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Regional differences in climate vulnerability are particularly important in many countries with socio-ecological gradients or geographical and environmental spatial segregation. Many studies are regularly performed at the national level, but regional assessments can provide more detailed information and important insights into intra-national vulnerabilities. They require detailed information of many socio-ecological components that are often neglected at the regional scale but are meaningful and operational at national and international levels. In this work, we developed a climate vulnerability assessment (CVA) to investigate the vulnerability of demersal fisheries based on 19 indicators covering exposure, fisheries sensitivity, species sensitivity (SS) and adaptive capacity (AC) for nine coastal regions of Spain, contrasting the Mediterranean to Atlantic areas. Exposure was consistently larger in the Mediterranean than Atlantic regions, while AC showed the opposite trend. While fisheries and SS did not display a clear Atlantic-Mediterranean pattern, they were critical for capturing regional differences that have an impact on fisheries vulnerability. Our results highlight the generally higher vulnerability of Mediterranean demersal fisheries, mainly due to the lower AC and higher exposure of Mediterranean regions, while providing key regional elements for guiding national and international actions for adaptation. This study demonstrates that the spatial scale considered in the development of CVAs must recognise the spatial heterogeneity in the socio-ecological system within its unit of analysis in order to be a relevant tool for management and policy makers. [ABSTRACT FROM AUTHOR]

Ecological resilience has become a conceptual cornerstone bridging ecological processes to conservation needs. Global change is increasingly associated with local changes in environmental conditions that can cause abrupt ecosystem reorganizations attending to system‐specific resilience fluctuations with time (i.e. resilience dynamics).Here we assess resilience dynamics associated with climate‐driven ecosystems transitions, expressed as changes in the relevant contribution of species with different life‐history strategies, in two benthopelagic systems.We analysed data from 1994 to 2019 coming from a scientific bottom trawl survey in two environmentally contrasting ecosystems in the Western Mediterranean Sea—Northern Spain and Alboran Sea. Benthopelagic species were categorized according to their life‐history strategies (opportunistic, periodic and equilibrium), ecosystem functions and habitats. We implemented an Integrated Resilience Assessment (IRA) to elucidate the response mechanism of the studied ecosystems to several candidate environmental stressors and quantify the ecosystems' resilience. We demonstrate that both ecosystems responded discontinuously to changes in chlorophyll‐a concentration more than any other stressor. The response in Northern Spain indicated a more overarching regime shift than in the Alboran Sea. Opportunistic fish were unfavoured in both ecosystems in the recent periods, while invertebrate species of short life cycle were generally favoured, particularly benthic species in the Alboran Sea.The study illustrates that the resilience dynamics of the two ecosystems were mostly associated with fluctuating productivity, but subtle and long‐term effects from sea warming and fishing reduction were also discernible. Such dynamics are typical of systems with wide environmental gradient such as the Northern Spain, as well as systems with highly hydrodynamic and of biogeographical complexity such as the Alboran Sea. We stress that management should become more adaptive by utilizing the knowledge on the systems' productivity thresholds and underlying shifts to help anticipate both short‐term/less predictable events and long‐term/expected effects of climate change. [ABSTRACT FROM AUTHOR]

DNA fragmentation of cumulus cells could be used as an indicator of oocyte vitrification success as an indirect indicator of the quality of the oocyte. This study was designed to compare the DNA fragmentation of post‐mortem equine cumulus cells before or after vitrification in the absence of permeable cryoprotectant agents. Cumulus–oocyte complexes (COCs; n = 56) were recovered from slaughterhouse ovaries and subjected to in vitro maturation (42 hr/38.2°C/5%CO2) before (control group) or after a permeable cryoprotectant‐free vitrification method using 1 M sucrose (vitrification group). After in vitro maturation, COCs were denuded, and cumulus cells were washed and stored at −80°C until thawing. Cumulus cell samples were processed with the chromatin dispersion test (Ovoselect, Halotech DNA, Spain). Low, high and total DNA fragmentation percentages of cumulus cells were recorded and compared between the two groups by Student's t test. Results were expressed as mean ± SEM. The vitrified group resulted in significantly higher (p < 0.05) percentages for low (16.81 ± 1.62 vs. 6.63 ± 0.77) and total (21.14 ± 1.84 vs. 12.76 ± 1.48) DNA fragmentation of cumulus cells. There were no significant differences between groups for high DNA fragmentation of cumulus cells. In conclusion, permeable cryoprotectant‐free vitrification of equine oocytes increased the total DNA fragmentation rate of cumulus cells but protected them against high DNA fragmentation rates. Further studies are needed to examine the relationship between DNA fragmentation of cumulus cells and the developmental competence of equine oocytes. [ABSTRACT FROM AUTHOR]

