Pulmonary osteoclast-like cells in silica induced pulmonary fibrosis.

The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored mechanisms of silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure to silica and in a longitudinal mouse model of silicosis using multiple modalities including whole-lung single-cell RNA sequencing and histological, biochemical, and physiologic assessments. In addition to pulmonary inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation of alveolar macrophages and recruited monocytes, driven by induction of the osteoclastogenic cytokine, receptor activator of nuclear factor κΒ ligand (RANKL) in pulmonary lymphocytes, and alveolar type II cells. Anti-RANKL monoclonal antibody treatment suppressed silica-induced osteoclast-like differentiation in the lung and attenuated pulmonary fibrosis. We conclude that silica induces differentiation of pulmonary osteoclast-like cells leading to progressive lung injury, likely due to sustained elaboration of bone-resorbing proteases and hydrochloric acid. Interrupting osteoclast-like differentiation may therefore constitute a promising avenue for moderating lung damage in silicosis.

Structure-property relationships in renewable composites of poly(lactic acid) reinforced by low amounts of micro- and nano-kraft-lignin.

We investigate the direct and indirect effects of micro- and nano-kraft lignin, kL and NkL, respectively, at a quite low amount of 0.5 wt%, in poly(lactic acid) (PLA)-based composites. These renewable composites were prepared via two routes, either simple melt compounding or in situ reactive extrusion. The materials are selected and prepared using targeted methods in order to vary two variables, i.e., the size of kL and the synthetic method, while maintaining constant polymer chain lengths, L-/D-lactide isomer ratio and filler amounts. The direct/indirect effects were respectively investigated in the amorphous/semicrystalline state, as crystallinity plays in general a dominant role in polymers. The investigation involves structural, thermal and molecular mobility aspects. Non-extensive polymer-lignin interactions were recorded here, whereas the presence of the fillers led to both enhancements and suppressions of properties, e.g., glass transition, crystallization, melting temperatures, etc. The local and segmental molecular dynamics map of the said systems was constructed and is shown here for the first time, demonstrating both expected and unexpected trends. An interesting discrepancy between the trends in the calorimetric measurement against the dielectric Tg is revealed, providing indications for 'dynamical heterogeneities' in the composites as compared to neat PLA. The reactive extrusion as compared to compounding-based systems was found to exhibit stronger effects on crystallizability and mobility, most, probably due to the severe enhancement of the chains' diffusion. In general, the effects are more pronounced when employing nano-lignin compared to micro-lignin, which is the expected beneficial behaviour of nanocomposites vs. conventional composites. Interestingly, the variety of these effects can be easily manipulated by the proper selection of the preparation method and/or the thermal treatment under relatively mild conditions. The latter capability is actually desirable for processing and targeted applications and is proved here, once again, as an advantage of biobased polyesters such as PLA.

Trend analysis of COVID-19 mis/disinformation narratives-A 3-year study.

To tackle the COVID-19 infodemic, we analysed 58,625 articles from 460 unverified sources, that is, sources that were indicated by fact checkers and other mis/disinformation experts as frequently spreading mis/disinformation, covering the period from 1 January 2020 to 31 December 2022. Our aim was to identify the main narratives of COVID-19 mis/disinformation, develop a codebook, automate the process of narrative classification by training an automatic classifier, and analyse the spread of narratives over time and across countries. Articles were retrieved with a customised version of the Europe Media Monitor (EMM) processing chain providing a stream of text items. Machine translation was employed to automatically translate non-English text to English and clustering was carried out to group similar articles. A multi-level codebook of COVID-19 mis/disinformation narratives was developed following an inductive approach; a transformer-based model was developed to classify all text items according to the codebook. Using the transformer-based model, we identified 12 supernarratives that evolved over the three years studied. The analysis shows that there are often real events behind mis/disinformation trends, which unverified sources misrepresent or take out of context. We established a process that allows for near real-time monitoring of COVID-19 mis/disinformation. This experience will be useful to analyse mis/disinformation about other topics, such as climate change, migration, and geopolitical developments.

Preparation of Cosmetic Emulsions Containing Hippophae Oil Isolated by Various Methods: Study of Their Antioxidant, Sun-Blocking and Physicochemical Properties.

