The Impact of Caesarean Delivery on Paracetamol and Ketorolac Pharmacokinetics: A Paired Analysis

Pharmacokinetics is a first, but essential step to improve population-tailored postoperative analgesia, also after Caesarean delivery. We therefore aimed to quantify the impact of caesarean delivery on the pharmacokinetics of intravenous (iv) paracetamol (2 g, single dose) and iv ketorolac tromethamine (30 mg, single dose) in 2 cohorts eachof 8 women at caesarean delivery and to compare these findings with postpartum to quantify intrapatient changes. We documented a higher median paracetamol clearance at delivery when compared to 10–15 weeks postpartum (11.7 to 6.4 L/h·m2, P < 0.01), even after correction for weight-related changes. Similar conclusions were drawn for ketorolac: median clearance was higher at delivery with a subsequent decrease (2.03 to 1.43 L/h·m2, P < 0.05) in postpartum (17–23 weeks). These differences likely reflect pregnancy- and caesarean-delivery-related changes in drug disposition. Moreover, postpartum paracetamol clearance was significantly lower when compared to estimates published in healthy young volunteers (6.4  versus  9.6 L/h·m2), while this was not the case for ketorolac (1.43  versus  1.48 L/h·m2). This suggests that postpartum is another specific status in young women that merits focused, compound-specific pharmacokinetic evaluation

Comportement De Territorialité De Propithecus Deckenii Dans Les Aires Protégées Complexe Tsimembo Manambolomaty Et Mandrozo

This study aims to understand the behavior territoriality of the lemur Decken's Sifaka Propithecus deckenii in the Protected Areas (PAs) Complexe Tsimembo Manambolomaty and Mandrozo in the central-west of Madagascar between November 2017 and April 2018, and between July and October 2018. The continuous focal animal sampling method was used to monitor eight groups of Sifakas, two groups of the intact habitat and two groups from the disturbed habitat in each PA. Scent marking frequencies per focal groups differs between the two habitats types and is influenced by sex in favor of males. Season does not impacted this activity. The home range (define by MCP and 95% Kernel density estimate) and core area varies between monitored groups and the daily path length can reach 234 ± 98 m to 362 ± 110 m. These parameters are not influenced by season and habitat types. However, the intensity of territory use does not have any variation among the studied groups. The mean average « defensibility index » value for P. deckenii is 1.74 ± 0.70 (n = 8). The studied species has ability to adjust their territorial behavior, despite the degradation of habitat in sustainable use zone

Glucocorticoid-Induced TNF Receptor Family-Related Protein Ligand is Requisite for Optimal Functioning of Regulatory CD4+ T Cells

Glucocorticoid-induced tumor necrosis factor receptor family-related protein (TNFRSF18, CD357) is constitutively expressed on regulatory T cells (Tregs) and is inducible on effector T cells. In this report, we examine the role of glucocorticoid-induced TNF receptor family-related protein ligand (GITR-L), which is expressed by antigen presenting cells, on the development and expansion of Tregs. We found that GITR-L is dispensable for the development of naturally occurring FoxP3+ Treg cells in the thymus. However, the expansion of Treg in GITR-L−/− mice is impaired after injection of the dendritic cells (DCs) inducing factor Flt3 ligand. Furthermore, DCs from the liver of GITR-L−/− mice were less efficient in inducing proliferation of antigen-specific Treg cells in vitro than the same cells from WT littermates. Upon gene transfer of ovalbumin into hepatocytes of GITR-L−/−FoxP3(GFP) reporter mice using adeno-associated virus (AAV8-OVA) the number of antigen-specific Treg in liver and spleen is reduced. The reduced number of Tregs resulted in an increase in the number of ovalbumin specific CD8+ T effector cells. This is highly significant because proliferation of antigen-specific CD8+ cells itself is dependent on the presence of GITR-L, as shown by in vitro experiments and by adoptive transfers into GITR-L−/−Rag−/− and Rag−/− mice that had received AAV8-OVA. Surprisingly, administering αCD3 significantly reduced the numbers of FoxP3+ Treg cells in the liver and spleen of GITR-L−/− but not WT mice. Because soluble Fc-GITR-L partially rescues αCD3 induced in vitro depletion of the CD103+ subset of FoxP3+CD4+ Treg cells, we conclude that expression of GITR-L by antigen presenting cells is requisite for optimal Treg-mediated regulation of immune responses including those in response during gene transfer

