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Aboveground biomass density (AGBD) estimates from Earth Observation (EO) can be presented with the consistency standards mandated by United Nations Framework Convention on Climate Change (UNFCCC). This article delivers AGBD estimates, in the format of Intergovernmental Panel on Climate Change (IPCC) Tier 1 values for natural forests, sourced from National Aeronautics and Space Administration's (NASA's) Global Ecosystem Dynamics Investigation (GEDI) and Ice, Cloud and land Elevation Satellite (ICESat-2), and European Space Agency's (ESA's) Climate Change Initiative (CCI). It also provides the underlying classification used by the IPCC as geospatial layers, delineating global forests by ecozones, continents and status (primary, young (≤20 years) and old secondary (>20 years)). The approaches leverage complementary strengths of various EO-derived datasets that are compiled in an open-science framework through the Multi-mission Algorithm and Analysis Platform (MAAP). This transparency and flexibility enables the adoption of any new incoming datasets in the framework in the future. The EO-based AGBD estimates are expected to be an independent contribution to the IPCC Emission Factors Database in support of UNFCCC processes, and the forest classification expected to support the generation of other policy-relevant datasets while reflecting ongoing shifts in global forests with climate change. [ABSTRACT FROM AUTHOR]

Tropical forest degradation from selective logging, fire and edge effects is a major driver of carbon and biodiversity loss1–3, with annual rates comparable to those of deforestation4. However, its actual extent and long-term impacts remain uncertain at global tropical scale5. Here we quantify the magnitude and persistence of multiple types of degradation on forest structure by combining satellite remote sensing data on pantropical moist forest cover changes4 with estimates of canopy height and biomass from spaceborne6 light detection and ranging (LiDAR). We estimate that forest height decreases owing to selective logging and fire by 15% and 50%, respectively, with low rates of recovery even after 20 years. Agriculture and road expansion trigger a 20% to 30% reduction in canopy height and biomass at the forest edge, with persistent effects being measurable up to 1.5 km inside the forest. Edge effects encroach on 18% (approximately 206 Mha) of the remaining tropical moist forests, an area more than 200% larger than previously estimated7. Finally, degraded forests with more than 50% canopy loss are significantly more vulnerable to subsequent deforestation. Collectively, our findings call for greater efforts to prevent degradation and protect already degraded forests to meet the conservation pledges made at recent United Nations Climate Change and Biodiversity conferences.A global survey on the magnitude and persistence of moist forest cover change and canopy height following degradation using satellite remote sensing data finds that the effects are substantial and persist for decades. [ABSTRACT FROM AUTHOR]

A magnetic field is generated to modify the effective gravity acting on settling particles in a laboratory experiment. When applied to a magnetized spherical particle settling in water-glycerol mixtures, the magnetic field produces a vertical force that counteracts the gravitational field, hence allowing for the magnetic tuning of the settling properties of the particle. While doing so, the spin of the particle around the direction perpendicular to the applied magnetic field is blocked, thus allowing spin solely around the direction of the magnetic field. This method of magnetic modification of the effective gravity is tested on the settling of spherical magnets in quiescent fluids over Galileo numbers in the range [100, 300] and a fixed particle density of 8200 kg/m 3 . The results obtained by varying the Galileo number via the magnetic modification of effective gravity are compared to those obtained with non-magnetic spheres when the Galileo number is modified by varying the fluid's viscosity. We show that the same taxonomy of settling regimes with nearly identical geometrical properties (in terms of planarity and obliqueness) of the trajectories is recovered. In addition to proving that it is possible to magnetically tame the settling of particles in fluids preserving the features of the non-magnetic case, this also reveals that blocking the spin of the particles does not produce any significant effect on its settling properties in a quiescent fluid. This novel experimental methodology opens new possibilities to experimentally explore many other subtle aspects of the coupling between settling particles and fluids (for instance, to disentangle the effects of rotation, inertia, and/or anisotropy of the particles) in more complex situations including the case of turbulent flows. [ABSTRACT FROM AUTHOR]

To evaluate the feasibility of continuous determination of the optimal mean arterial blood pressure (opt-MAP) according to cerebral autoregulation and to describe the opt-MAP, the autoregulation limits, and the time spent outside these limits in children within 48 h of cardiac surgery. Cerebral autoregulation was assessed using the correlation coefficient (COx) between cerebral oxygenation and MAP in children following cardiac surgery. Plots depicting the COx according to the MAP were used to determine the opt-MAP using weighted multiple time windows. For each patient, we estimated (1) the time spent with MAP outside the autoregulation limits and (2) the burden of deviation, defined as the area between the MAP curve and the autoregulation limits when the MAP was outside these limits. Fifty-one patients with a median age of 7.1 (IQR 0.7–52.0) months old were included. The opt-MAP was calculated for 94% (IQR 90–96) of the monitored time. The opt-MAP was significantly lower in neonates < 1 month old. The patients spent 24% (18–31) of the time outside of the autoregulation limits, with no significant differences between age groups. Continuous determination of the opt-MAP is feasible in children within the first 48 h following cardiac surgery. [ABSTRACT FROM AUTHOR]

We study the non-turbulent pipe flow of a Newtonian fluid through a confined porous medium made of randomly arranged spherical particles in the situation where the ratio between the pipe diameter over the particle diameter (D/d) is less than 10. Using experiments and numerical simulations, we examine the relation between the flow rate and the mean pressure gradient as a function of the Reynolds number and particle size, and how it is affected by the presence of the walls. We investigate the intrinsic variability of the measurements in relation to the randomness of the particle arrangement and how such variability is linked to spatial fluctuations of pressure within the bed. We observe that as D/d decreases, the pressure gradient presents a stronger variability, particularly in relation to where measurements are taken within the pipe. The study also quantifies the difference between measuring the pressure drop at the wall versus averaging over the entire volume, finding a small difference of 2.5 % at most. We examine how the mean pressure gradient is affected by the lateral walls, finding that the pressure drop follows a consistent 1/Re scaling regardless of the confinement of the bed. Finally, we observe that the pressure gradient balances the force exerted on the solid spheres with a very weak contribution of the wall friction, showing that the role of confinement corresponds to a global effect on the bed arrangement which in turns affects the mean pressure gradient. [ABSTRACT FROM AUTHOR]