An industry listed as one of the largest globally is the cosmetic industry. In recent years, this industry has shown growing interest in the application of natural ingredients providing advanced properties to cosmetic creams such as moisturizing, antioxidant, sun-protecting and antimicrobial effects. In this context, the present study concerns the production of cosmetic emulsions containing hippophae oil obtained via the methods of extraction, hydro-distillation and maceration using sunflower oil as the carrier oil. Firstly, an IR-ATR analysis was performed showing that the oils prepared were close to those commercially obtained. Then, the stability of the emulsions was tested over a time period of four months through measuring their pH and viscosity values with positive outcomes, and their antioxidant ability was also measured using the DPPH method. The latter one showed that hippophae oil greatly improves the antioxidant capacity. Moreover, based on the fact that sea buckthorn contains carotenoids, the SPF value of the emulsions was determined. The results showed that the addition of hippophae oil to the emulsions gave higher absorption in UV-Vis, thus higher SPF values. Py-GC/MS analysis was used to identify decomposition compounds in the produced oils. Among those, valuable compounds such as Ω-6, Ω-7 and Ω-9 fatty acids and many aldehydes were found by the decomposition of the oils.

Leveraging research infrastructure co-location to evaluate constraints on terrestrial carbon cycling in northern European forests.

Integrated long-term, in-situ observations are needed to document ongoing environmental change, to "ground-truth" remote sensing and model outputs and to predict future Earth system behaviour. The scientific and societal value of in-situ observations increases with site representativeness, temporal duration, number of parameters measured and comparability within and across sites. Research Infrastructures (RIs) can support harmonised, cross-site data collection, curation and publication. Integrating RI networks through site co-location and standardised observation methods can help answers three questions about the terrestrial carbon sink: (i) What are present and future carbon sequestration rates in northern European forests? (ii) How are these rates controlled? (iii) Why do the observed patterns exist? Here, we present a conceptual model for RI co-location and highlight potential insights into the terrestrial carbon sink achievable when long-term in-situ Earth observation sites participate in multiple RI networks (e.g., ICOS and eLTER). Finally, we offer recommendations to promote RI co-location.

Poly(Lactic Acid) Composites with Lignin and Nanolignin Synthesized by In Situ Reactive Processing.

Poly(lactic acid) (PLA) composites with 0.5 wt% lignin or nanolignin were prepared with two different techniques: (a) conventional melt-mixing and (b) in situ Ring Opening Polymerization (ROP) by reactive processing. The ROP process was monitored by measuring the torque. The composites were synthesized rapidly using reactive processing that took under 20 min. When the catalyst amount was doubled, the reaction time was reduced to under 15 min. The dispersion, thermal transitions, mechanical properties, antioxidant activity, and optical properties of the resulting PLA-based composites were evaluated with SEM, DSC, nanoindentation, DPPH assay, and DRS spectroscopy. All reactive processing-prepared composites were characterized by means of SEM, GPC, and NMR to assess their morphology, molecular weight, and free lactide content. The benefits of the size reduction of lignin and the use of in situ ROP by reactive processing were demonstrated, as the reactive processing-produced nanolignin-containing composites had superior crystallization, mechanical, and antioxidant properties. These improvements were attributed to the participation of nanolignin in the ROP of lactide as a macroinitiator, resulting in PLA-grafted nanolignin particles that improved its dispersion.

Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a pulmonary alveolar microlithiasis lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes and other proteins suggested a role for osteoclast-like cells in the host response to microliths. While investigating the mechanisms of microlith clearance, we found that Npt2b modulates pulmonary phosphate homeostasis through effects on alternative phosphate transporter activity and alveolar osteoprotegerin, and that microliths induce osteoclast formation and activation in a receptor activator of nuclear factor-κB ligand and dietary phosphate dependent manner. This work reveals that Npt2b and pulmonary osteoclast-like cells play key roles in pulmonary homeostasis and suggest potential new therapeutic targets for the treatment of lung disease.

Pulmonary osteoclast-like cells in silica induced pulmonary fibrosis.

The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored the mechanisms of silica-induced pulmonary fibrosis in a mouse model using multiple modalities including whole-lung single-nucleus RNA sequencing. These analyses revealed that in addition to pulmonary inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation of alveolar macrophages and recruited monocytes, driven by induction of the osteoclastogenic cytokine, receptor activator of nuclear factor-κB ligand (RANKL) in pulmonary lymphocytes and alveolar type II cells. Furthermore, anti-RANKL monoclonal antibody treatment suppressed silica-induced osteoclast-like differentiation in the lung and attenuated silica-induced pulmonary fibrosis. We conclude that silica induces osteoclast-like differentiation of distinct recruited and tissue resident monocyte populations, leading to progressive lung injury, likely due to sustained elaboration of bone resorbing proteases and hydrochloric acid. Interrupting osteoclast-like differentiation may therefore constitute a promising avenue for moderating lung damage in silicosis.