Effects of turbidity and introduced tilapia (Oreochromis spp) on macrophytes and invertebrates in a shallow tropical lake

Tropical freshwater wetlands are subject to multiple stressors but there is little information on which stressors cause wetland degradation. Increased turbidity is considered a major cause of degradation, but the effects of introduced fish are often overlooked. Tilapia are frequently introduced in tropical regions, especially species in the genus Oreochromis, and the ecological effects of introducing tilapia are poorly studied. We used enclosure experiments in a shallow lake in Madagascar to assess the effects of tilapia and turbidity on macrophytes and benthic invertebrates, and to test management interventions designed to increase both. Tilapia at high and low stocking densities had negative effects on survival of Charophyte algae and water lilies, but no direct effect on benthic invertebrate abundance or diversity. Invertebrate abundance was highest on submerged Charophytes, so herbivory by tilapia indirectly affected invertebrates. Turbidity affected Charophyte survival, and abundance and diversity of non-Dipteran insects. As a complication, tilapia may increase turbidity by re-suspending the lake sediment. Our results suggest that herbivory by tilapia is a plausible cause of the removal of macrophytes from the lake and an impediment to their re-establishment. Tilapia are widely introduced in tropical areas as a food resource. Our results demonstrate serious consequences to these introductions

Predictive value of quantitative F-18-FDG-PET radiomics analysis in patients with head and neck squamous cell carcinoma

BACKGROUND: Radiomics is aimed at image-based tumor phenotyping, enabling application within clinical-decision-support-systems to improve diagnostic accuracy and allow for personalized treatment. The purpose was to identify predictive 18-fluor-fluoro-2-deoxyglucose (18F-FDG) positron-emission tomography (PET) radiomic features to predict recurrence, distant metastasis, and overall survival in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy. METHODS: Between 2012 and 2018, 103 retrospectively (training cohort) and 71 consecutively included patients (validation cohort) underwent 18F-FDG-PET/CT imaging. The 434 extracted radiomic features were subjected, after redundancy filtering, to a projection resulting in outcome-independent meta-features (factors). Correlations between clinical, first-order 18F-FDG-PET parameters (e.g., SUVmean), and factors were assessed. Factors were combined with 18F-FDG-PET and clinical parameters in a multivariable survival regression and validated. A clinically applicable risk-stratification was constructed for patients' outcome. RESULTS: Based on 124 retained radiomic features from 103 patients, 8 factors were constructed. Recurrence prediction was significantly most accurate by combining HPV-status, SUVmean, SUVpeak, factor 3 (histogram gradient and long-run-low-grey-level-emphasis), factor 4 (volume-difference, coarseness, and grey-level-non-uniformity), and factor 6 (histogram variation coefficient) (CI = 0.645). Distant metastasis prediction was most accurate assessing metabolic-active tumor volume (MATV)(CI = 0.627). Overall survival prediction was most accurate using HPV-status, SUVmean, SUVmax, factor 1 (least-axis-length, non-uniformity, high-dependence-of-high grey-levels), and factor 5 (aspherity, major-axis-length, inversed-compactness and, inversed-flatness) (CI = 0.764). CONCLUSIONS: Combining HPV-status, first-order 18F-FDG-PET parameters, and complementary radiomic factors was most accurate for time-to-event prediction. Predictive phenotype-specific tumor characteristics and interactions might be captured and retained using radiomic factors, which allows for personalized risk stratification and optimizing personalized cancer care. TRIAL REGISTRATION: Trial NL3946 (NTR4111), local ethics commission reference: Prediction 2013.191 and 2016.498. Registered 7 August 2013, https://www.trialregister.nl/trial/3946

Protected area surface extension in Madagascar: Do endemism and threatened species remain useful criteria for site selection?