Background: Levosimendan (LVSMD) is a calcium-sensitizer inotropic and vasodilator agent whose use might have a beneficial effect on the weaning of venoarterial extracorporeal membrane oxygenation (VA-ECMO). In light of LVSMD pharmacological characteristics, we hypothesized that ECMO may induce major pharmacokinetic (PK) modifications for LVSMD and its metabolites. Objective: The aim of this study was to investigate the PK of LVSMD and its metabolites, and to assess the effects of ECMO on PK parameters. Methods: We conducted a multicentric, prospective study (NCT03681379). Twenty-seven infusions of LVSMD were performed, allowing for the collection of 255 blood samples. Non-linear mixed-effects modeling software (MONOLIX®) was used to develop a parent-metabolite PK model of LVSMD and its metabolites. Results: Most patients received a 0.2 µg/kg/min infusion of LVSMD over 24 h. After elimination of non-reliable samples or concentrations below the limit of quantification, 166, 101 and 85 samples were considered for LVSMD, OR-1855 and OR-1896, respectively, of which 81, 53 and 41, respectively, were drawn under ECMO conditions. Parent-metabolite PK modeling revealed that a two-compartment model with first-order elimination best described LVSMD PK. Use of a transit compartment allowed for an explanation of the delayed appearance of circulating OR-1855 and OR-1896, with the latter following a first-order elimination. Patient weight influenced the central volume of distribution and elimination of LVSMD. ECMO support increased the elimination rate of LVSMD by 78%, and ECMO also slowed down the metabolite formation rate by 85% for OR-1855, which in turn is converted to the active metabolite OR-1896, 14% slower than without ECMO. Simulated data revealed that standard dosing may not be appropriate for patients under ECMO, with a decrease in the steady-state concentration of LVSMD and lower exposure to the active metabolite OR-1896. Conclusions: ECMO altered PK parameters for LVSMD and its metabolites. An infusion of LVSMD over 48 h, instead of 24 h, with a slightly higher dose may promote synthesis of the active metabolite OR-1896, which is responsible for the long-term efficacy of LVSMD. Further trials evaluating ECMO effects using a PK/pharmacodynamic approach may be of interest. Registration: ClinicalTrials.gov identifier number NCT03681379. [ABSTRACT FROM AUTHOR]

Heat shock proteins (HSPs) play oncogenic roles in human tumours. We reported a somatic inactivating mutation of HSP110 (HSP110DE9) in mismatch repair-deficient (dMMR) cancers displaying microsatellite instability (MSI) but did not assess its impact. We evaluated the impact of the Hsp110DE9 mutation on tumour development and the chemotherapy response in a dMMR knock-in mouse model (Hsp110DE9KIMsh2KO mice). The effect of the Hsp110DE9 mutation on tumorigenesis and survival was evaluated in Msh2KO mice that were null (Hsp110wt), heterozygous (Hsp110DE9KI/+), or homozygous (Hsp110DE9KI/KI) for the Hsp110DE9 mutation by assessing tumoral syndrome (organomegaly index, tumour staging) and survival (Kaplan–Meier curves). 5-Fluorouracil (5-FU), which is the backbone of chemotherapy regimens in gastrointestinal cancers and is commonly used in other tumour types but is not effective against dMMR cells in vivo, was administered to Hsp110DE9KI/KI, Hsp110DE9KI/+, and Hsp110wtMsh2KO mice. Hsp110, Ki67 (proliferation marker) and activated caspase-3 (apoptosis marker) expression were assessed in normal and tumour tissue samples by western blotting, immunophenotyping and cell sorting. Hsp110wt expression was drastically reduced or totally lost in tumours from Msh2KOHsp110DE9KI/+ and Msh2KOHsp110DE9KI/KI mice. The Hsp110DE9 mutation did not affect overall survival or tumoral syndrome in Msh2KOHsp110DE9KI/+ and Msh2KOHsp110DE9KI/KI mice but drastically improved the 5-FU response in all cohorts (Msh2KOHsp110DE9KI/KI: P5fu = 0.001; Msh2KOHsp110DE9KI/+: P5fu = 0.005; Msh2KOHsp110wt: P5fu = 0.335). Histopathological examination and cell sorting analyses confirmed major hypersensitization to 5-FU-induced death of both Hsp110DE9KI/KI and Hsp110DE9KI/+ dMMR cancer cells. This study highlights how dMMR tumour cells adapt to HSP110 inactivation but become hypersensitive to 5-FU, suggesting Hsp110DE9 as a predictive factor of 5-FU efficacy. [ABSTRACT FROM AUTHOR]

Human-mediated species dispersal across the Mediterranean stretches back at least 10,000 years and has left an indelible stamp on present-day biodiversity. Believed to be a descendant of the Asiatic mouflon (Ovis gmelini gmelinii), the Corsican mouflon (O. g. musimon) was translocated during the Neolithic as ancestral livestock by humans migrating from the Fertile Crescent to the Western Mediterranean. Today, two geographically limited and disconnected populations can be found in Corsica. Whether they originated from distinct founders or one ancestral population that later split remains unknown, although such information is pivotal for the species' management on the island. We genotyped 109 and 176 individuals at the Cytochrome-b gene and 16 loci of the microsatellite DNA, respectively, to gain insights into the natural history of the Corsican mouflon. We found evidence confirming that the Asiatic was the ancestor of the Corsican mouflon, which should thus be unvaryingly referred to as O. g. musimon, i.e. as a subspecies of the Asiatic mouflon. Haplotype divergence dating and the investigation of genetic structure highlighted a strong and ancient genetic differentiation between the two Corsican populations. Approximate Bayesian Computation pointed to the introduction of a single group of founders as the most reliable scenario for the origin of the entire Corsican population. Later, this ancestral stock would have decreased in number, facing genetic bottlenecks and eventually resulting in two divergent demes. Splitting most likely occurred several hundred years ago. Their shared past notwithstanding, we discuss whether the two relic Corsican mouflon populations should be now considered as distinct management units. [ABSTRACT FROM AUTHOR]

