L19-IL2 immunocytokine in combination with the anti-syndecan-1 46F2SIP antibody format: A new targeted treatment approach in an ovarian carcinoma model

Epithelial ovarian cancer (EOC) is the fifth most common cancer affecting the female population. At present, different targeted treatment approaches may improve currently employed therapies leading either to the delay of tumor recurrence or to disease stabilization. In this study we show that syndecan-1 (SDC1) and tumor angiogenic-associated B-fibronectin isoform (B-FN) are involved in EOC progression and we describe the prominent role of SDC1 in the vasculogenic mimicry (VM) process. We also investigate a possible employment of L19-IL2, an immunocytokine specific for B-FN, and anti-SDC1 46F2SIP (small immuno protein) antibody in combination therapy in a human ovarian carcinoma model. A tumor growth reduction of 78% was obtained in the 46F2SIP/L19-IL2-treated group compared to the control group. We observed that combined treatment was effective in modulation of epithelial-mesenchymal transition (EMT) markers, loss of stemness properties of tumor cells, and in alleviating hypoxia. These effects correlated with reduction of VM structures in tumors from treated mice. Interestingly, the improved pericyte coverage in vascular structures suggested that combined therapy could be efficacious in induction of vessel normalization. These data could pave the way for a possible use of L19-IL2 combined with 46F2SIP antibody as a novel therapeutic strategy in EOC

Protocol for a 1-year prospective, longitudinal cohort study of patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy: the BARI-LIFESTYLE observational study

INTRODUCTION: Roux-en-Y gastric bypass and sleeve gastrectomy are the two most common bariatric surgery performed in the UK that result in comparable weight loss and remission of obesity-associated comorbidities. However, there is a paucity of studies examining the impact of these procedures on body composition, physical activity levels, sedentary behaviour, physical function and strength, dietary intake, health-related quality of life and costs. METHODS AND ANALYSIS: The BARI-LIFESTYLE observational study is a 1-year prospective, longitudinal cohort study within a real-world routine clinical care setting aiming to recruit 100 patients with severe obesity undergoing either primary Roux-en-Y gastric bypass or sleeve gastrectomy from two bariatric centres in London, UK. Participants will be followed up four times during the study period; presurgery baseline (T0) and at 3 (T1), 6 (T2) and 12 months (T3) postsurgery. In addition to the standard follow-up investigations, assessments including dual-energy X-ray absorptiometry scan, bioelectric impedance analysis, 6 min walk test, sit-to-stand test and handgrip test will be undertaken together with completion of questionnaires. Physical activity levels and sedentary behaviour will be assessed using accelerometer, and dietary intake will be recorded using a 3-day food diary. Outcome measures will include body weight, body fat mass, lean muscle mass, bone mineral density, physical activity levels, sedentary behaviour, physical function and strength, dietary intake, health-related quality of life, remission of comorbidities, healthcare resource utilisation and costs. ETHICS AND DISSEMINATION: This study has been reviewed and given a favourable ethical opinion by London-Dulwich Research Ethics Committee (17/LO/0950). The results will be presented to stakeholder groups locally, nationally and internationally and published in peer-reviewed medical journals. The lay-person summary of the findings will be published on the Centre for Obesity Research, University College London website (http://www.ucl.ac.uk/obesity)

Multidisciplinary analysis of 3D seismotectonic modelling: a case study of Serre and Cittanova faults in the southern Calabrian Arc (Italy)

Active normal faulting and uplifting, consistent with a WNW-ESE-oriented regional extension, dominate the Quaternary tectonics of the southern Calabrian Arc. The main tectonic structures of this extensional domain are considered to be the source of numerous historical and recent strong earthquakes, among which the 1783 seismic sequence (M 6.5–7) was one of the most destructive earthquakes ever recorded in Southern Italy. Previous works on the seismotectonic of the Calabrian Arc indicate a disagreement on the attitude (E-dipping vs W-dipping) of the main seismogenic sources slicing across southern Calabria, whereby the seismotectonic framework is still debated. Following a multidisciplinary approach, based on morpho-structural and seismological data, the geometry at depth of the most reliable sources (i.e., Cittanova and Serre faults) was first modelled in a 3D environment to retrieve information about their seismic potential. The GNSS data from the permanent stations of RING/RDN and TopNETlive Italy networks have been processed in order to estimate the velocity field affecting this area. Then, data inversion allowed us to document a predominant WNW-ESE active extensional strain orthogonally to the modelled faults, consistent with the regional dynamics. The reliability of the model was tested using empirical relationships and fault response modelling simulation. Furthermore, slip tendency analysis revealed the propensity to slip of the modelled planes by applying a remote stress state derived from the kinematic-structural survey on fault planes