The ‘hotspot approach’ considers that endemism and threatened species are key factors in protected area designation. Three wetland and forest sites have been proposed to be included into Madagascar’s system of protected areas (SAPM – Système des Aires Protégées de Madagascar). These sites are Manambolomaty (14,701 ha) and Mandrozo (15,145 ha) in the west and Bemanevika (37,041 ha) in the north. Biodiversity inventories of these three sites recorded 243 endemic species comprised of 44 reptiles, 54 amphibians, 104 birds, 23 small mammals, 17 lemurs and one fish. Of these 243 species, 30 are threatened taxa comprising two Critically Endangered (CR), 11 Endangered (EN) and 17 Vulnerable (VU) species. The long term ecological viability of these sites has been shown by population stability of the two Critically Endangered flagship species, the Madagascar fish eagle (Haliaeetus vociferoides) in Manambolomaty and Mandrozo and the recently rediscovered Madagascar pochard (Aythya innotata) in Bemanevika. Other threatened species and high biological diversity also justifies their inclusion into Madagascar’s SAPM.RÉSUMÉL’endémisme et les espèces menacées constituent les éléments clef pour la création des aires protégées. Trois zones humides de Madagascar ainsi que leurs forêts avoisinantes sont proposées pour la protection sous le nouveau système des aires protégées malgaches connu sous le sigle SAPM (Système d’Aires Protégées de Madagascar) : Manambolomaty (14.701 ha) et Mandrozo (15.145 ha) à l’Ouest et Bemanevika (37.041 ha) dans le Nord. Les inventaires biologiques entrepris dans ces trois sites ont montré que 243 espèces y sont endémiques, avec 44 reptiles, 54 amphibiens, 104 oiseaux, 23 petits mammifères, 17 lémuriens et un poisson. Parmi ces 243 espèces, 30 sont menacées d’extinction avec deux qui sont en danger critique d’extinction (CR), 11 en danger (EN) et 17 vulnérables (VU). La survie écologique à long terme de ces sites a été avérée avec la découverte de la stabilité des populations des deux espèces indicatrices en danger critique d’extinction que sont le Pygargue de Madagascar (Haliaeetus vociferoides) à Manambolomaty et Mandrozo et une espèce récemment redécouverte, le Fuligule de Madagascar (Aythya innotata) à Bemanevika. La stabilité de plusieurs autres espèces menacées ainsi que la diversité biologique de ces sites justifient leur inclusion dans le SAPM. Les sept associations locales, deux à Manambolomaty, deux à Bemanevika et trois à Mandrozo, ont supporté le programme de suivi de ces sites ainsi que de ces espèces indicatrices en montrant ainsi leur engagement dans le processus de création des aires protégées. Le Peregrine Fund a travaillé dans ces sites en vue de mettre en synergie ses objectifs de conservation avec le développement socio-économique local

Protected area surface extension in Madagascar: Do endemism and threatened species remain useful criteria for site selection ?

The ‘hotspot approach’ considers that endemism and threatened species are key factors in protected area designation. Three wetland and forest sites have been proposed to be included into Madagascar’s system of protected areas (SAPM – Système des Aires Protégées de Madagascar). These sites are Manambolomaty (14,701 ha) and Mandrozo (15,145 ha) in the west and Bemanevika (37,041 ha) in the north. Biodiversity inventories of these three sites recorded 243 endemic species comprised of 44 reptiles, 54 amphibians, 104 birds, 23 small mammals, 17 lemurs and one fish. Of these 243 species, 30 are threatened taxa comprising two Critically Endangered (CR), 11 Endangered (EN) and 17 Vulnerable (VU) species. The long term ecological viability of these sites has been shown by population stability of the two Critically Endangered flagship species, the Madagascar fish eagle (Haliaeetus vociferoides) in Manambolomaty and Mandrozo and the recently rediscovered Madagascar pochard (Aythya innotata) in Bemanevika. Other threatened species and high biological diversity also justifies their inclusion into Madagascar’s SAPM.RÉSUMÉL’endémisme et les espèces menacées constituent les éléments clef pour la création des aires protégées. Trois zones humides de Madagascar ainsi que leurs forêts avoisinantes sont proposées pour la protection sous le nouveau système des aires protégées malgaches connu sous le sigle SAPM (Système d’Aires Protégées de Madagascar) : Manambolomaty (14.701 ha) et Mandrozo (15.145 ha) à l’Ouest et Bemanevika (37.041 ha) dans le Nord. Les inventaires biologiques entrepris dans ces trois sites ont montré que 243 espèces y sont endémiques, avec 44 reptiles, 54 amphibiens, 104 oiseaux, 23 petits mammifères, 17 lémuriens et un poisson. Parmi ces 243 espèces, 30 sont menacées d’extinction avec deux qui sont en danger critique d’extinction (CR), 11 en danger (EN) et 17 vulnérables (VU). La survie écologique à long terme de ces sites a été avérée avec la découverte de la stabilité des populations des deux espèces indicatrices en danger critique d’extinction que sont le Pygargue de Madagascar (Haliaeetus vociferoides) à Manambolomaty et Mandrozo et une espèce récemment redécouverte, le Fuligule de Madagascar (Aythya innotata) à Bemanevika. La stabilité de plusieurs autres espèces menacées ainsi que la diversité biologique de ces sites justifient leur inclusion dans le SAPM. Les sept associations locales, deux à Manambolomaty, deux à Bemanevika et trois à Mandrozo, ont supporté le programme de suivi de ces sites ainsi que de ces espèces indicatrices en montrant ainsi leur engagement dans le processus de création des aires protégées. Le Peregrine Fund a travaillé dans ces sites en vue de mettre en synergie ses objectifs de conservation avec le développement socio-économique local