Background: Cerebral autoregulation (CA) impairment is associated with neurological complications among children supported by extracorporeal membrane oxygenation (ECMO). Severe variations of arterial CO2 (PaCO2) and O2 (PaO2) tension after ECMO onset are common and associate with mortality and poor neurological outcome. The impact of gas exchange on CA among critically ill patients is poorly studied. Methods: Retrospective analysis of data collected prospectively from 30 children treated with veno-arterial or veno-venous ECMO in the PICU of Nantes University Hospital, France. A correlation coefficient between the variations of regional cerebral oxygen saturation (rSO2) and the variations of mean arterial blood pressure (MAP) was calculated as an index of CA (cerebral oxygenation reactivity index, COx). Cox–MAP plots were investigated allowing determining lower limit of autoregulation (LLA) and upper limit of autoregulation (ULA) limits of autoregulation. Age-based normal blood pressure was used to adjust the MAP, LLA, and ULA data from each patient and then reported as percentage (nMAP, nLLA, and nULA, respectively). RSO2, COx, nMAP, nLLA, and nULA values were averaged over one hour before each arterial blood gas (ABG) sample during ECMO run. Results: Thirty children (median age 4.8 months [Interquartile range (IQR) 0.7–39.1], median weight 5 kg [IQR 4–15]) experiencing 31 ECMO runs were included in the study. Three hundred and ninety ABGs were analyzed. The highest values of COx were observed on day 1 (D1) of ECMO. The relationship between COx and PaCO2 was nonlinear, but COx values tended to be lower in case of hypercapnia compared to normocapnia. During the whole ECMO run, a weak but significant correlation between PaCO2 and nULA was observed (R = 0.432, p = 0.02). On D1 of ECMO, this correlation was stronger (R = 0.85, p = 0.03) and a positive correlation between nLLA and PaCO2 was also found (R = 0.726, p < 0.001). A very weak negative correlation between PaO2 and nULA was observed within the whole ECMO run and on D1 of ECMO (R = −0.07 p = 0.04 and R = −0.135 p = <0.001, respectively). The difference between nULA and nLLA representing the span of the autoregulation plateau was positively correlated with PaCO2 and negatively correlated with PaO2 (R = 0.224, p = 0.01 and R = −0.051, p = 0.004, respectively). Conclusions: We observed a complex relationship between PaCO2 and CA, influenced by the level of blood pressure. Hypercapnia seems to be globally protective in normotensive or hypertensive condition, while, in case of very low MAP, hypercapnia may disturb CA as it increases LLA. These data add additional arguments for very cautiously lower PaCO2, especially after ECMO start. [ABSTRACT FROM AUTHOR]

Objective: Cerebral autoregulation (CA) impairment may pose a risk factor for neurological complications among children supported by extracorporeal membrane oxygenation (ECMO). Our first objective was to investigate the feasibility of CA continuous monitoring during ECMO treatment and to describe its evolution over time. The second objective was to analyze the association between CA impairment and neurological outcome. Design: Observational prospective study. Patients and Setting: Twenty-nine children treated with veno-arterial or veno-venous ECMO in the PICU of Nantes University Hospital, France, and the PICU of the IRCCS Giannina Gaslini Institute in Genoa, Italy. Measurements: A correlation coefficient between the variations of regional cerebral oxygen saturation and the variations of mean arterial blood pressure (MAP) was calculated as an index of CA (cerebral oxygenation reactivity index, COx). A COx > 0.3 was considered as indicative of autoregulation impairment. COx—MAP plots were investigated allowing determining optimal MAP (MAPopt) and limits of autoregulation: lower (LLA) and upper (ULA). Neurological outcome was assessed by the onset of an acute neurological event (ANE) after ECMO start. Results: We included 29 children (median age 84 days, weight 4.8 kg). MAPopt, LLA, and ULA were detected in 90.8% (84.3–93.3) of monitoring time. Mean COx was significantly higher during day 1 of ECMO compared to day 2 [0.1 (0.02–0.15) vs. 0.01 (− 0.05 to 0.1), p = 0.002]. Twelve children experienced ANE (34.5%). The mean COx and the percentage of time spent with a COx > 0.3 were significantly higher among ANE+ compared to ANE− patients [0.09 (0.01–0.23) vs. 0.04 (− 0.02 to 0.06), p = 0.04 and 33.3% (24.8–62.1) vs. 20.8% (17.3–23.7) p = 0.001]. ANE+ patients spent significantly more time with MAP below LLA [17.2% (6.5–32.9) vs. 5.6% (3.6–9.9), p = 0.02] and above ULA [13% (5.3–38.4) vs. 4.2% (2.7–7.4), p = 0.004], respectively. Conclusion: CA assessment is feasible in pediatric ECMO. The first 24 h following ECMO represents the most critical period regarding CA. Impaired autoregulation is significantly more severe among patients who experience ANE. [ABSTRACT FROM AUTHOR]

