotes AQP2 trafficking independently of the AVP-PKA axis. This pathway may be relevant for explaining pathological states characterized by inappropriate AVP secretion and positive water balance

Reply to comment by D. Carbone and D. Patanè on “Multi-disciplinary investigation on a lava fountain preceding a flank eruption: the 10 May 2008 Etna case”

Bonaccorso et al. [2011a] investigated the source and magma dynamics of the 10 May 2008 lava fountain at the South-East Crater (SEC) of Mount Etna through a multidisciplinary approach that integrated a wide data set ranging from bulk rock compositions of the erupted products to seismic tremor and long-period events, tilt and gravity signals. Using a large dataset, the study provided a robust framework in which the mechanism of the 10 May 2008 lava fountain is explained as a violent release of bubble-rich magma layer previously trapped at the top of a shallow reservoir located between −0.5 and 1.5 km above sea level (asl). This result is in agreement with recent relevant literature [Allard et al., 2005; Vergniolle and Ripepe, 2008; Aiuppa et al., 2010; Andronico and Corsaro, 2011; Bonaccorso et al., 2011b; Calvari et al., 2011; Vergniolle and Gaudemer, 2012]. In the introduction of their comment Carbone and Patanè [submitted] affirm that in their opinion the interpretation that “the lava fountain was generated by the fragmentation of a foam layer trapped at the top of shallow reservoir” is not soundly based. This comment’s conclusion is puzzling because one of the comment’s authors (D. Patanè) is also a co-author on the paper by Aiuppa et al. [2010] where the same conclusion, now criticized, was well supported (see figure 5 and conclusions of that paper). In particular, in the conclusions Aiuppa et al. [2010] reported that “The paroxysmal SEC episodes mark the violent release of a bubble-rich magma layer, with bubbles having relatively shallow reservoir ...", that is, the same conclusion now criticized in the comment. After this, the comment raises issues concerning the analysis and interpretation of gravity and tilt data in the multidisciplinary approach presented by Bonaccorso et al. [2011a]. The comment by Carbone and Patanè is divided into 4 paragraphs, labelled “1. Introduction”, “2. Gravity changes”, “3. Tilt changes” and “4. Concluding remarks” with only paragraphs 2 and 3 containing specific comments. In this reply, we address these two paragraphs, and we shall show how the assumptions underlying the comment are merely speculative and why the results presented by Bonaccorso et al.[2011a] remain valid

Circulating tumor DNA and disease recurrence in early stage breast cancer: From a case-control study to a prospective longitudinal trial

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Surface and deep strain at Mt. Etna volcano (Sicily, Italy) during the 2003-2004 inflation phase

We carried out a study of the seismicity and ground deformation occurred on Mount Etna volcano after the end of 2002-2003 eruption and before the onset of 2004-2005 eruption, and recorded by the permanent local seismic network run by Istituto Nazionale di Geofisica e Vulcanologia - Sezione di Catania and by the geodetic surveys carried out in July 2003 and July 2004 on the GPS network. We provided a description of seismicity rate and main seismic swarms which occurred during the investigated period. Mostly of the earthquakes are clustered in two main clusters located on the north-eastern (E-W aligned and above the sea level) and south-eastern (NW-SE aligned and from 3 to 8 Km below the sea level) sectors of the volcano. in order to better understand the kinematic processes of the volcano, the 3D relocation were used to compute fault plane solutions and a selected dataset was inverted to determine stress and strain tensors. The focal solutions on the north-eastern sector show clear left-lateral kinematics along an E-W fault plane, in good agreement with the Pernicana fault kinematics. The focal solutions on the south-eastern sector show a main right-lateral kinematics along a NW-SE fault plane evidencing a roughly E-W oriented compression coupled with a N-S extension. Surface ground deformation affecting Mt Etna and measured by GPS surveys highlights a marked inflation during the same period, mainly visible on the western and upper sectors of the volcano; on the contrary, its eastern side shows an exceptionally strong seawards and downwards motion with displacements ranging from 5 up to 10 cm along the coastline. The 2D geodetic strain tensor distribution was calculated on a 1.5 km spaced grid, in order to detail the strain axes orientation above the entire GPS network. The results of the 2D geodetic strain calculation evidenced the very strong extension (mainly along an- ENE-WSW axis) of the summit area that was already considered as the cause of the 2004-2005 eruption; this main ENE-WSW extension continues throughout the eastern flank, but here coupled with a WNW-ESE contraction, meaning a right-lateral shear along a NW-SE oriented fault plane. The opposite deformation of the eastern sector of the volcano, as measured by seismicity and ground deformation has to be interpreted by considering the different depths of the two signals. Seismic activity along the NW-SE alignment is, in fact, located between 3 and 8 km b.s.l. and it is then affected by the very strong additional EW compression induced by the inflating source located by inverting GPS data just westwards and at the same depth. Ground deformation measured by GPS at the surface, on the contrary, is mainly affected by the shallower dynamics of the eastern flank, fastly moving towards East that produces an opposite (extension) E-W strain. It is also meaningful, confirming the decoupling between the surface and deep strain, that all the seismicity of the south-eastern sector lies beneath the sliding plane already modeled by geodetic data for the same time interval and for the 2004-2006 period and also beneath the deeper one previously modeled during the 1993-1998 period when the eastern flank velocity was much slower