Effect of Micro- and Nano-Lignin on the Thermal, Mechanical, and Antioxidant Properties of Biobased PLA-Lignin Composite Films.

Bio-based poly(lactic acid) (PLA) composite films were produced using unmodified soda micro- or nano-lignin as a green filler at four different contents, between 0.5 wt% and 5 wt%. The PLA-lignin composite polymers were synthesized by solvent casting to prepare a masterbatch, followed by melt mixing. The composites were then converted into films, to evaluate the effect of lignin content and size on their physicochemical and mechanical properties. Differential scanning calorimetry (DSC), supported by polarized light microscopy (PLM), infrared spectroscopy (FTIR-ATR), X-ray diffraction (XRD), and transmission electron microscopy (TEM) were employed to investigate the PLA crystallization and the interactions with Lignin (L) and Nanolignin (NL). The presence of both fillers (L and NL) had a negligible effect on the glass transition temperature (chain diffusion). However, it resulted in suppression of the corresponding change in heat capacity. This was indicative of a partial immobilization of the PLA chains on the lignin entities, due to interfacial interactions, which was slightly stronger in the case of NL. Lignin was also found to facilitate crystallization, in terms of nucleation; whereas, this was not clear in the crystalline fraction. The addition of L and NL led to systematically larger crystallites compared with neat PLA, which, combined with the higher melting temperature, provided indications of a denser crystal structure in the composites. The mechanical, optical, antioxidant, and surface properties of the composite films were also investigated. The tensile strength and Young's modulus were improved by the addition of L and especially NL. The UV-blocking and antioxidant properties of the composite films were also enhanced, especially at higher filler contents. Importantly, the PLA-NL composite films constantly outperformed their PLA-L counterparts, due to the finer dispersion of NL in the PLA matrix, as verified by the TEM micrographs. These results suggest that bio-based and biodegradable PLA films filled with L, and particularly NL, can be employed as competitive and green alternatives in the food packaging industry.

Formulation, Characterization and Evaluation of Innovative O/W Emulsions Containing Curcumin Derivatives with Enhanced Antioxidant Properties.

In the present study, a series of semisolid Oil in Water (O/W) emulsions containing different Curcumin (Cur) derivatives (Cur powder, Cur extract and Cur complexed with ß-cyclodextrin) in varying concentrations, were prepared. Initially, Dynamic Light Scattering (DLS), microscopy, pH and viscosity measurements were performed to evaluate their stability over time. Moreover, the effect of the active cosmetic substances on the Sun Protection Factor (SPF), antimicrobial and antioxidant properties of the prepared emulsions was investigated. It was observed that emulsions containing Cur extract and Cur ß-cyclodextrin complex presented great viscosity and pH stability for up to 90 days of storage contrary to the emulsions containing Cur powder which showed unstable behavior due to the formation of agglomerates. All samples presented SPF values between 2.6 and 3.2. The emulsions with Cur in all forms exhibited high antioxidant activity, whereas the emulsion containing Cur ß-cyclodextrin complex presented the highest value. Despite their improved stability and antioxidant activity, the emulsions containing Cur extract and Cur-ß-cyclodextrin exhibited a low percentage of antimicrobial activity against E. coli and Staphylococcus bacteria. Instead, the emulsions containing Cur powder presented a reduction rate over 90 % against E. coli and Staphylococcus colonies.

Neonatal haemostatic parameters in correlation to gestational age and birth weight.