Avalanche photodiodes (APDs) are well-suited for single-photon detection on quantum communication satellites as they are a mature technology with high detection efficiency without requiring cryogenic cooling. They are, however, prone to significantly increased thermal noise caused by in-orbit radiation damage. Previous work demonstrated that a one-time application of thermal annealing reduces radiation-damage-induced APD thermal noise. Here we examine the effect of cyclical proton irradiation and thermal annealing. We use an accelerated testing environment which emulates a realistic two-year operating profile of a satellite in low-Earth-orbit. We show that repeated thermal annealing is effective at maintaining thermal noise of silicon APDs within a range suitable for quantum key distribution throughout the nominal mission life, and beyond. We examine two strategies—annealing at a fixed period of time, and annealing only when the thermal noise exceeds a pre-defined limit. We find both strategies exhibit similar thermal noise at end-of-life, with a slight overall advantage to annealing conditionally. We also observe that afterpulsing probability of the detector increases with cumulative proton irradiation. This knowledge helps guide design and tasking decisions for future space-borne quantum communication applications. [ABSTRACT FROM AUTHOR]

A pile of grains, even when at rest in a silo, can display fascinating properties. One of the most celebrated is the Janssen effect, named after the pioneering engineer who explained the pressure saturation at the bottom of a container filled with corn. This surprising behavior arises because of frictional interactions between the grains through a disordered network of contacts, and the vessel lateral walls, which partially support the weight of the column, decreasing its apparent mass. Here, we demonstrate control over frictional interactions using ferromagnetic grains and an external magnetic field. We show that the anisotropic pairwise interactions between magnetized grains result in a radial force along the walls, whose amplitude and direction is fully determined by the applied magnetic field. Such magnetic Janssen effect allows for the fine tuning of the granular column apparent mass. Our findings pave the way towards the design of functional jammed materials in confined geometries, via a further control of both their static and dynamic properties. The Janssen effect refers to the saturation of the apparent mass of a column of granular material, due to friction with the boundary of the column. Here, using ferromagnetic beads, Thorens et al. succeed in controlling the apparent mass of the column via an applied magnetic field. [ABSTRACT FROM AUTHOR]

In polygynous ungulates, males invest time and energy to reproductive activities during the rut and this involvement is expected to increase with age due to different mating tactics in young versus adult males. In contrast, mating period is expected to be less costly for females for which late gestation and lactation are the most energetically demanding periods. However, empirical supports of these hypotheses through direct measures of reproductive effort are still limited in ungulate species, particularly in males. In addition, this general pattern may be modified in populations facing selective harvesting on adult males, where young males may experience less competition to mate and invest more energy during the rut. We investigated these hypotheses by studying the age- and sex-specific variations of kidney fat reserves from pre- to post-rut periods in a trophy-hunted population of Mediterranean mouflon (Ovis gmelini musimon × Ovis sp.), a polygynous dimorphic mountain ungulate. Females were found to build up energy from the pre-rut to the post-rut periods, most likely to face with the subsequent costs of gestation/lactation that occur few months later. Conversely, kidney fat mass strongly decreased similarly in both young and mature males, and with the same magnitude, suggesting a strong investment of males of all ages in this population. This might be related to the selective hunting pressure on mature males this population is facing with. This result supports the need for more empirical and comparative studies to better grasp the influence of trophy hunting on reproductive effort in male ungulates. [ABSTRACT FROM AUTHOR]

We present the results of the first series of successful two-way laser ranging experiments from a ground station, the Lunar Laser Ranging (LLR) station in Grasse, France, to a spacecraft at lunar distance, the Lunar Reconnaissance Orbiter (LRO). A 15 × 18 × 5 cm, 650-g array of twelve 32-mm diameter solid corner cubes is mounted on its anti-nadir deck. Ranging to this small retro-reflector array onboard a lunar orbiter from a ground station was a challenge compared to ranging to larger lunar surface retro-reflectors. Grasse measured 67 returns in two 6-min sessions on September 4, 2018. Clear returns were also recorded during two additional sessions on August 23–24, 2019 for which active slewing by LRO was performed to bring the array in view of the station. The measured echos yielded range residuals less than 3 cm (two-way time-of-flight RMS < 180 ps) relative to the reconstructed LRO trajectory. This experiment provides a new method of verifying theories of dust accumulation over decades on the lunar surface. It also showed that the use of similar arrays onboard future lunar landers and orbiters can support LLR lunar science goals, particularly with landing sites near the lunar limbs and poles, which would have better sensitivity to lunar orientation. [ABSTRACT FROM AUTHOR]

To date, efforts to reduce hospital readmissions have centered largely on hospitals. In a recently published environmental scan, we examined the literature focusing on primary care-based efforts to reduce readmissions. While rigorous studies on interventions arising from primary care are limited, we found that multi-component care transitions programs that are initiated early in the hospitalization and are part of broader primary care practice transformation appear most promising. However, policy changes are necessary to spur innovation and support effective primary care-led transitions interventions. Though more rigorous research is needed, our findings suggest that primary care can and should lead future efforts for reducing hospital readmissions. [ABSTRACT FROM AUTHOR]

Background: Phospholipases D1 and D2 (PLD1/2) are implicated in tumorigenesis through their generation of the signalling lipid phosphatidic acid and its downstream effects. Inhibition of PLD1 blocks prostate cell growth and colony formation. Here a role for PLD2 in prostate cancer (PCa), the major cancer of men in the western world, is examined. Methods: PLD2 expression was analysed by immunohistochemistry and western blotting. The effects of PLD2 inhibition on PCa cell viability and cell motility were measured using MTS, colony forming and wound-healing assays. Results: PLD2 protein is expressed about equally in luminal and basal prostate epithelial cells. In cells from different Gleason-scored PCa tissue PLD2 protein expression is generally higher than in non-tumorigenic cells and increases in PCa tissue scored Gleason 6–8. PLD2 protein is detected in the cytosol and nucleus and had a punctate appearance. In BPH tissue stromal cells as well as basal and luminal cells express PLD2. PLD2 protein co-expresses with chromogranin A in castrate-resistant PCa tissue. PLD2 inhibition reduces PCa cell viability, colony forming ability and directional cell movement. Conclusions: PLD2 expression correlates with increasing Gleason score to GS8. PLD2 inhibition has the potential to reduce PCa progression. [ABSTRACT FROM AUTHOR]

