The Convention on Biological Diversity (CBD) and the European Union have set a target of restoring 15% of degraded ecosystems by 2020 with the aim of conserving biodiversity and enhancing the supply ...of ecosystem services. This target must be implemented alongside other similar targets aimed at reducing the number of threatened habitat and species as assessed under the Birds and Habitats directives. However, there are several uncertainties associated with achieving these targets including the benefits of restoring biodiversity and ecosystem services, the contribution required from member states and the effect of different restoration scenarios on target achievement. In this study, we evaluate options that exist for meeting an EU‐wide 15% restoration target while conserving habitats and species and enhancing ecosystem services. We explored the effects of different restoration scenarios on the percentage of threatened habitat and species secured. Lastly, we explored the effects of including financial cost into the prioritization procedure. Focusing restoration efforts on habitats with inadequate conservation status in the reporting of the Habitats Directive provides the largest benefit for species and ecosystem services. If the restoration target is set at 10% for habitat and species with inadequate or most threatened conservation status, and at 2% for all ecosystem services, about 18% of EU ecosystems should be restored to meet these targets. When the target is set at 15% of habitat and species and 3% of all ecosystem services, results showed that France hosts the highest percentage of identified priority areas (13%) followed by Spain and Finland with about 11% and Sweden with 9%. However, these numbers change when financial cost is included alongside other criteria, with France containing 35% of all areas identified. Synthesis and applications. These results suggest that to achieve the greatest benefits, funding for restoration should be directed towards habitats with inadequate conservation status rather than to species. Countries with larger areas of threatened habitat and lower restoration costs may offer better opportunities to meet targets, but including cost at the EU level may result in unequal burden sharing among countries.
Neoadjuvant chemotherapy (NACT) has been recognized as a reliable therapeutic strategy in patients with unresectable advanced epithelial ovarian cancer (EOC). The molecular events leading to platinum ...(Pt) response in NACT settings have hitherto not been explored. In the present work, longitudinal changes of miRNA expression profile were investigated to identify miRNA families with prognostic role in high-grade serous EOC patients who received the NACT regimen.
One hundred sixty-four matched tumor biopsies taken at initial laparoscopic evaluation and at interval-debulking surgery (IDS) after four courses of Pt-based therapy were selected from 82 stage IIIC–IV high-grade serous-EOC patients that were judged unsuitable for complete primary debulking and subjected the NACT protocol. miRNA profiling by microarray, real-time PCR and immuno-histochemical staining for Smad2 phosphorylation (P-Smad2) were used for data analysis.
Analysis revealed that 369 miRNAs were differentially expressed in matched biopsies (referred to as DEMs). DEMs were not scattered across the genome, but clustered into families: miR-199, let-7, miR-30, miR-181 and miR-29. Multivariate analysis showed that miR-199a-3p, miR-199a-5p, miR-181a-5p and let-7g-5p associated with overall and progression-free survival (P < 0.05); miR-199a-3p, miR-199a-5p and miR-181a-5p associated with residual tumor volume and Pt-free interval (P < 0.05). Immuno-histochemical staining confirmed an enrichment of P-Smad2, a marker of transforming growth factor-&bgr; activation, in tumors from patients with shorter PFS and OS, and with high levels of expression of miR-181a-5p (P < 0.05). Kaplan–Meier curves plotting concomitant expression of P-Smad2 and miR-181a-5p show significant differences in PFS and OS compared with those depicting the expression of each biomarker alone (P < 0.001).
This study describes several miRNA families with a prognostic role in the NACT setting. It also confirms that concomitant analysis of P-Smad2 and miR-181a-5p in surgical samples may be capable of identifying those ovarian cancer patients with poor outcome and little chance of response to Pt-based NACT.
The majority of patients with stage III–IV epithelial ovarian cancer (EOC) relapse after initially responding to platinum-based chemotherapy, and develop resistance. The genomic features involved in ...drug resistance are unknown. To unravel some of these features, we investigated the mutational profile of genes involved in pathways related to drug sensitivity in a cohort of matched tumors obtained at first surgery (Ft-S) and second surgery (Sd-S).
Matched biopsies (33) taken at Ft-S and Sd-S were selected from the ‘Pandora’ tumor tissue collection. DNA libraries for 65 genes were generated using the TruSeq Custom Amplicon kit and sequenced on MiSeq (Illumina). Data were analyzed using a high-performance cluster computing platform (Cloud4CARE project) and independently validated.
A total of 2270 somatic mutations were identified (89.85% base substitutions 8.19% indels, and 1.92% unknown). Homologous recombination (HR) genes and TP53 were mutated in the majority of Ft-S, while ATM, ATR, TOP2A and TOP2B were mutated in the entire dataset. Only 2% of mutations were conserved between matched Ft-S and Sd-S. Mutations detected at second surgery clustered patients in two groups characterized by different mutational profiles in genes associated with HR, PI3K, miRNA biogenesis and signal transduction.