INTRODUCTION: The aim of our study was to establish reference ranges for neonatal coagulation and fibrinolysis parameters and to investigate their relationship with gestational age (GA) and birth weight (BW). METHODS: A single-centre prospective study was conducted in all healthy neonates born in our hospital during the study period, excluding those with maternal or neonatal disorders and diseases that affect haemostasis. The following parameters were measured: fibrinogen, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT) as well as factors II, V, VII, VIII, IX, X, XI and XII, von Willebrand (vWF), protein C, free protein S, antithrombin (AT), activated protein C resistance (APCr), tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1). RESULTS: Study population consisted of 327 neonates. Fibrinogen, AT III, proteins C and S, PAI-1, vWF and factors II, V, VIII, IX, XI and XII were positively correlated, while PT, aPPT, INR, APCr and tPA were negatively correlated with GA and BW. Proteins C and S, factors II, VIII, IX, XI and vWF, as well AT III and PAI-1 had a significant positive linear correlation with GA, while aPTT had a significant negative one. Fibrinogen, and factors V, VII and XII had a significant positive linear correlation with BW, while factor VIII, tPA, as well PT and INR had a significant negative one. CONCLUSION: Fibrinogen, AT III, proteins C and S, PAI-1, vWF and factors II, V, VIII, IX, XI and XII increase with GA and BW.

Parvovirus B19 Intrauterine Infection and Eventration of the Diaphragm.

Parvovirus B19 infection in pregnancy may have a poor outcome for the fetus. Ocular anomalies, brain damage with hydrocephalus and central nervous system (CNS) scarring, cleft lip and hypospadias, as well myocarditis and congenital heart disease have been reported. We present a case of a preterm female neonate born with ascites, hydrothorax and congenital diaphragmatic eventration (CDE), with a prenatal diagnosis of congenital diaphragmatic hernia (CDH). The neonate was born prematurely at 32 weeks gestation with caesarean section due to a previous caesarean delivery. She was immediately intubated in the delivery room, transferred in the Neonatal Intensive Care Unit (NICU) and supported with high frequency oscillatory ventilation (HFOV). The diagnosis of CDH was sonographically estimated from the 20th week of gestation and surgical correction was decided. During surgery CDE was diagnosed instead of CDH and despite postoperatively care the neonate developed disseminated intravascular coagulation and finally died in the 40th hour of life. Along with the identification of parvovirus B19 in the pleural fluid by PCR, the biopsy of the diaphragm revealed connective tissue, full of vasculature and absence muscle tissue. Although only cytomegalovirus, rubella, and toxoplasmosis were considered to be associated with CDE, parvovirus B19 might also be related to this congenital diaphragmatic malformation. In CDE, the function of the lungs can be compromised as a consequence of the compression applied by the abdominal organs. The neonatologists should include this condition in their differential diagnosis for a more direct and effective management.

River and lake nutrient targets that support ecological status: European scale gap analysis and strategies for the implementation of the Water Framework Directive.

Eutrophication caused by an excessive presence of nutrients is affecting large portions of European waters with more than 60% of the surface water bodies failing to achieve the primary ambition of water management in Europe, that of good ecological status (GES) with diffuse emission from agriculture being the second most important pressure affecting surface waters. We developed EU wide and regional nutrient targets that define the boundary concentrations between good and moderate status for river and lake total P (TP) and total N (TN) and assessed the gap between actual nutrient concentrations and these targets and considered strategies of nutrient reductions necessary to achieve GES and deliver ecosystem services. The nutrient targets established for rivers ranged from 0.5-3.5 mg/L TN and 11-105 µg/L TP and for lakes 0.5-1.8 mg/L TN and 10-60 µg/L TP. Based on the EU wide targets, 59% of the TN and 57% of the TP river monitoring sites and 64% of the TN and 61% of the TP lake monitoring sites exceed these value and are thus at less than GES. The PCA and step-wise regression for EU basins clearly showed that the basin nutrient export is predominantly related to agricultural inputs. In addition, the step-wise regression models for TN and TP provided the ability to extrapolate the results and quantify the input reductions necessary for reaching the nutrient targets at the EU level. The results suggest that a dual water management strategy would be beneficial and should focus a) on those less polluted rivers and lakes that can easily attain the GES goal and b) on the more highly polluted systems that will improve the delivery of ecosystem services.

Viral Evasion of Innate Immune Defense: The Case of Resistance of Pandemic H1N1 Influenza A Virus to Human Mannose-Binding Proteins.

Mannose-binding lectins effectively inhibit most seasonal strains of influenza A virus and contribute to the innate host defense vs. these viruses. In contrast, pandemic IAV strains are largely resistant to these lectins, likely contributing to increased spread and worse outcomes. In this paper, we evaluated the inhibition of IAV by mannose-binding lectins of human, bacterial, and fungal origin to understand and possibly increase activity vs. the pandemic IAV. A modified version of the human surfactant protein D (SP-D) neck and carbohydrate recognition domain (NCRD) with combinatorial substitutions at the 325 and 343 positions, previously shown to inhibit pandemic H3N2 IAV in vitro and in vivo, and to inhibit pandemic H1N1 in vitro, failed to protect mice from pandemic H1N1 in vivo in the current study. We attempted a variety of maneuvers to improve the activity of the mutant NCRDs vs. the 2009 pandemic H1N1, including the formation of full-length SP-D molecules containing the mutant NCRD, cross-linking of NCRDs through the use of antibodies, combining SP-D or NCRDs with alpha-2-macroglobulin, and introducing an additional mutation to the double mutant NCRD. None of these substantially increased the antiviral activity for the pandemic H1N1. We also tested the activity of bacterial and algal mannose-binding lectins, cyanovirin, and griffithsin, against IAV. These had strong activity against seasonal IAV, which was largely retained against pandemic H1N1. We propose mechanisms to account for differences in activity of SP-D constructs against pandemic H3N2 and H1N1, and for differences in activity of cyanovirin vs. SP-D constructs.

A neonate with late-onset hypocalcemia due to unrecognized maternal hyperparathyroidism and a systematic overview of similar cases.

Objective: Neonatal seizures are alarming manifestations of an underlying significant disorder demanding immediate attention and intervention. Hypocalcemia, although rare, must be considered in the differential diagnosis of neonatal seizures. Method: We present an unusual case of a 10-day-old infant with unexplained symptomatic hypocalcemia, experiencing multiple episodes of focal tonic-clonic seizures, born by an entirely asymptomatic mother. Moreover, we conducted a systematic search in PubMed and Scopus databases to present a clinical overview of all similar cases. Result: Maternal laboratory investigation revealed markedly increased calcium levels with concomitant high parathyroid hormone levels due to a parathyroid adenoma, undiagnosed during antenatal checkup. Conclusion: This is one of the few cases in the literature where neonatal symptomatology led to the diagnosis of undiagnosed maternal hyperparathyroidism. Early detection and appropriate management of neonatal hypocalcemia could eliminate serious maternal and fetal morbidity.

Innovative Skin Product Emulsions with Enhanced Antioxidant, Antimicrobial and UV Protection Properties Containing Nanoparticles of Pure and Modified Chitosan with Encapsulated Fresh Pomegranate Juice.

In the present study, a chitosan (CS) derivative with the 2-(Methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SDAEM) zwitterionic monomer was prepared through chemical modification. The successful synthesis of CS-SDAEM was confirmed by Fourier-transform Infrared (FTIR) and Nuclear Magnetic Resonance (1H-NMR) spectroscopies. Its crystallinity was studied by X-ray Diffraction (XRD), while in vitro cytotoxicity and cell viability assays established its biocompatibility. Filtered fresh pomegranate juice (PJ) was loaded in nanoparticles of neat CS and its derivative via ionic gelation method. Dynamic Light Scattering (DLS) revealed nanoparticles sizes varying between 426 nm and 4.5 µm, indicating a size-dependence on the polymer concentration used during encapsulation. High-performance liquid chromatography coupled with photodiode array and electrospray ionization mass spectrometry detection (LC-PDA-ESI/MS) revealed that PJ active compounds were successfully and in sufficient amounts encapsulated in the nanoparticles interior, whereas XRD indicated a crystalline structure alteration after nanoencapsulation. The resulted PJ-loaded nanoparticles were further utilized for the preparation of innovative O/W cosmetic emulsions. All produced emulsions exhibited good pH and viscosity stability for up to 90 days, while the sun protection factor (SPF) was enhanced due to the presence of the PJ. Enhanced antioxidant and antimicrobial properties due to the phenolic compounds of PJ were also observed.

Estimation of the uncertainty of hydrologic predictions in a karstic Mediterranean watershed.

The Koiliaris River basin is a semi-arid Mediterranean karstic watershed where water needs during the summer are exclusively covered by the karstic springs flow. Uncertainty assessment of the hydrologic projections for karstic watersheds may reveal possible water deficits that cannot otherwise be taken into account. The Soil Water Assessment Tool (SWAT) along with a karstic model (Karst-SWAT) is used to assess the composite spring and surface flow. The parameter uncertainty of both the surface and karstic flow models is estimated by combining the SUFI2 interface and the @RISK by PALISADE software. Eleven combinations of five Regional Climate Models (RCMs) and three Representative Concentration Pathways (RCPs) provide input to the hydrologic models. Representative rainfall time series for certain scenarios are stochastically modeled with the LARS weather generator. Monte Carlo simulations are used to investigate the effect of input internal variability on the flow output. The uncertainty of karstic flow due to the parameter uncertainty of the SWAT and Karst-SWAT models is 10.0% (Coefficient of Variation), which is comparable to the estimated uncertainty due to climate change scenarios (10.1%) until 2059. The combined uncertainty for the total flow at the basin exit due to both models' parameter uncertainty is 6.6%, comparable to the uncertainty due to the internal variability (5.6%). The total uncertainty of karstic flow, combining model parameter uncertainty and the internal variability of the climate scenarios is 11.0%. The total uncertainty estimate is used in conjunction with the lowest karstic flow projection to assess the most adverse scenario for the future mean annual karstic flow. This is the first study which estimates the combined uncertainty of surface and karstic flow prediction due to model parameter uncertainty and internal variability. Our study provides a rigorous methodology for uncertainty estimation and analysis which is transferable to other karstic regions of the world.

Evaluation of cerebral oxygenation and perfusion in small for gestational age neonates and neurodevelopmental outcome at 24-36 months of age.

Objective To examine cerebral oxygenation and perfusion in small for gestational age (SGA) compared with appropriate for gestational age (AGA) neonates during the first postnatal week, and to investigate any association with neurodevelopmental outcomes at 24-36 months of age. Methods A prospective matched case-control study was conducted evaluating cerebral oxygenation and perfusion, using near-infrared spectroscopy (NIRS), between SGA and AGA neonates, during the first postnatal week. A neurodevelopmental assessment with Bayley-III was performed at 24-36 months of age. Results Forty-eight SGA and 48 AGA neonates of similar gestation (32.8 ± 2.1 vs. 32.5 ± 1.9) were enrolled. On the first postnatal day, the cerebral oxygenation was equal between SGA and AGA neonates (71 ± 7% vs. 72 ± 8%); however, in the subgroup analysis, males had higher oxygenation compared to female SGA neonates (73 ± 7% vs. 69 ± 7%, P = 0.04). Cerebral perfusion was significantly higher in SGA neonates on the first postnatal day (1.4 ± 0.6 vs. 1.1 ± 0.5, P = 0.04), but this difference was diminished on subsequent measurements. There were no significant differences between the SGA and AGA infants regarding the composite cognitive, communication and motor index scores. The length of mechanical ventilation and late-onset sepsis were significant risk factors affecting the cognitive and communication composite index scores, respectively. Conclusion Cerebral oxygenation was equal between SGA and AGA neonates, while cerebral perfusion was transiently increased in SGA neonates during the first postnatal day. There was no significant association of cerebral oxygenation and perfusion with neurodevelopmental outcomes.

Research questions to facilitate the future development of European long-term ecosystem research infrastructures: A horizon scanning exercise.

Distributed environmental research infrastructures are important to support assessments of the effects of global change on landscapes, ecosystems and society. These infrastructures need to provide continuity to address long-term change, yet be flexible enough to respond to rapid societal and technological developments that modify research priorities. We used a horizon scanning exercise to identify and prioritize emerging research questions for the future development of ecosystem and socio-ecological research infrastructures in Europe. Twenty research questions covered topics related to (i) ecosystem structures and processes, (ii) the impacts of anthropogenic drivers on ecosystems, (iii) ecosystem services and socio-ecological systems and (iv), methods and research infrastructures. Several key priorities for the development of research infrastructures emerged. Addressing complex environmental issues requires the adoption of a whole-system approach, achieved through integration of biotic, abiotic and socio-economic measurements. Interoperability among different research infrastructures needs to be improved by developing standard measurements, harmonizing methods, and establishing capacities and tools for data integration, processing, storage and analysis. Future research infrastructures should support a range of methodological approaches including observation, experiments and modelling. They should also have flexibility to respond to new requirements, for example by adjusting the spatio-temporal design of measurements. When new methods are introduced, compatibility with important long-term data series must be ensured. Finally, indicators, tools, and transdisciplinary approaches to identify, quantify and value ecosystem services across spatial scales and domains need to be advanced.