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Biliary tract cancers (BTCs) have poor prognosis and limited therapeutic options. The impact of O

Updates in classification of gastro-entero-pancreatic neuroendocrine neoplasms better reflect the biological characteristics of these tumours. In the present study, we analysed the characteristics of neuroendocrine tumours that could aid in a more precise stratification of risk groups. In addition, we have highlighted the importance of grade (re)assessment based on investigation of secondary tumour lesions. Two hundred and sixty-four cases of neuroendocrine tumours of gastro-entero-pancreatic origin from three centres were included in the study. Tumour morphology, mitotic count and Ki67 labelling index were evaluated in specimens of primary tumours, lymph node metastases and distant metastases. These variables were correlated with overall survival (OS) and relapse-free survival (RFS). Tumour stage, number of affected lymph nodes, presence of tumour deposits and synchronous/metachronous metastases were tested as possible prognostic features. Mitotic count, Ki-67 labelling index, primary tumour site, tumour stage, presence of tumour deposits and two or more affected lymph nodes were significant predictors of OS and RFS. At the same time, mitotic count and Ki-67 labelling index can be addressed as continuous variables determining prognosis. We observed a very high correlation between the measures of proliferative activity in primary and secondary tumour foci. The presence of isolated tumour deposits was identified as an important determinant of both RFS and OS for pancreatic (hazard ratio [HR] = 7.61, 95% confidence interval [CI] = 3.96-14.6, P < 0.0001 for RFS; HR = 3.28, 95% CI = 1.56-6.87, P = 0.0017 for OS) and ileal/jejunal neuroendocrine tumours (HR = 1.98, 95% CI = 1.25-3.13, P = 0.0036 for RFS and HR 2.59, 95% CI = 1.27-5.26, P = 0.009 for OS). The present study identifies the presence of mesenterial tumour deposits as an important prognostic factor for gastro-entero-pancreatic neuroendocrine tumours, provides evidence that proliferative parameters need to be treated as continuous variables and further supports the importance of grade determination in all available tumour foci.

A number of policy measures have been adopted to cope with ongoing ocean degradation. Marine protected areas (MPAs) are among them. MPAs and their coverage have increased worldwide, including in EU waters. Natura 2000 (Nat2000) sites are at the core of the EU biodiversity conservation strategy and have been established to protect habitats and species included in two EU directives. Besides their specific objectives, their potential to contribute to an ecosystem-wide conservation and their complementarity with other national and supranational initiatives (e.g. nationally established MPA networks, the Marine Strategy Framework Directive, the Convention on Biological Diversity Ecosystem-Based Approach) have been called into question. Using visual censuses on rocky reefs, the biomass of whole fish assemblages and of a set of ecologically important species (widely used as indicators of coastal marine ecosystem health) have been assessed to evaluate the potential ecosystem-wide effectiveness of Nat2000 marine sites located along the coasts of Sardinia (Italy). The assessment was performed in six fully protected MPAs, in 12 Nat2000 sites established or extending at sea, and in 18 adjacent unprotected control sites. Results show that the highest fish biomasses are observed in fully protected MPAs. The values observed at Nat2000 sites do not differ or only slightly differ from those observed at control sites. This shows that Nat2000 sites may not presently contribute to effectively protect fish and the related rocky reef ecosystems. These results do not dismiss at all the role of Nat2000 sites relative to the objectives for which they have been established. However, they show that to achieve ecosystem-wide benefits it is crucial to rethink and broaden the scope of Nat2000 sites and adapt their management to that. By providing sounder and more comprehensive management plans, and implementing more consistent ecosystem-wide conservation measures, Nat2000 marine sites could become an extraordinary tool at the EU scale, capable of delivering wider ecological benefits.