There was a low level of concordance between Ft-S and Sd-S in terms of mutations in genes involved in key processes of tumor growth and drug resistance. This result suggests the importance of future longitudinal analyses to improve the clinical management of relapsed EOC.
•A spatially explicit assessment of eleven ecosystem services and one dis-service across the European Union (EU).•Three bundles of ecosystem services related to climate and land use intensity were ...identified.•Ecosystem service diversity and multifunctionality are strongly variable across EU.
We present an assessment of the spatial pattern of ecosystem services (ES) associations across Europe based on models of eleven ES and one dis-service, mapped at the extent of twenty-seven Member States of the European Union (EU27) on a 1km2 grid. We isolated three clusters of cells sharing common features in multi-ES supply associated with the main land-use-land-cover types such as forests and agricultural lands. Confronting these spatial patterns with biophysical and socio-economic drivers revealed two strong gradients structuring European ES bundles, climate and land use intensity. Variations in the diversity of ES bundles provided across administrative units (NUTS 2), quantified by the Shannon diversity index, tend to be higher in forested regions (e.g. SE Romania) and in the mosaic landscapes in the central EU27 (from eastern France to Austria). Lower diversity prevails in areas of homogeneous terrain and land use in north-western Europe (e.g. Western France). Our findings illustrate that ES trade-offs and bundles cannot be reduced to land use conflicts but also depend on climate and, for a specific bundle, to biodiversity.
Clinical and pathological parameters of patients with epithelial ovarian cancer (EOC) do not thoroughly predict patients' outcome. Despite the good outcome of stage I EOC compared with that of stages ...III and IV, the risk assessment and treatments are almost the same. However, only 20% of stage I EOC cases relapse and die, meaning that only a proportion of patients need intensive treatment and closer follow-up. Thus, the identification of cell mechanisms that could improve outcome prediction and rationalize therapeutic options is an urgent need in the clinical practice.
We have gathered together 203 patients with stage I EOC diagnosis, from whom snap-frozen tumor biopsies were available at the time of primary surgery before any treatment. Patients, with a median follow-up of 7 years, were stratified into a training set and a validation set.
Integrated analysis of miRNA and gene expression profiles allowed to identify a prognostic cell pathway, composed of 16 miRNAs and 10 genes, wiring the cell cycle, ‘Activins/Inhibins’ and ‘Hedgehog’ signaling pathways. Once validated by an independent technique, all the elements of the circuit resulted associated with overall survival (OS) and progression-free survival (PFS), in both univariate and multivariate models. For each patient, the circuit expressions have been translated into an activation state index (integrated signature classifier, ISC), used to stratify patients into classes of risk. This prediction reaches the 89.7% of sensitivity and 96.6% of specificity for the detection of PFS events. The prognostic value was then confirmed in the external independent validation set in which the PFS events are predicted with 75% sensitivity and 94.7% specificity. Moreover, the ISC shows higher classification performance than conventional clinical classifiers. Thus, the identified circuit enhances the understanding of the molecular mechanisms lagging behind stage I EOC and the ISC improves our capabilities to assess, at the time of diagnosis, the patient risk of relapse.
This study was designed to investigate the mode of action of trabectedin in myelomonocytic leukemia cells by applying systems biology approaches to mine gene expression profiling data and ...pharmacological assessment of the cellular effects. Significant enrichment was found in regulons of target genes inferred for specific transcription factors, among which MAFB was the most upregulated after treatment and was central in the transcriptional network likely to be relevant for the specific therapeutic effects of trabectedin against myelomonocytic cells. Using the Connectivity Map, similarity among transcriptional signatures elicited by treatment with different compounds was investigated, showing a high degree of similarity between transcriptional signatures of trabectedin and those of the topoisomerase I inhibitor, irinotecan, and an anti-dopaminergic antagonist, thioridazine. The study highlights the potential importance of systems biology approaches to generate new hypotheses that are experimentally testable to define the specificity of the mechanism of action of drugs.
Fiber-reinforced composites (FRC) could be feasible materials for fracture fixation devices if the mechanical properties of the composites are congruent with the local structural properties of bone. ...In a recently developed FRC implant, bisphenol A dimethacrylate (BisGMA) and triethylene glycol dimethacrylate (TEGDMA) resin was reinforced with unidirectional E-glass fibers. The addition of a braided glass fiber sleeving to the unidirectional fibers increased the torsional strength (99.5MPa) of the FRC implants at the expense of the flexural strength (602.0MPa). The flexural modulus was 15.3GPa. Two types of FRC intramedullary nails were prepared; first type was FRC as such, second type was FRC with a surface layer of bioactive glass (BG) granules. Experimental oblong subtrochanteric defect was created in 14 rabbits. The defect, which reduced the torsional strength of the bones by 66%, was fixed with an FRC intramedullary nail of either type. The contralateral intact femur served as the control. This model simulated surgical stabilization of bone metastasis. After 12 weeks of follow-up, the femurs were harvested and analyzed by torsional testing, micro-CT and hard tissue histology. Healed undisplaced peri-implant fractures were noticed in half of the animals irrespective of the type of FRC implant. Torsional testing showed no significant differences between the implantation groups. The torsional strength of the bones stabilized by either type of FRC implant was 83% of that of the contralateral femurs. In histological analysis, no implant debris and no adverse tissue reactions were observed. While the mechanical properties of the modified FRCs were suboptimal, the FRC intramedullary nails supported the femurs without structural failure, even in the cases of peri-implant fractures.
Large‐scale biodiversity monitoring is essential for assessing biodiversity trends, yet traditional surveying methods are limited in the spatial/temporal scale they can cover. Recent technological ...developments have led to computer vision‐based species identification tools, such as the Pl@ntNet application. Increasing accuracy of such algorithms presents an opportunity of integrating computer vision into larger monitoring schemes and could lead to automating ground‐based evidence provision related to agri‐environmental measures (e.g. flower strips, field margins). However, images from surveys or farmer declarations do not live up to the standards of current applications. In order to integrate these automated methods into biodiversity monitoring, more generalized models are needed.
We create a dataset using 500 manually delineated images of vegetation patches in European grasslands taken during the Land Use/cover Area Survey (LUCAS) grassland module. We train the Faster R‐CNN model to detect and extract individual flower objects. Using this model, we extract the abundance of flowers in an image, analyse their colour distribution, and use the Pl@ntNet application to identify the species of the individual flowers detected.
The best model reaches precision and recall of 0.89/0.61 and predicts 1377 flowers on the 100 test images distributed between 10 colours. Using Pl@ntNet, only 52 flowers were identified with a certainty score above 0.5 due to the limitations in image size and quality. Of these flowers, 30% were correctly automatically identified at the species level and 42% at the genus level.
The results show that we can automatically extract valuable information on floral abundances, colours, and sizes from images of vegetation patches, though in most cases better images are needed for species identification. Despite limitations with image quality, integrating this workflow into large‐scale monitoring could speed up the sampling process and allow for better spatial and temporal data on floral diversity and abundance.
Large scale biodiversity monitoring is essential for assessing biodiversity trends, yet traditional surveying methods are limited in the spatial/temporal scale they can cover. We trained a model with a dataset using 500 manually delineated images of vegetation patches in European grasslands which was able to automatically extract valuable information on floral abundances, colours and sizes.
•It is possible to relate agri-environmental efforts to nature value indicators.•Spatial econometrics can be used to evaluate the impact of rural development measures on nature value indicators.•Not ...accounting for the spatial effects of rural development measures leads to severe biases.•Delayed effects over time are observed as regards the impact of rural development measures on nature value indicators.•Spatial resolution does matter since the impacts of policy measures differ according to the scale of the analysis.
This paper proposes an approach for assessing the effectiveness of those agri-environmental schemes and rural development measures aimed at enhancing the natural value of farmland and, more generally, aimed at releasing the pressure on the environment due to agriculture. First, based on fine scale data, indicators derived from the High Nature Value farmland concept are tested at different scales, resolutions and situations: LAU2 for The Netherlands and LAU1 for France. The effect of rural development measures on the evolution of these indicators is then explored. Significant cause-effect relationships are found in the French cases, while only relationships of correlations are observed from the Dutch case study, obviously caused by a lack of data. Using fine scale data on rural development measures related to both 2000–2006 and 2007–2013 programming periods of the Common Agricultural Policy, a spatial econometrics methodology is applied to France, at national level on the one hand, and at a selected NUTS2 level on the other. The results indicate that agri-environmental schemes and specific rural development measures affect the changes in the indicators, and that the spatial scale of the analyses matters. In particular, results indicate that trends observed at the national scale do not necessarily apply at the regional scale (e.g. impacts of conversion to organic farming, the grassland premium, payments for water and biodiversity protection) underlining the importance of multi-scale assessments. Interestingly, delayed effects of the measures implemented in the 2000–2006 programming period, such as machinery investment aids and less-favoured area payments, are detectable. As regards the 2007–2013 rural development measures, the most significant positive effects on the farm nature value indicator are found, at the national level, for locally targeted agri-environmental schemes focused on biodiversity and water issues and, at the NUTS2 level, for supporting organic farming schemes. Given that the farm nature value indicator is built from three different indices (addressing crop diversity, grassland share, and wooded and afforested farmland) the effect of rural development measures on each of these individual indices is also explored. This enables the main structure and the magnitude of policy impacts to be captured and helps with the understanding of why certain objectives were not met. Key findings are relevant in the context of policy monitoring and evaluation, while the methodology proposed, that incorporates spatial effects, is an important contribution to the implementation of the Common Monitoring and Evaluation Framework by Member States to account for national, regional or local characteristics.
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