The modulation by amino acids of muscle secretome is largely unknown. In this study, we investigate the effect of hyperaminoacidemia or specific amino acids (citrulline or leucine) on protein synthesis and secretome in myotubes. All conditions stimulate muscle protein synthesis, and secretome is differently modulated depending of the amino acids considered. In conclusion, the activation of protein synthesis by amino acids induces different modulations of the muscle secretome, proposing a new role of amino acids in the regulation of muscle function. [ABSTRACT FROM AUTHOR]

Only a few sites on Earth are technically equipped to carry out Lunar Laser Ranging (LLR) to retroreflector arrays on the surface of the Moon. Despite the weak signal, they have successfully provided LLR range data for about 49 years, generating about 26,000 normal points. Recent system upgrades and new observatories have made millimeter-level range accuracy achievable. Based on appropriate modeling and sophisticated data analysis, LLR is able to determine many parameters associated with Earth–Moon dynamics, involving the lunar ephemeris, lunar physics, the Moon's interior, reference frames and Earth orientation parameters. LLR has also become one of the strongest tools for testing Einstein's theory of general relativity in the solar system. By extending the standard solution, it is possible to solve for parameters related to gravitational physics, like the temporal variation of the gravitational constant, metric parameters as well as the strong equivalence principle, preferred-frame effects and standard-model extensions. This paper provides a review about LLR measurement and analysis. After a short historical overview, we describe the key findings of LLR, the apparatus and technologies involved, the requisite modeling techniques, some recent results and future prospects on all fronts. We expect continued improvements in LLR, maintaining its lead in contributing to science. [ABSTRACT FROM AUTHOR]

Purpose: Tumescent lidocaine anesthesia (TLA) is an opportunity to perform mastectomy for breast cancer without general anesthesia in elderly women. Few reports are available on the pharmacokinetics of lidocaine in a context of TLA during a unilateral mastectomy. The aim of this study was to describe lidocaine pharmacokinetics in elderly women undergoing breast cancer surgery after TLA and to explore the risk of the toxicity of this technique.Methods: A prospective study was conducted to examine the pharmacokinetics of lidocaine in women undergoing TLA. TLA consists of an intradermal lidocaine instillation (20 mL, 1% [200 mg]) followed by a tumescent lidocaine infiltration (100 mL of 1% lidocaine [1000 mg] and 0.5 mg epinephrine to 1 L Ringer’s lactate) via an infusion pump. A population pharmacokinetic (popPK) analysis was performed using the nonlinear mixed effects model (NONMEM).Results: The analysis included 116 observations from 17 women with a median (range) age of 83.4 (60.5-90.0). The median tumescent lidocaine dose was 800 mg (range 375-1000 mg) infused over 48.0 ± 11.0 min. A one-compartment disposition model with first order absorption, two input compartments, and a central elimination best described the pharmacokinetics of lidocaine. The estimates (between subject variability; relative standard error, %) of apparent volume, apparent clearance, tumescent absorption rate, and instillation absorption rate were 195.0 (46.3; 14.5%) L, 24.7 (48.9; 13.3%) L h−1, 0.28 (39.6; 13.8%) h−1, and 2.56 (135.3; 44.9%) h−1, respectively.Conclusions: This is the first popPK model developed to describe kinetic profiles of TLA. These findings confirm the slow diffusion of lidocaine from the tumescent deposit. [ABSTRACT FROM AUTHOR]

Context: In natural populations, gene flow often represents a key factor in determining and maintaining genetic diversity. In a worldwide context of habitat fragmentation, assessing the relative contribution of landscape features to gene flow thus appears crucial for sustainable management of species.Objective: We addressed this issue in Mediterranean mouflon (Ovis gmelini musimon × Ovis sp.) by combining previous knowledge on behavioral ecology with landscape genetics. We also assessed how sex-specific behavioral differences translated in term of functional connectivity in both sexes.Methods: We relied on 239 individuals genotyped at 16 microsatellite markers. We applied a model optimization approach in a causal modeling framework of landscape genetics to test for the effects on gene flow of habitat types and linear landscape features previously identified as important for movements and habitat selection in both sexes. Five resistance values were alternately assigned to these landscape characteristics leading to a comprehensive set of resistance surfaces.Results: Isolation by resistance shaped female gene flow, supporting the central role of linear landscape features as behavioral barriers for animal movements. Conversely, no isolation by resistance was detected in males. Although a lack of statistical power cannot be discarded to explain this result, it tended to confirm that males are less influenced by landscape structures during the mating period.Conclusions: Combining previous knowledge on behavioral ecology with results from landscape genetics was decisive in assessing functional landscape connectivity in both sexes. These results highlighted the need to perform sex-specific studies for management and conservation of dimorphic species. [ABSTRACT FROM AUTHOR]

The adhesion properties of 14 Streptococcus salivarius strains to mucus (HT29-MTX) and non-mucus secreting (Caco-2/TC7) human intestinal epithelial cells were investigated. Ability to adhere to these two eukaryotic cell lines greatly differs between strains. The presence of mucus played a major factor in adhesion, likely due to high adhesiveness to mucins present in the native human mucus layer covering the whole cell surface. Only one S. salivarius strain (F6-1), isolated from the feces of a healthy baby, was found to strongly adhere to HT-29 MTX cells at a level comparable to that of Lactobacillus rhamnosus GG, a probiotic strain considered to be highly adherent. By sequencing the genome of F6-1, we were able to identify 36 genes encoding putative surface proteins. Deletion mutants were constructed for six of them and their adhesion abilities on HT-29 MTX cells were checked. Our study confirmed that four of these genes encode adhesins involved in the adhesion of S. salivarius to host cells. Such adhesins were also identified in other S. salivarius strains. [ABSTRACT FROM AUTHOR]