In this article I examine socio-environmental conflicts through the category of value. Drawing from a single case study, an industrial city in southern Italy, I address the revaluation projects underpinning the conflict around socio-ecological arrangements that are considered unfair, unsustainable and detrimental to life. Focusing on the trajectory of local environmentalism and the specific case of a women group, the paper shows how the intensification of the socio-ecological crisis prompted the shift of environmental conflicts from the sphere of production to the broader relations of social reproduction. I propose to analyse this shift through the concept of grassroots ecologies of value, which outlines a framework for thinking about how people deal with the socio-environmental contradictions in which they live, and their struggles for dignity and worth. info:eu-repo/semantics/acceptedVersion

Social insects have evolved colony behavioral, physiological and organizational adaptations (social immunity) to reduce the risks of parasitization and/or disease transmission. The collection of resin from various plants and its use in the hive as propolis, is a clear example of behavioral defense. For Apis mellifera, an increased propolis content in the hive may correspond to variations in the microbial load of the colony and to a down-regulation of an individual bee's immune response. However, many aspects of such antimicrobial mechanism still need to be clarified. Assuming that bacterial and fungal infection mechanisms differ from the action of a parasite, we studied the resin collection dynamics in Varroa destructor infested honeybee colonies. Comparative experiments involving hives with different mite infestation levels were conducted in order to assess the amount of resin collected and propolis quality within the hive, over a two year period (2014 and 2015). Our study demonstrates that when A. mellifera colonies are under stress because of Varroa infestation, an increase in the number of resin foragers is recorded, even if a general intensification of the foraging activity is not observed. A reduction in the total polyphenolic content in propolis produced in infested vs uninfested hives was also noticed. Considering that different propolis types show varying levels of inhibition against a variety of honey bee pathogens in vitro, it would be very important to study the effects against Varroa of two diverse types of propolis: from Varroa free and from Varroa infested hives. This article is protected by copyright. All rights reserved.

Aim A key paradigm of deep-sea ecology is that the ocean interior is a food-limited environment, which limits the faunal growth. Here, we estimated the efficiency of deep-sea fauna in exploiting resources to assess the potential response of deep-sea organisms to changes in the food inputs expected with global change. Location Mediterranean Sea. Time period 1989–2010. Major taxa studied Viruses, prokaryotes, meiofauna, macrofauna and megafauna. Methods Using the largest data set spanning from microbes to megafauna produced synoptically so far, we investigated patterns of abundance, biomass and ecosystem efficiency across depth-related and longitudinal gradients of food availability in both Western and Eastern Basins of the Mediterranean Sea. Results Our results revealed that prokaryotes dominated benthic biomass at depths > 2,000 m. Contrary to what has been reported at a global scale, meiofaunal biomass decreased with increasing water depth more rapidly than macrofauna and megafauna. Meiofauna showed a significant negative log-linear relationship with increasing water depth in the whole Mediterranean Sea, whereas the other benthic components, from viruses to megafauna, did not decrease significantly, decreased or even increased (e.g., prokaryotes) with increasing water depth. Taking all components together, the efficiency of benthic ecosystems in exploiting organic carbon (OC) inputs increased with increasing depth, in both mesotrophic and ultra-oligotrophic conditions of the deep Mediterranean Sea. Main conclusions Changes in ecological efficiency in exploiting the energy available in food-limited conditions suggest that deep-sea ecosystems can show a responsive adaptation to changes in OC inputs from the photic zone. Our results contribute to explaining the high efficiency of resource exploitation by consumers in limited trophic conditions and allow us to hypothesize that the consequences of a potential reduction of food supply in deep-sea ecosystems induced by global changes could be less severe than expected.

Domestic sewage is a major problem in highly urbanized coastal areas worldwide. In the present study, toxicity identification evaluation (TIE) phases I and II were applied to sediment interstitial water from 2 locations along the Sao Paulo coast in southeastern Brazil: the sewage outfalls from the city of Santos, a densely urbanized area, and the city of Bertioga, a less urbanized area. An adapted microscale sea urchin embryo-larval development bioassay was employed. Phase TIE-I manipulations were 1) ethylenediamine tetraacetic acid (EDTA) addition, 2) aeration at modified pH, 3) C18 solid-phase extraction (SPE), and 4) addition of Na2 S2 O3 . The results of the Santos TIE-I indicated toxicity by sulfides and substances with affinity to C18 resin. In Bertioga, toxicity was the result of NH3 , metals, and arsenic, as well as substances with affinity to C18 resin. Phase TIE-II aimed to specify the causes of toxicity by testing the toxicity of eluates of the sublation and C18 SPE manipulation. The results reinforced the role of both surfactants and nonpolar compounds as causative agents of toxicity in both Santos and Bertioga. Chemical analyses of sediment interstitial water or whole sediment ruled out the influence of polycyclic aromatic hydrocarbons (PAHs) or polychlorinated biphenyls (PCBs) in the toxicity of both sampling sites. Other hydrophobic substances may play a role in the toxicity of Santos and Bertioga effluents. Efforts to remove such substances from sanitary effluents must be prioritized. Environ Toxicol Chem 2017;36:1820-1832. © 2017 SETAC.