Brief communication: Co-seismic displacement on 26 and 30 October 2016 ( M w = 5.9 and 6.5) – earthquakes in central Italy from the analysis of a local GNSS network

Abstract. On 24 August 2016 a strong earthquake (Mw = 6.0) affected central Italy and an intense seismic sequence started. Field observations, DInSAR (Differential INterferometry Synthetic-Aperture Radar) analyses and preliminary focal mechanisms, as well as the distribution of aftershocks, suggested the reactivation of the northern sector of the Laga fault, the southern part of which was already rebooted during the 2009 L'Aquila sequence, and of the southern segment of the Mt Vettore fault system (MVFS). Based on this preliminary information and following the stress-triggering concept (Stein, 1999; Steacy et al., 2005), we tentatively identified a potential fault zone that is very vulnerable to future seismic events just north of the earlier epicentral area. Accordingly, we planned a local geodetic network consisting of five new GNSS (Global Navigation Satellite System) stations located a few kilometres away from both sides of the MVFS. This network was devoted to working out, at least partially but in some detail, the possible northward propagation of the crustal network ruptures. The building of the stations and a first set of measurements were carried out during a first campaign (30 September and 2 October 2016). On 26 October 2016, immediately north of the epicentral area of the 24 August event, another earthquake (Mw = 5.9) occurred, followed 4 days later (30 October) by the main shock (Mw = 6.5) of the whole 2016 summer–autumn seismic sequence. Our local geodetic network was fully affected by the new events and therefore we performed a second campaign soon after (11–13 November 2016). In this brief note, we provide the results of our geodetic measurements that registered the co-seismic and immediately post-seismic deformation of the two major October shocks, documenting in some detail the surface deformation close to the fault trace. We also compare our results with the available surface deformation field of the broader area, obtained on the basis of the DInSAR technique, and show an overall good fit

GEOLOGIA DE LAS MARGENES DE LA PLACA DEL CARIBE: GENERALIDADES EN GUATEMALA, COSTA RICA, LA ESPAÑOLA Y RESULTADOS PRELIMINARES DEL ANALISIS DE UNA TRANSVERSAL EN LA CORDILLERA DE LA COSTA DE VENEZUELA

The Caribbean Plate margins are constituted by deformed belts built up since the Cretaceous in acompressional and strike-slip stress field, which allowed overthrusting of the Caribbean crust onto the Pacific,North and South American Plates.The Caribbean borders include Jurassic-Cretaceous ophiolitic units (Great Antilles, Venezuela, Costa Rica,Guatemala, etc.), composed by mantle peridotites, gabbros, volcanic and sedimentary covers, which have beendeformed in at least two ductile penetrative phases and were often metamorphosed in the prehnite-pumpelleyite,green and blue schist, amphibolite, and in places eclogite facies. These units may present part of a subductioncomplex or are an accretionary prism.This paper deals with a regional geological survey (1989-1993) conducted on the main periCaribbean ophioliticunits of Guatemala, Costa Rica, Hispanola, and Venezuela. The preliminary data, recently updated with new anddetailed researches, allow to recognize the magmatic affinities (MORB and IAT) of the different reconstructedlithological sequences, which can be related with an hypothetical kinematic model of the development of theCaribbean Plate. Los márgenes de la placa del Caribe están constituidos por cinturones deformados debido a una seriede fases compresivas ocurridas desde el Cretácico, con esfuerzos tensionales y/o fallas transcurrentes super-puestos. Estos cinturones deformados contienen porciones variables de corteza caribeña sobrecorrida a las placasadyacentes (Norte y Suramericana, Pacífica).En las Antillas Mayores, Venezuela, Costa Rica y Guatemala se conocen unidades ofiolíticas de edad Jurásica-Cretácica, constituidas por secuencias de manto, corteza y una cubierta sedimentaria más o menos espesa; lassecuencias se encuentran generalmente serpentinizadas, deformadas en al menos dos fases dúctiles penetrativas ymetamorfizadas en las facies prehnita-pumpellita, esquistos azules y esquistos verdes.Desde el punto de vista tectónico-cinemático es posible incluir estas unidades en porciones de complejos de sub-ducción construidos por accreción o "underplating".En el presente estudio regional sobre las principales unidades ofiolíticas de los márgenes del Caribe, se eviden cian diferentes secuencias litológicas pertenecientes a procesos evolutivos con diferentes tendencias, desde MORB a IAT.Los resultados preliminares de una transversal en la Cordillera de la Costa de Venezuela permiten interpretar algunas secuencias litológicas como provenientes de protolitos tipo MOR