Monocyte HLA-DR expression has been reported as a marker of immunosuppression and a predictor of sepsis development. However, to date, there is no report on monocyte HLA-DR monitoring exclusively in neonates (< 28 days of life) who underwent cardiac surgery under cardiopulmonary bypass (CPB), which have a high risk of nosocomial infection. In this pilot study, we studied nine neonates with a diagnosis of congenital heart disease requiring surgery under CPB. There was a significant reduction in monocyte HLA-DR expression for the first two postoperative days, as compared to preoperatively ( p = 0.004). Moreover, neonates who displayed an episode of NI had a dramatically lower HLA-DR expression at day 4, as compared to neonates without NI (4257 AB/c [2220-5895] vs 14,947 AB/c [9858-16,960]; p = 0.04). Our preliminary results could indicate that HLA-DR expression may be a useful biomarker of immunosuppression-induced secondary infection after CPB in neonates. [ABSTRACT FROM AUTHOR]

Avalanche photodiodes (APDs) are a practical option for space-based quantum communications requiring single-photon detection. However, radiation damage to APDs significantly increases their dark count rates and thus reduces their useful lifetimes in orbit. We show that high-power laser annealing of irradiated APDs of three different models (Excelitas C30902SH, Excelitas SLiK, and Laser Components SAP500S2) heals the radiation damage and several APDs are restored to typical pre-radiation dark count rates. Of nine samples we test, six APDs were thermally annealed in a previous experiment as another solution to mitigate the radiation damage. Laser annealing reduces the dark count rates further in all samples with the maximum dark count rate reduction factor varying between 5.3 and 758 when operating at ${-}80^{\circ}\mathrm{C}$ . This indicates that laser annealing is a more effective method than thermal annealing. The illumination power to reach these reduction factors ranges from 0.8 to 1.6 W. Other photon detection characteristics, such as photon detection efficiency, timing jitter, and afterpulsing probability, fluctuate but the overall performance of quantum communications should be largely unaffected by these variations. These results herald a promising method to extend the lifetime of a quantum satellite equipped with APDs. [ABSTRACT FROM AUTHOR]

Single-photon detectors in space must retain useful performance characteristics despite being bombarded with sub-atomic particles. Mitigating the effects of this space radiation is vital to enabling new space applications which require high-fidelity single-photon detection. To this end, we conducted proton radiation tests of various models of avalanche photodiodes (APDs) and one model of photomultiplier tube potentially suitable for satellite-based quantum communications. The samples were irradiated with 106 MeV protons at doses approximately equivalent to lifetimes of 0.6 , 6, 12 and 24 months in a low-Earth polar orbit. Although most detection properties were preserved, including efficiency, timing jitter and afterpulsing probability, all APD samples demonstrated significant increases in dark count rate (DCR) due to radiation-induced damage, many orders of magnitude higher than the 200 counts per second (cps) required for ground-to-satellite quantum communications. We then successfully demonstrated the mitigation of this DCR degradation through the use of deep cooling, to as low as $-86^{\circ}\mbox{C}$ . This achieved DCR below the required 200 cps over the 24 months orbit duration. DCR was further reduced by thermal annealing at temperatures of +50 to $+100^{\circ}\mbox{C}$ . [ABSTRACT FROM AUTHOR]

To increase software performance, it is now common to use hardware accelerators. Currently, GPUs are the most widespread accelerators that can handle general computations. This requires to use GPGPU frameworks such as Cuda or OpenCL. Both are very low-level and make the benefit of GPGPU programming difficult to achieve. In particular, they require to write programs as a combination of two subprograms, and, to manually manage devices and memory transfers. This increases the complexity of the overall software design. The idea we develop in this paper is to guarantee expressiveness and safety for CPU and GPU computations and memory managements with high-level data-structures and static type-checking. In this paper, we present how statically typed languages, compilers and libraries help harness high level GPGPU programming. In particular, we show how we added high-level user-defined data structures to a GPGPU programming framework based on a statically typed programming language: OCaml. Thus, we describe the introduction of records and tagged unions shared between the host program and GPGPU kernels described via a domain specific language as well as a simple pattern matching control structure to manage them. Examples, practical tests and comparisons with state of the art tools, show that our solutions improve code design, productivity, and safety while providing a high level of performance. [ABSTRACT FROM AUTHOR]

Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. B Correction to: Neurocrit Care (2021) 35(2):480-490 b https://doi.org/10.1007/s12028-021-01201-8 The original article has been updated to correct the author name Andrea Moscatelli. [Extracted from the article]

B Correction to: Neurocrit Care (2021) 34:935-945 b https://doi.org/10.1007/s12028-020-01111-1 The original article has been updated to correct the author name Andrea Moscatelli. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. [Extracted from the article]

Objective: To determine the independent risk factors for late-onset ventilator-associated pneumonia (VAP) in trauma patients receiving selective digestive decontamination (SDD).Design: A 4-year, prospective cohort study of trauma patients meeting the following criteria: injury severity score >15, and duration of mechanical ventilation >5 days. Predictors of late-onset VAP occurrence were assessed by logistic regression analysis.Population: All patients received SDD consisting of polymixin E, gentamicin, and amphotericin B applied in nostrils, mouth, and gut with a 3-day course of parenteral cefazolin. VAP was suspected on clinical and radiological signs, and confirmed by the presence of at least one microorganism at a concentration of at least 10(4) CFU/ml on the broncho-alveolar lavage.Measurement: Independent risk factors for late-onset VAP.Results: A late-onset VAP was diagnosed in 90 (56%) out of 159 patients. Predicting factors for late-onset VAP were: use of non-depolarizing muscle relaxant agents for intubation [3.4 (CI 1.08-10.73)], duration of intubation [1.06 (CI 1.01-1.17)], length of intensive care unit (ICU) stay [1.05 (CI 1.02-1.09)], and prior tracheal colonization [1.03 (CI 1.02-1.21)]. Exposure to prior antimicrobial treatment, except SDD, conferred protection [0.3 (0.12-0.74)].Conclusion: This study confirms the role of duration of intubation, length of ICU stay, and prior tracheal colonization in the development of late-onset VAP. The results also highlight the importance of the initial management on the development of late-onset VAP. The type of neuromuscular blocking agents to intubate trauma patients should be evaluated in future studies. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1007/s40262-022-01199-y. B Correction to: Clinical Pharmacokinetics b https://doi.org/10.1007/s40262-022-01199-y In this article the author name Mehdi Oualha was incorrectly written as Mehdi Ouahla. [Extracted from the article]