Previous works on albinism form of Asinara white donkeys (Equus asinus) identified the mutation leading to the peculiar phenotype spread to all specimens of the breed. Inbreeding naturally occurred under geographic isolation, on Asinara Island, in the Mediterranean Sea. Albino individuals can be more susceptible to develop health problems when exposed to natural sun radiation. Alternative metabolic pathways involved in photoprotection were explored in this trial. Nutrition‐related metabolites are believed to contribute to the conservation of Asinara donkeys, in which melanin, guaranteeing photoprotection, is lacking. Biochemical profiles with particular focus on blood serum β‐carotene and retinol levels were monitored. Identical natural grazing conditions for both Asinara (albino) and Sardo (pigmented) donkey breeds were assured on same natural pastures throughout the experimental period. A comparative metabolic screening, with emphasis on circulating retinol and nutrient‐related metabolites between the two breeds, was carried out over one year. Potential intra‐ and interspecimen fluctuations of metabolites involved in photoprotection were monitored, both during negative and positive photoperiods. Differences (p = .064) between blood serum concentrations of retinol from Asinara versus Sardo breed donkeys (0.630 vs. 0.490 μg/ml, respectively) were found. Retinol levels of blood serum turned out to be similar in the two groups (0.523 vs. 0.493 μg/ml, respectively, p = .051) during the negative photoperiod, but markedly differed during the positive one (0.738 vs. 0.486, respectively, p = .016). Blood serum β‐carotene levels displayed to be constantly around the limit of sensitivity in all animals of both breeds. Variations in blood serum concentrations of retinol in Asinara white donkeys can reflect the need to cope with seasonal exposure to daylight at Mediterranean latitudes, as an alternative to the lack of melanin. These results may suggest that a pulsed mobilization of retinol from body stores occurs to increase circulating levels during positive photoperiod.

Mechanisms of acquired resistance to trastuzumab-based treatment in gastric cancer are largely unknown. In this study, we analyzed 22 pairs of tumor samples taken at baseline and post-progression in patients receiving chemotherapy and trastuzumab for advanced HER2-positive [immunohistochemistry (IHC) 3+ or 2+ with in-situ hybridization (ISH) amplification] gastric or gastroesophageal cancers. Strict clinical criteria for defining acquired trastuzumab resistance were adopted. Loss of HER2 positivity and loss of HER2 over-expression were defined as post-trastuzumab IHC score

Udgivelsesdato: Juli The exponential growth of off-shore mariculture that has occurred worldwide over the last 10 years has raised concern about the impact of the waste produced by this industry on the ecological integrity of the sea bottom. Investigations into this potential source of impact on the biochemistry of the sea floor have provided contrasting results, and no compelling explanations for these discrepancies have been provided to date. To quantify the impact of fish-farm activities on the biochemistry of sediments, we have investigated the quantity and biochemical composition of sediment organic matter in four different regions in the temperate-warm Mediterranean Sea: Akrotiri Bay (Cyprus), Sounion Bay (Greece), Pachino Bay (Italy), and the Gulf of Alicante (Spain). In these four study regions, the concentrations of phytopigments, proteins, carbohydrates, and lipids in the sediments were measured, comparing locations receiving wastes from fish farms to control locations in two different habitats: seagrass beds and soft nonvegetated substrates. Downward fluxes were also measured in all of the regions, up to 200 m from the fish farms, to assess the potential spatial extent of the impact. In all four regions, with the exception of seagrass sediments in Spain, the biochemistry of the sediments showed significant differences between the control and fish-farm locations. However, the variables explaining the differences observed varied among the regions and between habitats, suggesting idiosyncratic effects of fish-farm waste on the biochemistry of sediments. These are possibly related to differences in the local physicochemical variables that could explain a significant proportion of the differences seen between the control and fish-farm locations. Biodeposition derived from the fish farms decreased with increasing distance from the fish-farm cages, but with different patterns in the four regions. Our results indicate that quantitative and qualitative changes in the organic loads of the sediments that arise from intensive aquaculture are dependent upon the ecological context and are not predictable only on the basis of fish-farm attributes and hydrodynamic regimes. Therefore, the siting of fish farms should only be allowed after a case-by-case assessment of the ecological context of the region, especially in terms of the organic matter load and its biochemical composition.