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The primary objective of this phase I study of LY2780301, a dual p70 S6 kinase and Akt inhibitor, was to determine the recommended phase II dose as a single agent in patients with advanced cancer. Secondary objectives included safety, pharmacokinetic, and pharmacodynamic analyses, and co-clinical analyses in Avatar models. Eligible patients received total daily doses of LY2780301 100-500 mg, given orally as a single dose or divided into 2 doses for 28-day cycles. Dose escalation followed 3 + 3 design. The primary pharmacodynamic endpoint was inhibition of S6 assessed by skin and tumor biopsy. Thirty-two patients were treated. Common toxicities possibly related to treatment included constipation (19 %), fatigue (13 %), nausea (9 %), and diarrhea (9 %). Grade 3/4 toxicities potentially related to treatment were anemia ( n = 2), increased alanine aminotransferase/aspartate aminotransferase (ALT) ( n = 1), and increased gamma-glutamyl transpeptidase (GGT) ( n = 1). One patient experienced best overall response of prolonged stable disease for 6 cycles. Plasma exposures of LY2780301 exceeded predicted efficacious exposures, but were not dose proportional. Among patients receiving 500 mg daily >50 % exhibited reduced S6 in skin biopsies at Day 8 of treatment, but the effect was not maintained. Plasma concentrations of LY2780301 and/or its metabolites were not correlated with S6 expression in the epidermis. There was minimal antitumor activity against the model, CRC 019. Avatar models showed minimal pharmacodynamic effects consistent with the observed antitumor effects. This study suggests a dose of LY2780301 500 mg QD for future studies. [ABSTRACT FROM AUTHOR]

This phase I trial determined the recommended dose for phase II trials (RD) of carboplatin 1-h intravenous (i.v.) infusion followed by PM00104 1-h i.v. infusion on Day 1 every 3 weeks (q3wk) in adult patients with advanced solid tumors. A toxicity-guided, dose-escalation design was used. Patients were stratified and divided into heavily ( n = 6) or mildly pretreated ( n = 14) groups. Transient grade 4 thrombocytopenia (in one heavily and three mildly pretreated patients) was the only dose-limiting toxicity (DLT) observed. Carboplatin AUC3-PM00104 2.0 mg/m was the RD in both groups. At this RD, the carboplatin AUC was equal to ~60 % the target AUC used in other combinations, and the PM00104 dose intensity was 56-67 % of the value achieved at the RD for single-agent PM00104 given as 1-h infusion q3wk. Most treatment-related adverse events were grade 1/2. They mainly consisted of gastrointestinal and general symptoms, such as fatigue, anorexia, mucosal inflammation or nausea. Transient neutropenia (50 % of patients) and thrombocytopenia (33-38 %) were the most common severe hematological abnormalities; their incidence was higher than with single-agent PM00104. No pharmacokinetic drug-drug alterations occurred. Partial response was found in one patient with triple negative breast cancer pretreated with paclitaxel/bevacizumab. Three patients with colorectal cancer, head and neck cancer, and tumor of unknown origin had disease stabilization for ≥3 months. In conclusion, no optimal dose was reached due to overlapping myelosuppression despite stratification according to prior treatment. Therefore, this carboplatin plus PM00104 combination was not selected for further clinical research. [ABSTRACT FROM AUTHOR]