Impact of donor lung quality on post-transplant recipient outcome in the Lung Allocation Score era in Eurotransplant - a historical prospective study

The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current LAS era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N=3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤ 45 years, p<0.0001), were less often smokers (35% vs. 46%, p<0.0001), had more often clear chest X-rays (82% vs. 72%, p<0.0001), had better donor oxygenation ratio's (20% vs. 26% with PaO /FiO ≤ 300 mmHg, p<0.0001) and had better lung donor score values (LDS) (28% vs. 17% with LDS=6, p<0.0001) compared to donors used for LTx in countries with low donation rate. Survival rates for the groups LDS =6 and ≥7 at 5 years were 69.7% and 60.9% (p=0.007). Lung donor quality significantly impacts on long-term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized

GRIPS - Gamma-Ray Imaging, Polarimetry and Spectroscopy

We propose to perform a continuously scanning all-sky survey from 200 keV to 80 MeV achieving a sensitivity which is better by a factor of 40 or more compared to the previous missions in this energy range. The Gamma-Ray Imaging, Polarimetry and Spectroscopy (GRIPS) mission addresses fundamental questions in ESA's Cosmic Vision plan. Among the major themes of the strategic plan, GRIPS has its focus on the evolving, violent Universe, exploring a unique energy window. We propose to investigate $\gamma$-ray bursts and blazars, the mechanisms behind supernova explosions, nucleosynthesis and spallation, the enigmatic origin of positrons in our Galaxy, and the nature of radiation processes and particle acceleration in extreme cosmic sources including pulsars and magnetars. The natural energy scale for these non-thermal processes is of the order of MeV. Although they can be partially and indirectly studied using other methods, only the proposed GRIPS measurements will provide direct access to their primary photons. GRIPS will be a driver for the study of transient sources in the era of neutrino and gravitational wave observatories such as IceCUBE and LISA, establishing a new type of diagnostics in relativistic and nuclear astrophysics. This will support extrapolations to investigate star formation, galaxy evolution, and black hole formation at high redshifts.Comment: to appear in Exp. Astron., special vol. on M3-Call of ESA's Cosmic Vision 2010; 25 p., 25 figs; see also www.grips-mission.e

Impact of donor lung quality on post-transplant recipient outcome in the Lung Allocation Score era in Eurotransplant – a historical prospective study

The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤45 years, P < 0.0001), were less often smokers (35% vs. 46%, P < 0.0001), had more often clear chest X-rays (82% vs. 72%, P < 0.0001), had better donor oxygenation ratios (20% vs. 26% with PaO2/FiO2 ≤ 300 mmHg, P < 0.0001), and had better lung donor score values (LDS; 28% vs. 17% with LDS = 6, P < 0.0001) compared with donors used for LTx in countries with low donation rate. Survival rates for the groups LDS = 6 and ≥7 at 5 years were 69.7% and 60.9% (P = 0.007). Lung donor quality significantly impacts on long-term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized