Search

Quantitative reconstructions of past land cover are necessary to determine the processes involved in climate–human–land-cover interactions. We present the first temporally continuous and most spatially extensive pollen-based land-cover reconstruction for Europe over the Holocene (last 11 700 cal yr BP). We describe how vegetation cover has been quantified from pollen records at a 1∘ × 1∘ spatial scale using the “Regional Estimates of VEgetation Abundance from Large Sites” (REVEALS) model. REVEALS calculates estimates of past regional vegetation cover in proportions or percentages. REVEALS has been applied to 1128 pollen records across Europe and part of the eastern Mediterranean–Black Sea–Caspian corridor (30–75∘ N, 25∘ W–50∘ E) to reconstruct the percentage cover of 31 plant taxa assigned to 12 plant functional types (PFTs) and 3 land-cover types (LCTs). A new synthesis of relative pollen productivities (RPPs) for European plant taxa was performed for this reconstruction. It includes multiple RPP values (≥2 values) for 39 taxa and single values for 15 taxa (total of 54 taxa). To illustrate this, we present distribution maps for five taxa (Calluna vulgaris, Cerealia type (t)., Picea abies, deciduous Quercus t. and evergreen Quercus t.) and three land-cover types (open land, OL; evergreen trees, ETs; and summer-green trees, STs) for eight selected time windows. The reliability of the REVEALS reconstructions and issues related to the interpretation of the results in terms of landscape openness and human-induced vegetation change are discussed. This is followed by a review of the current use of this reconstruction and its future potential utility and development. REVEALS data quality are primarily determined by pollen count data (pollen count and sample, pollen identification, and chronology) and site type and number (lake or bog, large or small, one site vs. multiple sites) used for REVEALS analysis (for each grid cell). A large number of sites with high-quality pollen count data will produce more reliable land-cover estimates with lower standard errors compared to a low number of sites with lower-quality pollen count data. The REVEALS data presented here can be downloaded from https://doi.org/10.1594/PANGAEA.937075 (Fyfe et al., 2022).

The Eurasian (née European) Modern Pollen Database (EMPD) was established in 2013 to provide a public database of high-quality modern pollen surface samples to help support studies of past climate, land cover, and land use using fossil pollen. The EMPD is part of, and complementary to, the European Pollen Database (EPD) which contains data on fossil pollen found in Late Quaternary sedimentary archives throughout the Eurasian region. The EPD is in turn part of the rapidly growing Neotoma database, which is now the primary home for global palaeoecological data. This paper describes version 2 of the EMPD in which the number of samples held in the database has been increased by 60 % from 4826 to 8134. Much of the improvement in data coverage has come from northern Asia, and the database has consequently been renamed the Eurasian Modern Pollen Database to reflect this geographical enlargement. The EMPD can be viewed online using a dedicated map-based viewer at https://empd2.github.io and downloaded in a variety of file formats at https://doi.pangaea.de/10.1594/PANGAEA.909130 (Chevalier et al., 2019).

