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Purpose: The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients.Patients and methods: Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm.Results: There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: pop-ulation for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 pa-tients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C.Conclusions: The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher nu-merical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles. Clinicaltrials.gov identifier: NCT02835924.(C) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

A re-assessment of spionid specimens collected from coasts around the Iberian Peninsula and initially assigned to Dispio uncinata Hartman, 1951 and Prionospio multibranchiata Berkeley, 1927 resulted in the recognition of two new species from the genera Dispio and Prionospio : Dispio glandulosa sp. nov . and Prionospio ( Minuspio ) sanmartini sp. nov . In addition, the examination of specimens collected near the type locality of P. multibranchiata led to a re-description of this species. The specimens examined do not correspond to the material collected from the Iberian Peninsula and it is unlikely that P. multibranchiata is found in northern European waters.

A new solitary species of Loxosomatidae (Entoprocta), Loxosoma discoides n. sp., is described. The specimens were found in the intertidal level of two locations in the Galician (NW Spain) coast. This new species, with “table-tennis bat” appearance, is characterised by showing large lateral wings in the calyx, which confer the singular aspect. It is the first record of this genus at the coast of the Iberian Peninsula.

Re-assessment of spionid specimens from Iberian Peninsula initially assigned to Dispio uncinata Hartman, 1951 and Streblospio benedicti Webster, 1879 led to the recognition of two new species from the spionid genera Dispio and Streblospio from coasts around the Iberian Peninsula. Dispio elegans sp. nov. is characterised by having an oblanceolate-shaped prostomium. In addition, the first two notopodial postchaetal lamellae are serrated with digitiform papillae, the anterior neuropodial lamellae are smooth; all branchiae are almost completely fused to the notopodial lamellae, but with the tips free; the notochaetae on chaetiger 1 are smooth, alimbate capillaries; the ventral chaetae located in the position of the sabre chaetae on chaetigers 1–2 are smooth, alimbate capillaries, but becoming granulated on chaetiger 3; and the middle and posterior chaetigers are granulated and reticulated. Streblospio padventralis sp. nov. is characterized by lacking dorsal papillae between the branchiae of chaetiger 1; the hooks have 4–5 pairs of small teeth; sabre chaetae are present from chaetiger 3; the pygidium has two ventral lappets; and brooding structures are present in the coelomic cavities. We suggest raising the status of Streblospio benedicti japonica Imajima, 1990 to full species level as S. japonica Imajima, 1990. A key for Streblospio species is provided.

The precise determination of dose-effect curves and the combination effect of drugs is of crucial importance in the development of new therapies for the most dreadful diseases. We have found that the current implementations of the theory of Chou et al. are not accurate enough in some circumstances and might lead to erroneous predictions of synergistic or antagonistic behaviour. We have identified the source of inaccuracies and fixed it thereby improving the accuracy of those methods. Here we explain the main features of our approach and demonstrate its higher accuracy as compared to the standard methods. Therefore, this new implementation might have a huge impact in the reliability of future research on new Combination Therapies., This work was supported by FICYT (grant GRUPIN14-121) and by the Spanish MINECO (project FIS2013-45469).

Exposed sandy beaches are widespread coastal habitats with temporal and spatial variability. O Rostro beach (Galicia, north-west Spain) was the most severely affected beach in the ‘Prestige’ oil spill (November 2002). Monitoring sampling was conducted to study macroinfaunal composition and structure after the oil spill episode. The purpose of this survey was to characterize macroinfaunal variations on the beach over a yearly scale (2003–2007) and determine the recovery period. These data are compared with the only available data collected before the spill (1995). Two zones where identified with different recovery trends: (1) supralittoral, occupied either by talitrid amphipods, oniscoidean isopods and insects; and (2) intertidal, where marine crustaceans prevailed. Beach morphodynamics partially buried the oil, which gradually reappeared and was dragged to the coast. Negative ecological effects were observed in the short term (six months after the 2002 spill) but macroinfauna apparently recovered in the following years (2004–2007), showing that macroinfaunal assemblages of this beach are resilient enough to recover after severe stress.