BACKGROUND Preclinical and clinical studies suggest synergistic activity between somatostatin analogues and mammalian target of rapamycin inhibitors. The activity and safety of everolimus was assessed in combination with octreotide long-acting repeatable (LAR) in patients with neuroendocrine tumors (NETs) of gastroenteropancreatic and lung origin. METHODS This was a phase 2, multicenter trial using a Simon's 2-stage minimax design. Treatment-naive patients with advanced well-differentiated NETs of gastroenteropancreatic tract and lung origin received everolimus 10 mg daily, in combination with octreotide LAR 30 mg every 28 days. The primary endpoint was objective response rate (ORR). RESULTS A total of 50 patients (median age, 60.5 years) were enrolled. Primary tumor sites were: pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum and duodenum (2 patients), and unknown (14 patients). Thirteen patients (26%) had carcinoid syndrome. Treatment-related adverse events (AEs) were mostly grade 1 or 2; the only grade 4 AE was mucositis in 1 patient, whereas grade 3 AEs included skin rash in 1 case (2%), stomatitis in 4 cases (8%), and diarrhea in 11 cases (22%). The ORR was 18%; 2% of patients had a complete response (CR), 16% a partial response (PR) and 74% achieved stable disease (SD). All CRs and all PRs as well as 92% of SDs had a duration ≥6 months. The clinical benefit (CR+PR+SD) was 92%. At a median follow-up of 277 days, median time to progression and overall survival were not reached. CONCLUSIONS The everolimus-octreotide LAR combination was active and well tolerated in these previously treated patients with advanced NETs, suggesting a possible role as first-line treatment in patients with NET. Cancer 2014;120:2457–2463. © 2014 American Cancer Society.

Aim Understanding how biodiversity varies at different spatial scales and the drivers behind these patterns is a crucial issue in ecology. This is evident for the deep sea, the largest biome of the biosphere, where there is little information available on the spatial and temporal variability of biodiversity. Here, we investigated the variability and potential drivers of species richness, turnover and functional biodiversity of deep-sea nematodes at a depth of 3000 m across different spatial scales and in two periods of contrasting pelagic productivity. Location The Mediterranean Sea. Methods We used for the first time a hierarchical sampling strategy that includes different spatial scales, from tens of metres (small scale) to hundreds of kilometres (macroscale). Results We show that the variability in biodiversity is greatest at the macroscale, although the rate of variability is about two- to three-fold lower than observed for nematode abundance. Also, turnover diversity is highest at the macroscale (and uncoupled from species richness), and significantly decreases to the meso- and local scales. Functional diversity is positively related to species richness and its variability is associated with the change in richness of predators. The drivers of spatial variability of biodiversity are different at different spatial scales. Our data identify the pivotal role of food quantity in the control of variability in biodiversity attributes at the macroscale, while the quality and bioavailability of food sources have a key role in driving beta diversity and biodiversity attributes at small spatial scales.Also, the largest variations in biodiversity attributes at both macroscales and mesoscales are related to periods of high food input from the euphotic zone.

The purpose of this study was to assess treatment margins in free-breathing irradiation of pancreatic cancer after bone alignment, and evaluate their impact on conformal radiotherapy. Fifteen patients with adenocarcinoma of the head of the pancreas underwent implantation of single fiducial marker. Intrafraction uncertainties were assessed on simulation four-dimensional computed tomography (4D CT) by calculating maximal intrafraction fiducial excursion (MIFE). In the first ten patients, after bony alignment, the position of the fiducial was identified on weekly acquired megavolt cone-beam CT (MV-CBCT). The interfraction residual uncertainties were estimated by measuring the fiducial displacements with respect to the position in the first session. Patient mean (pM) and patient standard deviation (pSD) of fiducial displacement, mean (μM) and standard deviation (μSD) of pM, and root-mean-square of pSD (σ(res)) were calculated. In the other five patients, MIFE was added to the residual component to obtain personalized margin. In these patients, conformal kidney sparing (CONKISS) irradiation was planned prescribing 54/45 Gy to PTV1/PTV2. The organ-at-risk limits were set according to current NCCN recommendation. No morbidity related to the fiducial marker implantation was recorded. In the first ten patients, along right-left, anterior-posterior, and inferior-superior directions, MIFE was variable (mean ± std = 0.24 ± 0.13 cm, 0.31 ± 0.14 cm, 0.83 ± 0.35 cm, respectively) and was at most 0.51, 0.53, and 1.56 cm, respectively. Along the same directions, μM were 0.09, -0.05, -0.05 cm, μSD were 0.30, 0.17, 0.33 cm, and σ(res) were 0.35, 0.26, and 0.30 cm, respectively. MIFE was not correlated with pM and pSD. In the five additional patients, it was possible to satisfy recommended dose limits, with the exception of slightly higher doses to small bowel. After bony alignment, the margins for target expansion can be obtained by adding personalized MIFE to the residual interfraction term. Using these margins, conformal free-breathing irradiation is a reliable option for the treatment of pancreatic cancer.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare condition that originates from dendritic cells. We report on the fi rst case of Epstein–Barr virus (EBV)-driven post-transplant lymphoproliferative disorder (PTLD) of donor origin in a BPDC patient post-allogeneic haematopoietic stem cell transplantation (HSCT). Flow cytometry study identified a cell population CD4+/CD56+/CD45RA+/CD123+/TCL1+ suggestive of BPDCN diagnosis, which was confirmed by a lymph node biopsy (cells positive for BCL11a, BDCA-2, CD2AP, CD123, TCL1 and S100). Cytogenetic analysis revealed a complex karyotype: (19 metaphase) 47,XX,t(1;6)(q21;q2?5),-13+2mar[11]/47, XX, +21 [3]/46,XX [5]. The patient was started on acute myeloid leukaemia (AML) induction schedule, and subsequently an allogeneic HSCT was performed. On day +36 post-HSCT, bone marrow biopsy/aspirate showed complete morphological remission, and chimerism study showed 100% donor chimera. However, on day +37, the patient was found to have enlarged cervical and supraclavicular lymphoadenopathy, splenomegaly and raised lactic dehydrogenase. EBV-DNA copies in blood were elevated, consistent with a lytic cycle. A lymph node biopsy showed EBV encoded RNA and large atypical B cells (CD45dim, CD4+/CD56+, monoclonal for k-chain, CD19+/CD20+/CD21+/CD22+/CD38+/CD43+/CD79b/CD5/CD10), consistent with PTLD monomorphic type. Chimerism study showed that PTLD was of donor origin. This case together with the recent literature findings on BPDCN and PTLD are discussed. Copyright © 2012 John Wiley & Sons, Ltd.

Climate changes are expected to induce significant modifications in biodiversity on the global scale, but little is known as to how biodiversity has been affected by recent changes in the deep sea. We have used nematodes to investigate the response of deep-sea biodiversity to an extensive climate anomaly that modified the physico-chemical characteristics of the deep waters of the Eastern Mediterranean. Using a decadal data set (from 1989 to 1998), we provide evidence that deep-sea nematode diversity can be strongly and rapidly affected by temperature shifts. The abrupt decrease in temperature (of about 0.4 °C) and modified physico-chemical conditions that occurred between 1992 and 1994 caused a significant decrease in nematode abundance and a significant increase in diversity. This temperature decrease also resulted in decreased functional diversity and species evenness, and in an increase in the similarity to colder deep-Atlantic fauna. When the temperature recovered (after 1994–1995), the biodiversity only partially returned to previous values. We conclude that deep-sea fauna is highly vulnerable to environmental alteration, and that deep-sea biodiversity is also significantly affected by very small temperature changes. The results presented here provide new elements towards a better understanding of the potential large-scale consequences of climate change.