Pollen and clay mineralogical analyses of a Holocene sequence from Sebkha Boujmel (southern Tunisia) trace the climatic and environmental dynamics in the lower arid bioclimatic zone over the last 8000 years. During the mid- to late Holocene transition, between ca. 8 and 3 ka BP, a succession of five wet–dry oscillations is recorded. An intense arid event occurs between ca. 5.7 and 4.6 ka BP. This episode marks the onset of a long-term aridification trend with a progressive retreat of Mediterranean woody xerophytic vegetation and of grass steppes. It ends with the establishment of pre-desert ecosystems around 3 ka BP. The millennial-scale climate change recorded in the data from Sebkha Boujmel is consistent with records from the south and east Mediterranean, as well as with climatic records from the desert region for the end of the African Humid Period (AHP). Eight centennial climatic events are recorded at Sebkha Boujmel and these are contemporary with those recorded in the Mediterranean and in the Sahara. They indicate a clear coupling between the southern Mediterranean and the Sahara before 3 ka BP. The event at 4.2 ka BP is not evidenced and the link between events recorded in Sebkha Boujmel and the North Atlantic cooling events is clearer from ca. 3 ka BP onwards. These variations indicate the importance of climatic determinism in the structuring of landscapes, with the establishment of the arid climatic conditions of the late Holocene. It is only from ca. 3 ka BP onwards that the dynamic of plant associations is modified by both human activity and climatic variability. The climatic episodes identified during the historic period indicate strong regionalisation related to the differential impact of the North Atlantic Oscillation (NAO) and the Mediterranean Oscillation (MO) on the Mediterranean Basin. The local human impact on regional ecosystems is recorded in the form of episodes of intensification of pastoral and/or agricultural activities. The development of olive production and of several taxa associated with agriculture attest to increasing sedentism among human populations during classical antiquity. The significant increase in Artemisia (wormwood) between ca. 1.1 and 0.8 ka BP (850–1150 AD) is linked to intensive pastoral activity, associated with heightened interannual and/or seasonal climatic instability. A complete reshaping of the landscape is recorded during the 20th century. The remarkable expansion of the olive tree, and the deterioration of regional ecosystems with the spread of desert species, is linked to recent local socio-economic changes in Tunisia.

Holocene climate fluctuations and human activity since the Neolithic have shaped present-day Mediterranean environments. Separating anthropogenic effects from climatic impacts to better understand Mediterranean paleoenvironmental changes over the last millennia remains a challenging issue. High-resolution pollen analyses were undertaken on two cores from the Palavasian lagoon system (Hérault, southern France). These records allow reconstruction of vegetation dynamics over the last 4500 years. Results are compared with climatic, historical and archeological archives. A long-term aridification trend is highlighted during the late Holocene, and three superimposed arid events are recorded at 4600–4300, 2800–2400 and 1300–1100 cal BP. These periods of high-frequency climate variability coincide in time with the rapid climatic events observed in the Atlantic Ocean (Bond et al., 2001). From the Bronze Age (4000 cal BP) to the end of the Iron Age (around 2000 cal BP), the spread of sclerophyllous taxa and loss of forest cover result from anthropogenic impact. Classical Antiquity is characterized by a major reforestation event related to the concentration of rural activity and populations in coastal plains leading to forest recovery in the mountains. A major regional deforestation occurred at the beginning of the High Middle Ages. Around 1000 cal BP, forest cover is minimal while the cover of olive, chestnut and walnut expands in relation to increasing human influence. The present-day vegetation dominated by Mediterranean shrubland and pines has been in existence since the beginning of the 20th century.

The palaeobotanical record of early Palaeolithic sites from Western Europe indicates that hominins settled in different kinds of environments. During the "mid-Pleistocene transition (MPT)", from about 1 to 0.6 Ma, the transition from 41- to 100-ka dominant climatic oscillations, occurring within a long-term cooling trend, was associated with an aridity crisis which strongly modified the ecosystems. Starting from the MPT the more favourable climate of central and southern Italy provided propitious environmental conditions for long-term human occupations even during the glacial times. In fact, the human strategy of territory occupation was certainly driven by the availabilities of resources. Prehistoric sites such as Notarchirico (ca. 680–600 ka), La Pineta (ca. 600–620 ka), Guado San Nicola (ca. 380–350 ka) or Ceprano (ca. 345–355 ka) testify to a preferential occupation of the central and southern Apennines valleys during interglacial phases, while later interglacial occupations were oriented towards the coastal plains, as attested by the numerous settlements of the Roma Basin (ca. 300 ka). Faunal remains indicate that human subsistence behaviours benefited from a diversity of exploitable ecosystems, from semi-open to closed environments. In central and southern Italy, several palynological records have already illustrated the regional- and local-scale vegetation dynamic trends. During the Middle Pleistocene climate cycles, mixed mesophytic forests developed during the interglacial periods and withdrew in response to increasing aridity during the glacial episodes. New pollen data from the Boiano Basin (Molise, Italy) attest to the evolution of vegetation and climate between MIS 13 and 9 (ca. 500 to 300 ka). In this basin the persistence of high edaphic humidity, even during the glacial phases, could have favoured the establishment of a refuge area for the arboreal flora and provided subsistence resources for the animal and hominin communities during the Middle Pleistocene. This could have constrained human groups to migrate into such a propitious area. Regarding the local climate evolution during the glacial episodes, the supposed displacement from these sites could be linked to the environmental dynamics solely due to the aridity increase, rather than directly to the global climate changes.