The suprabenthos is considered a major food resource for some fish and birds. Moreover, it plays a key role in the food chain and in nutrient regeneration in the surf zone. The aim of this study was to determine the factors that regulate this fauna and the differences between the suprabenthic groups, to study the possibility of seasonal variations and to compare these results with those of other studies conducted in Europe. A study and geographical comparison was conducted of the temporal patterns of the suprabenthos in the swash zone at two sandy beaches on the NE Atlantic coast (Altar and Ladeira beaches) in the NW of Spain. The study was carried out from September 2005 to August 2007 (24 months). To study the fauna, 60 m 2 was sampled monthly with a suprabenthic sledge, and a total of 101 species belonging to Peracarida and Decapoda were recorded. Total densities ranged from 0.42 ind·m − 2 to 178.75 ind·m − 2 . Ladeira beach showed higher densities and species richness than Altar beach, and the biocoenosis showed a different dynamic over the 24 months and between years and locations. These results indicate that there is no clear seasonality in the dynamic of suprabenthic species, although the variance of Peracarida orders was explained in diverse degree by environmental variables. The environmental models implemented explained between 27.7% and 93.8% of the faunal data, and hydrodynamic factors and daily global irradiance were selected as the best factors to explain the temporal variations.

The exposed sandy beach of Ladeira (Corrubedo Bay, NW Spain) was sampledduring seven years (2003-2009) after the Prestige oil spill(winter 2002-03), todetermine interannual variations in the macroinfaunal community in two ways:(i) through ecological indices (species richness and abundances, Shannon'sdiversityand Pielou's evenness) and (ii) through the density of the most representativespecies. A clear zonation pattern was found, consisting of two zones:(i) the supralittoral, occupied by talitrid amphipods, isopods and insects,and(ii) the intertidal, where marine crustaceans and polychaetes prevailed. Theamphipods Talitrus saltator and Talorchestia deshayesiidominated from the driftline upwards, and isopods (Eurydice spp.), polychaetes (Scolelepisspp.) andthe amphipod Pontocrates arenarius dominated the intertidal. Univariateindices remained constant throughout the study period in the supralittoral,but they varied widely in the intertidal zone. Multivariate analysis showedthat the Prestige oil spill scarcely affected the macroinfaunalcommunity structure during the study period (2003-2009) and its effect waslimited just to the first campaign (2003), six months after the Prestigeaccident.

Eighteen sandy beaches were sampled along the 1659 km of the Galician coast (NW Spain) six months after the Prestige oil-spill to study the impact of the fuel and the clean-up activities on the macroinfauna community. A transect was extended at each beach, from above the drift line to below the swash line at five sampled levels; at each level six 0.05 m2 replicates were taken to a depth of 30 cm and sieved through a 1mm mesh, and the organisms collected and preserved. Results were compared with previous data obtained using the same procedures. The macroinfauna was numerically dominated by the amphipod Pontocrates arenarius, the isopod genus Eurydice, the polychaete Scolelepis squamata, and the amphipod Talitrus saltator. As a result of the Prestige oil-spill and the clean-up activities, beach populations were reduced, with Eurydice and S. squamata as the most affected taxa.

The community structure of the macrobenthic (>1 mm) fauna of an intertidal soft-bottom estuary, the Ria de Foz (Galicia, Northwest Spain) was investigated on 99 occasions during June, September and December 1984 and March 1985. The infaunal data were subjected to classification and ordination techniques. The analyses indicated that sediment characteristics (grain size, percentage silt-clay and organic-matter content) and tidal height are the most important factors governing the distribution and abundance of the intertidal communities. Three faunal assemblages were identified and examined in terms of species dominance, constancy and fidelity. In the clean sands of the outer estuary two main assemblages were distinguished; one, corresponding to the “boreal LusitanianTellina community”, inhabited the middle and lower tidal levels; the other, typical of a biocoenosis of sands and slightly muddy mediolittoral sands, inhabited the upper tidal level. The third benthic assemblage occupied the muddy sands and mud of the inner estuary and displayed some features in common with theCardium edule-Scrobicularia community described by Thorson.