This is the first substrate-borne communication record of the troglobitic planthopper Typhlobrixia namorokensis in the caves of the Ambovonomby network, Namoroka Tsingy, Madagascar. A supplementary morphological description of the male genitalia is provided and, for the first time, female genitalia of T. namorokensis are characterized. Molecular data were obtained for T. namorokensis; molecular analysis also reveals the presence of another (yet unidentified) cavernicolous cixiid in the Antsifotra caves network. The evolutionary origin of T. namorokensis is discussed. Its adaptation to caves and its behaviour allows its identification as a true troglobiont. Its vibrational signal structure is compared to the calls of other cave-dwelling cixiids. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid (LPA) is a lipid-derived signaling molecule that plays key roles in diverse biological processes including inflammation and uterine remodeling. Although the function of LPA and its receptors has been extensively studied using knock-out mice, the temporal-spatial expression of LPA receptors is less well-characterized. To gain further insight into the dynamic regulation of LPA receptor 3 (Lpar3) expression in vivo by bioluminescence imaging, we generated and characterized mice transgenic for a putative Lpar3 promoter fragment. A non-coding region of the Lpar3 gene immediately upstream of the start site was subcloned adjacent to the luciferase gene. Promoter activity was determined by in vitro luciferase assays, in vivo bioluminescent imaging or by semi-quantitative real-time PCR. The air-pouch model was used to investigate Lpar3 promoter activity in the context of inflammation. The putative Lpar3 promoter fragment behaved similarly to the endogenous promoter in vitro and in vivo. In male mice, elevated levels of Lpar3-induced luciferase activity were observed in the testis. In female mice, the basal level of luciferase activity in the uterus significantly increased during pseudopregnancy. Moreover, luciferase activity was upregulated by TNF-α in the air-pouch model. We report the identification of a functional Lpar3 promoter fragment and the generation of a transgenic mouse model to investigate the regulation of Lpar3 promoter activity non-invasively in vivo by bioluminescence imaging. This mouse model is a valuable tool for reproductive biology and inflammation research as well as other biological processes in which this receptor is involved. [ABSTRACT FROM AUTHOR]

Following recent advances in the morphological interpretations of the tegmen basal cell margins in the Paraneoptera, a standardized and homology-driven groundplan terminology for tegmina types, structures and vein patterns in Hemiptera Fulgoromorpha, including fossils, is proposed. Each term is listed with a morphological definition, compared and linked to the main systems of planthopper forewing description that have been reviewed. The importance of a standardized and homology-driven terminology is stressed to enhance the quality of data in taxonomic descriptions and to strengthen phylogenetic morphological analysis results. When the interpretation of the origin of vein branches is render difficult, a three-step strategy for pattern recognition of the vein is proposed based on two principles: (1) vein forks are more informative than topology of the vein branches: a search for homologous areas, the nodal cells in particular, must first guide the recognition rather the number of branches of a vein, and (2) minimum of ad hoc evolutionary events should be invoked in the understanding of a modified vein pattern. Examples of some conflicting interpretations of venation patterns in planthoppers are discussed within different families for both extant and extinct taxa. For the first time, the concept of brachypterism is defined in a non-relative way independently from other structures, and the new one of hyperpterism is proposed; a reporting system is proposed for each of them. [ABSTRACT FROM AUTHOR]

Rationale and objectives: Recognition memory is an important aspect of human declarative memory and is one of the routine memory abilities altered in patients with amnestic syndrome and Alzheimer's disease. In rodents, recognition memory has been most widely assessed using the novel object preference paradigm, which exploits the spontaneous preference that animals display for novel objects. Here, we used nose-poke units instead of objects to design a simple automated method for assessing context recognition memory in mice. Methods: In the acquisition trial, mice are exposed for the first time to an operant chamber with one blinking nose-poke unit. In the choice session, a novel nonblinking nose-poke unit is inserted into an empty spatial location and the number of nose poking dedicated to each set of nose-poke unit is used as an index of recognition memory. Results: We report that recognition performance varies as a function of the length of the acquisition period and the retention delay and is sensitive to conventional amnestic treatments. By manipulating the features of the operant chamber during a brief retrieval episode (3-min long), we further demonstrate that reconsolidation of the original contextual memory depends on the magnitude and the type of environmental changes introduced into the familiar spatial environment. Conclusions: These results show that the nose-poke recognition task provides a rapid and reliable way for assessing context recognition memory in mice and offers new possibilities for the deciphering of the brain mechanisms governing the reconsolidation process. [ABSTRACT FROM AUTHOR]

General purpose (GP)GPU programming demands to couple highly parallel computing units with classic CPUs to obtain a high performance. Heterogenous systems lead to complex designs combining multiple paradigms and programming languages to manage each hardware architecture. In this paper, we present tools to harness GPGPU programming through the high-level OCaml programming language. We describe the SPOC library that allows to handle GPGPU subprograms (kernels) and data transfers between devices. We then present how SPOC expresses GPGPU kernel: through interoperability with common low-level extensions (from Cuda and OpenCL frameworks) but also via an embedded DSL for OCaml. Using simple benchmarks as well as a real world HPC software, we show that SPOC can offer a high performance while efficiently easing development. To allow better abstractions over tasks and data, we introduce some parallel skeletons built upon SPOC as well as composition constructs over those skeletons. [ABSTRACT FROM AUTHOR]