La sequenza sismica nel versante nord-occidentale dell'Etna del 19-27 Dicembre 2009 : evidenze di ricarica magmatica profonda?

E’ stata analizzata la sequenza sismica che ha interessato il versante nord-occidentale dell’Etna nel periodo 19-27 dicembre 2009 (Fig. 1). Essa è stata caratterizzata da oltre 400 scosse di magnitudo compresa tra 1.0 e 4.8, localizzate ad una profondità tra 20 e 30 km, con un rilevante rilascio energetico, come si osserva dalla distribuzione temporale del numero delle scosse e dell’energia ad esse associata nel tempo (Fig. 2). È interessante notare come l’energia rilasciata durante la sequenza risulti essere quasi il triplo dell’energia del periodo sineruttivo 2008, pur essendo pressoché uguale il numero di scosse registrate. In questo settore dell’area etnea, caratterizzato da sismicità profonda, poco frequente e di modesta energia, la modalità di rilascio sismico della sequenza in oggetto costituisce un elemento di novità. Infatti, più del 50% delle scosse si sono verificate nel corso delle prime 24 ore, come tipicamente osservato nel corso di sciami vulcanici sineruttivi. E’ importante evidenziare che nell’area etnea eventi sismici con profondità focali comprese tra i 10 e i 30 km vengono considerati dei veri e propri “markers” di attività vulcanica (e.g. Puglisi et al., 2001), in quanto si verificano abbastanza regolarmente durante i periodi intra-eruttivi e possono essere messi in relazione con i meccanismi di ricarica magmatica (e.g. Bonaccorso, 2001). Essi sono principalmente localizzati nei settori occidentale e meridionale del vulcano lungo strutture orientate NO-SE e NNO-SSE e, occasionalmente, lungo strutture orientate NE-SO (Patanè et al., 2004). Pertanto è ragionevole ipotizzare che il fenomeno oggetto del presente studio possa essere ricondotto ad una fase di ricarica profonda del sistema magmatico etneo

Instrumental seismic catalogue of Mt. Etna earthquakes (Sicily, Italy): ten years (2000-2010) of instrumental recordings

Instrumental seismic catalogues are an essential tool for the zonation of the territory and the production of seismic hazard maps. They are also a valuable instrument for detailed seismological studies regarding active volcanoes and, above all, for interpreting the magma dynamics and the evolution of eruptive phenomena. In this paper, we show the first instrumental earthquake catalogue of Mt. Etna, for the period 2000-2010, with the purpose of producing a homogeneous dataset of 10 years of seismological observations. During this period, 16,845 earthquakes have been recorded by the seismic network run by the Istituto Nazionale di Geofisica and Vulcanologia, Osservatorio Etneo, in Catania. A total of 6,330 events, corresponding to approximately 40% of all earthquakes recorded, were located by using a one-dimensional VP velocity model. The magnitude completeness of the catalogue is equal to about 1.5 for the whole period, except for some short periods in 2001 and 2002-2003 and at the end of 2009. The reliability of the data collected is supported by the good values of the main hypocentral parameters through the time. The spatial distribution of seismicity allowed the highlighting of several seismogenetic areas characterized by different seismic rates and focal depths. This seismic catalogue represents a fundamental tool for several research aiming to a better understanding of the behavior of an active volcano such as Mt. Etna