In 1980 and 1995, the European hake (Merluccius merluccius) population off the Balearic Islands (northwestern Mediterranean) underwent changes at both the individual level and the population level. There was a sharp decrease in abundance that coincided with a change in the seasonal catch-per-unit-effort pattern in 1980. A new population scenario emerged after 1980 characterized by an increase in the intrinsic growth rate and a decrease in carrying capacity; however, catchability remained the same. An age-structure truncation could have caused these changes, making the population more dependent on year-to-year recruitment. A change in size structure also occurred in 1995, which was evidenced by a sudden decrease in the mean length-at-age (L) and abundance of recruits and a change in the density-dependent effect on recruits. As the Mediterranean trawl fishery mainly harvests recruits and juveniles and fishery harvesting induces adaptive changes in life history traits, the sharp decrease in L of recruits could be explained as a growth reduction due to the selective pressure to stay under mesh size for longer and thus maximize survival until reproduction. These individual and population transitions explain the changes in the response to the environmental forcing observed in the European hake off the Balearic Islands. [ABSTRACT FROM AUTHOR]

KRAS mutation testing has become part of standard colorectal cancer (CRC) management. There is a pressing need to establish standardized preanalytical (or prePCR) parameters, which would allow for current and future analytical and postnalytical phases to be reproducible across different platforms and laboratories. As the Spanish national reference center, we submit our experience in the study of KRAS mutations. We present a realistic approach for the preanalytical phase of KRAS testing in CRC. Although there are inconsistencies in how pathologists participate in KRAS testing, this protocol can easily be implemented in pathology laboratories worldwide, since control over the morphology of the specimen is maintained throughout the procedure. [ABSTRACT FROM AUTHOR]

Abstract: Short spatio–temporal variations in the feeding intensity and the diet of the European hake, Merluccius merluccius, together with the abundance of their potential prey were studied between August 2003 and June 2004 at two locations, northwest (Sóller) and south (Cabrera), off the island of Mallorca (Balearic Islands, Western Mediterranean) at depths between 150 and 750m. The two areas present different oceanographic conditions. Hake was mainly distributed along the shelf-slope break and the upper slope (between 166 and 350m) where recruits (TL<18cm) were dominant. The hake''s diet varied as a function of size. Recruits fed mainly on micronektonic prey, and the diet was influenced primarily by seasonality, with two dietary patterns (identified by MDS analyses) corresponding to August–September 2003 (summer) and to November 2003/February–April 2004 (autumn–winter). The summer pattern was consistent with a thermally stratified water column, while November and April were consistent with homogenized temperature and salinity throughout all the water column. The main prey of recruits were the euphausiid Meganyctiphanes norvegica and the midwater fish Maurolicus muelleri in autumn–winter and myctophids (mainly Ceratoscopelus maderensis) in summer. In contrast to recruits, the geographic factor (NW vs. S) was the main factor influencing the diets of post-recruits (TL between 18 and 21.9cm) and adults (TL⩾22cm). Hake recruits (and to a lesser extent post-recruits) and their preferred prey occupied different depth ranges during daylight periods. Meganyctiphanes norvegica and Ceratoscopelus maderensis were, for instance, distributed as much as 500m deeper than hake that had eaten them. All these trends were especially obvious at NW, an area with a more abrupt slope and with a greater influence by northern winter intermediate water (WIW) inflow in early spring than the S area. These factors probably enhanced micronekton aggregation in April, when feeding intensity (stomach fullness) increased among recruits and post-recruits only at NW. All these factors may have a crucial role in the diet, distribution and probably recruitment success of small hake. Biological factors were also important in trophic shifts in the diet and feeding of hake. Multi-linear regression models pointed to a trend of higher fullness with higher hepato-somatic index (HSI). Therefore greater food consumption by hake may enhance its metabolic condition. Within the framework of shelf-break and slope ecology, we show how the ‘boundary’ mesopelagic community inhabiting the middle slope sustains the trophic requirements of hake, a species distributed at shallower depths along the shelf-slope break. Mesopelagic euphausiids and myctophids are often found in the diets of shelf-break fish. Because the boundary mesopelagic community is distributed worldwide, the high levels of fish biomass often found at shelf-slope breaks could be sustained trophically by deeper, offshore mesopelagic communities, an inverse energy transfer from deep to shallow-water marine ecosystems. [Copyright &y& Elsevier]