Aim: The present study investigated renal elimination after intravenous administration of four different formulations of lipid nanocapsules (LNCs) containing dyes adapted to Förster resonance energy transfer (FRET-LNCs). Materials & methods: FRET-LNCs of 85 or 50 nm with or without a pegylated surface were injected and collected in the blood or urine of rats at different time points. Quantitative analysis was performed to measure intact FRET-LNCs. Results & conclusion: No intact LNCs were found in urine (0 particles/ml) for all formulations. The 50-nm pegylated LNCs were eliminated faster from the blood, whereas 85-nm pegylated LNCS were eliminated slower than nonpegylated LNCs. Elimination of FRET-LNCs was mainly due to liver tissue interaction and not renal elimination.

The parameters currently used for characterization of nanoparticles, such as size and zeta potential, were not able to reflect the performance of a nanocarrier in the biological environment. Therefore, more thorough in vitro characterization is required to predict their behavior in vivo, where nanoparticles acquire a new biological identity due to interactions with biomolecules. In this present study, we performed in vitro characterization in biological fluids for lipid nanocapsules (LNCs) with varying means sizes (50 nm and 100 nm), different electrical surface charges and different Poly Ethylene Glycol (PEG) compositions. Then, different methods were applied to show the impact of the protein corona formation on LNCs. Even if all formulations attached to plasmatic proteins, a higher thickness of corona and highest protein binding was observed for certain LNC50 formulations. A better knowledge of the phenomenon of protein adsorption over NPs in the plasmatic media is a cornerstone of clinical translation. In fact, after short blood circulation time, it is not the initially designed nanoparticle but the complex nanoparticle bearing its protein corona which circulates to reach its target., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The present study investigated the pharmacokinetics of intact lipid nanocapsules (LNCs) after intravenous administration in rats. Six different Förster resonance energy transfer LNCs (FRET-LNCs) have been studied with 2 sizes (50 and 85 nm) and 3 coating types (none, DSPE-mPEG 2000 or stearylamine). A FRET-LNCs blood extraction method was developed to retain an accurate FRET signal. Intact FRET-LNCs were specifically quantified through combination of FRET signal and Nano Tracker Analysis. Pharmacokinetic data were first described by non-compartmental analysis, then used to develop a population pharmacokinetic model. The pharmacokinetic elimination of FRET-LNCs was non-linear and dependent on size and surface modification, while the distribution was dependent on size. The LNCs 85 nm volume of distribution was lower than LNCs 50 nm. As expected, LNCs 85 nm with PEG coating displayed a lower clearance than other formulations. Surprisingly, this study highlighted a faster elimination of LNCs 50 nm with PEG compared to other formulations which could be explained by instability in blood. This first pharmacokinetic model of intact LNCs allowed a thorough understanding of the influence of size and coating on pharmacokinetic properties and paves the way for future mechanistic modeling approaches to predict the fate of LNCs in vivo., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Idarubicin (IDA) is an antineoplasic drug commonly used to treat hematologic diseases. Because of its relative lipophilic properties, this anthracycline is also used in transarterial chemoembolization (TACE) as part of hepatocellular carcinoma (HCC) treatment. But TACE requires injected volume to be reduced to restrict systemic diffusion and side effects. The aim of this study was to determine the stability of a highly concentrated aqueous solution of IDA, stored in polypropylene syringes between 2 °C and 8 °C. Analyses were performed with an HPLC system combined with UV detector and mass spectrometer. Forced degradation was used