An essential task of participatory action-research is to help close the policy implementation gap that leads to large discrepancies between policy frameworks and local practices. Too often, official regulations, laws and decrees fail to translate into concrete action on the ground. Loose institutional linkages between research, extension and local communities are often blamed as the main culprits for this gap. In turn, many stakeholders call for enhanced participation as a way to bring together scientists, development practitioners and local communities in negotiating competing claims for natural resources and designing realistic pathways towards sustainable development. Despite such general consensus about the value of participation, the latter cannot be decreed nor imposed. Participation is an emerging quality of collective-action and social-learning processes. In this paper, the experience of participatory land-use planning conducted in Laos serves to illustrate a model of the science-practice-policy interface that was developed to facilitate the interactions between three groups of stakeholders, i.e. scientists, planners and villagers, in designing future landscapes. Emphasis was put on developing an approach that is generic and adaptive enough to be applied nationally while engaging local communities in context-sensitive negotiations. The set of tools and methods developed through action-research contributed to enhanced communication and participation from initial consultation and cooperation stages towards collective decision-making and action. Both the activity of landscape design and the resulting patterns can be improved by incorporating landscape science in strategic multi-stakeholder negotiations. [ABSTRACT FROM AUTHOR]

Quantum correlations, often observed as violations of Bell inequalities, are critical to our understanding of the quantum world, with far-reaching technological and fundamental impact. Many tests of Bell inequalities have studied pairs of correlated particles. However, interest in multi-particle quantum correlations is driving the experimental frontier to test larger systems. All violations to date require supplementary assumptions that open results to loopholes, the closing of which is one of the most important challenges in quantum science. Seminal experiments have closed some loopholes, but no experiment has closed locality loopholes with three or more particles. Here, we close both the locality and freedom-of-choice loopholes by distributing three-photon Greenberger-Horne-Zeilinger entangled states to independent observers. We measured a violation of Mermin's inequality with parameter 2.77 ± 0.08, violating its classical bound by nine standard deviations. These results are a milestone in multi-party quantum communication and a significant advancement of the foundations of quantum mechanics. [ABSTRACT FROM AUTHOR]

Internal morphological structures of Cixiidae mouthparts are described and compared in various representatives of the Cixiidae and several other representatives of hemipterans. The morphological study shows that the mouthpart structures have not evolved uniformly and reveals the great disparity of these structures. Particularly, the connecting system of the mouthparts, localisation of salivary canal and shape of the mandibular and maxillar stylets provide together a new set of 17 new characters. A parsimonious analysis to evaluate the phylogenetic interest carried by these 17 selected characters shows that mouthpart structures have not evolved anarchically, but that they indeed carry some phylogenetic information that will be useful to be included in further morphological phylogenetic analysis. [ABSTRACT FROM AUTHOR]

The Eumetabola (Endopterygota (also known as Holometabola) plus Paraneoptera) have the highest number of species of any clade, and greatly contribute to animal species biodiversity. The palaeoecological circumstances that favoured their emergence and success remain an intriguing question. Recent molecular phylogenetic analyses have suggested a wide range of dates for the initial appearance of the Holometabola, from the Middle Devonian epoch (391 million years (Myr) ago) to the Late Pennsylvanian epoch (311 Myr ago), and Hemiptera (310 Myr ago). Palaeoenvironments greatly changed over these periods, with global cooling and increasing complexity of green forests. The Pennsylvanian-period crown-eumetabolan fossil record remains notably incomplete, particularly as several fossils have been erroneously considered to be stem Holometabola (Supplementary Information); the earliest definitive beetles are from the start of the Permian period. The emergence of the hymenopterids, sister group to other Holometabola, is dated between 350 and 309 Myr ago, incongruent with their current earliest record (Middle Triassic epoch). Here we describe five fossils- a Gzhelian-age stem coleopterid, a holometabolous larva of uncertain ordinal affinity, a stem hymenopterid, and early Hemiptera and Psocodea, all from the Moscovian age-and reveal a notable penecontemporaneous breadth of early eumetabolan insects. These discoveries are more congruent with current hypotheses of clade divergence. Eumetabola experienced episodes of diversification during the Bashkirian-Moscovian and the Kasimovian-Gzhelian ages. This cladogenetic activity is perhaps related to notable episodes of drying resulting from glaciations, leading to the eventual demise in Euramerica of coal-swamp ecosystems, evidenced by floral turnover during this interval. These ancient species were of very small size, living in the shadow of Palaeozoic-era 'giant' insects. Although these discoveries reveal unexpected Pennsylvanian eumetabolan diversity, the lineage radiated more successfully only after the mass extinctions at the end of the Permian period, giving rise to the familiar crown groups of their respective clades. [ABSTRACT FROM AUTHOR]

The present paper describes the sensory structures on the apical segment of the labium in fifteen fulgoromorphan families (Hemiptera: Fulgoromorpha), using the scanning electron microscope. Thirteen morphologically distinct types of sensilla are identified: five types of multiporous sensilla, four types of uniporous sensilla and four types of nonporous sensilla. Three subapical sensory organ types are also recognized, formed from one to several sensilla, each characteristic of a family group. Sensilla chaetica (mechanoreceptive sensilla) fall into three categories dependent on length and are numerous and evenly distributed on the surface of the labium except where they occur on specialized sensory fields. The planthopper morphological ground plan is represented by two apical pair of sensory fields (dorsal and ventral) on which 11 dorsal pairs of sensilla (10 peg-like pairs + 1 specialized pair dome or cupola-like) and 2 ventral pairs of sensilla basiconica occur. Two main patterns (cixiid and issid) together with more specialized ones (derbid, lophopid, flatid and fulgorid) are reported. Disparity and diversity of the sensory structures are analyzed from a taxonomic and functional perspective. A gustatory function is provided for several chemoreceptive labial sensilla, as in the antennal flagellum sensilla in some other Hemiptera. This represents a more recently evolved function for the planthopper labium. Finally, further lines of study are suggested for future work on the phylogeny of the group based on the studied characters. [ABSTRACT FROM AUTHOR]