Abstract: This study evaluates the link between the recruitment process of European hake (Merluccius merluccius L.) of the Balearic Islands (western Mediterranean) and the environmental and physiological conditions. Spatio-temporal variation of abundance and condition of fish were evaluated at two locations each with different oceanographic conditions, one in the north (Sóller, SO) and another in the south (Cabrera, CA) of Mallorca Island. Environmental variables explored were hydrography, sediment characteristics, phytoplankton pigment concentration (ppc) and the trophic resources of hake. Individuals were divided in three life stages: recruits, post-recruits and young adults. Hepatosomatic index (HSI), relative condition index (Kn), gonadosomatic index (GSI) and fullness index (FI) were analysed for the three life stages. Recruitment starts in February with the incorporation of smaller hakes, and it can be followed through spring and early summer with a peak in April. However, some spatial heterogeneity in the recruitment process has been found between north and south of the Island. The main pulse of recruitment occurred at a different time in the two areas. Spatial heterogeneity was also consistent with the condition of hake recruits, with higher values of Kn and HSI at SO than at CA. Maximum values of Kn were found in February at SO and in April at CA, coinciding with the start of the different recruitment pulses to the fishing grounds. Post-recruits and young adults also showed higher condition at SO than at CA. The arrival in spring of the Western Winter Intermediate Waters (WIW) drives the spatial-temporal variation in abundance and condition of hake. Ppc was highly correlated with recruit abundance with a time lag of two months, while for post-recruits the time lag was three months. The observed differences in the condition of hake between areas could be a consequence of the fact that the waters to the north of Mallorca are comparatively more under the seasonal influence of WIW which is formed in more productive areas. Thus, this study characterises the short temporal and spatial variability in the hake recruitment process off the Balearic Islands, both in terms of abundance and fish condition. This pattern is explained on the basis of the mesoscale environmental variability observed between north and south of Mallorca and the ecological adaptive strategy of recruiting in the optimal environmental season. [Copyright &y& Elsevier]

Abstract: The spatial and temporal variations of deep-sea megafaunal assemblages from the western Mediterranean are analysed in the present paper. The assemblages from two locations of the Balearic Islands situated 120 km apart were compared using data collected seasonally on a bathymetric stratum covering the 150–750 m depth range during six bottom-trawl surveys. The assemblage structure, in terms of species composition, species dominance and population sizes, was differentially affected by the spatio-temporal variables analysed (depth, location and fishing period). Although depth was the main factor determining the assemblage composition, the differences obtained between the two locations were also relevant. On the upper slope these between-location differences in the dynamics of megafaunal assemblages were found to be related to the effect of fishing exploitation. Population size-based metrics and biomass spectra were good predictors of meso-scale fishing effects, and were mainly reflected by elasmobranchs and demersal teleosts. Nevertheless, the effects of fishing depended on the species considered. Two dominant large-sized fish species found on the upper slope in both localities, Galeus melastomus and Phycis blennoides, had higher biomass values associated with lower fishing effort. Although the mean body weight (MBW) of both species and also the mean maximum body weight (MMBW) of G. melastomus agreed with this pattern, the P. blennoides MMBW did not. This last case could be indicative of natural size-trends such as the bigger–deeper phenomenon which refers to the displacement of large individuals towards the deeper limit of their bathymetric distribution, beyond the maximum depth sampled in this study for this species. By contrast, the target species of the upper slope fishery, the red shrimp Aristeus antennatus, was not negatively affected by the direct impact of fishing activity and other environmental factors, such as the presence of specific water masses could also be important. [Copyright &y& Elsevier]

The Blackspot seabream (Pagellus bogaraveo) is a commercially appreciated demersal fish, widespread in the north-eastern Atlantic and middle-western Mediterranean. The Strait of Gibraltar (SoG) is an important fishing area where artisanal fleets from Spain and Morocco target this species using special longline gears known as "voracera". Different studies on the health status of this species claim an overexploitation of the resource without any kind of objective management measures implemented yet by the associated countries. Improving the knowledge of the population dynamics, and particularly during the spawning window, is crucial for a better management of the fishing effort for this species. There is an agreement in literature in considering the SoG as an especially energetic and dispersive spawning zone for this species. Once spawned, eggs and larvae (ELS) are assumed to be scattered by the currents towards both sides of the SoG, mostly to the eastwards Alboran basin, where high concentrations of juveniles occur.A high resolution hydrodynamic model coupled to a Lagrangian particle tracking system is employed to assess the potential dispersal pathways of blackspot seabream ELS spawned in the SoG. Recursive releases of passive tracers in different virtual spawning spots and depths within the SoG region are tracked under different tidal conditions in order to obtain an overall characterization of the spatial dispersion patterns of the studied species. Semidiurnal tidal currents emerge as the primary factor in determining the horizontal dispersion and pathway of the spawning products, although the spring-neap tidal cycle and the spawning depth can be also important variables depending on the region considered as well as the arrival zone for the ELS dispersal paths over the Alboran Sea. [ABSTRACT FROM AUTHOR]

DNA fragmentation of granulosa cells might be related to developmental competence of the equine oocyte. Granulosa cells are commonly stored before DNA fragmentation assessment, but the effect of preservation methods on this parameter remains unexplored. The aim of this study was to evaluate whether or not cryopreservation of granulosa cells affects the DNA damage. Equine oocytes were recovered from postmortem ovaries of five mares. Granulosa cells were washed by centrifugation and then analyzed (control) or stored in cryovials following four different protocols: P1 = directly plunged in liquid nitrogen (LN 2 ) and then stored at -80°C; P2 = LN 2 /-80°C adding cryoprotectants (7.5% ethylene glycol + 7.5% dimethyl sulfoxide); P3 = -80°C; P4 = -80°C + cryoprotectants. Granulosa cell samples were processed with the prototype D3-Ovoselect, Halotech DNA, Spain), and DNA was visualized under fluorescence microscopy. High, low, and total DNA fragmentation percentages were compared among treatments by analysis of variance. Results were expressed as mean ± standard error. No significant differences (P > .05) were found among treatments and the control group. Therefore, the four conservation protocols could be considered equally efficient for DNA preservation of granulosa cells from mare oocytes. In conclusion, cryopreservation of granulosa cells in any of the four protocols used adequately preserved the DNA for further analysis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: To study the HER2 gene amplification or overexpression in patients with advanced gastric cancer (GC) and their association with patient characteristics and patient survival., Patients and Methods: Tumour tissue samples from 148 patients with advanced GC were studied for HER2 by immunohistochemistry (IHC), fluorescence in situ hybridisation (FISH) and dual colour silver enhanced in situ hybridisation (dc-SISH) methods. Clinicopathological data from all patients were collected. Progression free survival and overall survival were also analysed., Results: Mean age was 67 (33-83) years; 75% were male subjects, and 51% had intestinal histological type. HER2+ rates were 10.1% (15/148) by IHC, 18.2% (27/148) by FISH+ or 21.6% (32/148) by dc-SISH+. There were significant differences in HER2+ rates according to histological type when FISH (intestinal, 23%; no intestinal, 4%; p<0.0001) or dc-SISH (intestinal, 26%; no intestinal, 6%; p<0.0001) amplification techniques were used. Median overall survival was significantly longer in HER2+ patients despite the determination technique used: IHC (21.4 vs 9.8 months, HR 0.42; p=0.005); FISH (19.6 vs 9.7 months, HR 0.49; p=0.007) or dc-SISH (19.6 vs 9.7 months, HR 0.53; p=0.009). Factors associated with favourable survival in the multivariate analysis were intestinal type and Her2+ determination by IHC, FISH or dc-SISH., Conclusion: HER2 gene amplification is significantly associated with patient survival. HER2 gene amplification approaches might be an optimal HER2/neu testing strategy for the selection of HER2+ GC patients who are candidates to be treated with anti-HER2 therapies.

This work used semen samples collected from 12 stallions and assessed for sperm morphometry by the Sperm Class Analyzer (SCA) computer-assisted system. A discriminant analysis was performed on the morphometric data from that sperm to obtain a classification matrix for sperm head shape. Thereafter, we defined six types of sperm head shape. Classification of sperm head by this method obtained a globally correct assignment of 90.1%. Moreover, significant differences (p<0.05) were found between animals for all the sperm head morphometric parameters assessed.