to investigate potential degradation products. This study demonstrated 7 days of stability after storage in previously mentioned conditions. This conservation is long enough to anticipate drug preparation and facilitates pharmacy organization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nanomedicines have been developed for more than four decades to optimize the pharmacokinetics (PK) of drugs, especially absorption, distribution, and stability in vivo. Unfortunately, only a few drug products have reached the market. One reason among others is the lack of proper PK modeling and evaluation, which impedes the optimization of these promising drug delivery systems. In this review, we discuss the specificity of nanomedicines and propose key parameters to take into account for future accurate PK evaluation of nanomedicine. We believe that this could help these innovative drug products to reach to market and change the fate of many diseases., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: Ciclosporin A (CsA) is used in the prophylaxis and treatment of acute and chronic graft vs. host disease after haematopoietic stem cell (HSCT) transplantation. Our objective was to build and compare three independent Bayesian estimators of CsA area under the curve (AUC) using a limited sampling strategy (LSS), to assist in dose adjustment., Methods: The Bayesian estimators were developed using in parallel: two independent parametric modelling approaches (nonmem® and iterative two stage (ITS) Bayesian modelling) and the non-parametric adaptive grid method (Pmetrics®). Seventy-two full pharmacokinetic profiles (at pre-dose and 0.33, 0.66, 1, 2, 3, 4, 6, 8 and 12h after dosing) collected from 40 HSCT patients given CsA were used to build the pharmacokinetic models, while 15 other profiles (n = 7) were kept for validation. For each Bayesian estimator, AUCs estimated using the full profiles were compared with AUCs estimated using three samples., Results: The pharmacokinetic profiles were well fitted using a two compartment model with first order elimination, combined with a gamma function for the absorption phase with ITS and Pmetrics or an Erlang distribution with nonmem. The derived Bayesian estimators based on a C0-C1 h-C4 h sampling schedule (best LSS) accurately estimated CsA AUC(0,12 h) in the validation group (n = 15; nonmem: bias (mean ± SD)/RMSE 2.05% ± 13.31%/13.02%; ITS: 4.61% ± 10.56%/11.20%; Pmetrics: 0.30% ± 10.12%/10.47%). The dose chosen confronting the three results led to a pertinent dose proposal., Conclusions: The developed Bayesian estimators were all able to predict ciclosporin AUC(0,12 h) in HSCT patients using only three blood with minimal bias and may be combined to increase the reliability of CsA dose adjustment in routine., (© 2014 The British Pharmacological Society.)

A monoclonal antibody was obtained from BALB/c mice immunized with Penicillium frequentans mycelium. The specificity of the antibody was evaluated by enzyme-linked immunosorbent and indirect immunofluorescence assays against the same mycelium. This IgM antibody cross-reacted with various strains of the Penicillium and Aspergillus genera. By indirect immunofluorescence assays, the antibody was able to stain about 10% of Penicillium and Aspergillus conidia, but major part of conidia did not absorb the fluorescence-labeled antibody before swelling. During germination of P. frequentans conidia, the germ tube wall which constitutes a continuation of an inner wall layer was also stained. During germination of P. griseofulvum, the protrusion of the germ tube wall was not always recognized by the antibody because the germ tube wall was constituted by a continuation of an outer spore wall layer. The study of the staining patterns of the spores and the protrusions suggests that the antibody specifically recognizes an antigen of the inner spore wall layer. The monoclonal antibody reacts with extracellular galactomannans produced by genera Aspergillus and Penicillium but is not directed against beta-(1,5)-linked galactofuranose units.