The 2021 SIIM-FISABIO-RSNA Machine Learning COVID-19 Challenge: Annotation and Standard Exam Classification of COVID-19 Chest Radiographs.

We describe the curation, annotation methodology, and characteristics of the dataset used in an artificial intelligence challenge for detection and localization of COVID-19 on chest radiographs. The chest radiographs were annotated by an international group of radiologists into four mutually exclusive categories, including "typical," "indeterminate," and "atypical appearance" for COVID-19, or "negative for pneumonia," adapted from previously published guidelines, and bounding boxes were placed on airspace opacities. This dataset and respective annotations are available to researchers for academic and noncommercial use.

An extremely high-altitude plume seen at Mars' morning terminator.

The Martian limb (that is, the observed 'edge' of the planet) represents a unique window into the complex atmospheric phenomena occurring there. Clouds of ice crystals (CO2 ice or H2O ice) have been observed numerous times by spacecraft and ground-based telescopes, showing that clouds are typically layered and always confined below an altitude of 100 kilometres; suspended dust has also been detected at altitudes up to 60 kilometres during major dust storms. Highly concentrated and localized patches of auroral emission controlled by magnetic field anomalies in the crust have been observed at an altitude of 130 kilometres. Here we report the occurrence in March and April 2012 of two bright, extremely high-altitude plumes at the Martian terminator (the day-night boundary) at 200 to 250 kilometres or more above the surface, and thus well into the ionosphere and the exosphere. They were spotted at a longitude of about 195° west, a latitude of about -45° (at Terra Cimmeria), extended about 500 to 1,000 kilometres in both the north-south and east-west directions, and lasted for about 10 days. The features exhibited day-to-day variability, and were seen at the morning terminator but not at the evening limb, which indicates rapid evolution in less than 10 hours and a cyclic behaviour. We used photometric measurements to explore two possible scenarios and investigate their nature. For particles reflecting solar radiation, clouds of CO2-ice or H2O-ice particles with an effective radius of 0.1 micrometres are favoured over dust. Alternatively, the plume could arise from auroral emission, of a brightness more than 1,000 times that of the Earth's aurora, over a region with a strong magnetic anomaly where aurorae have previously been detected. Importantly, both explanations defy our current understanding of Mars' upper atmosphere.

Silver nanoflower-coated paper as dual substrate for surface-enhanced Raman spectroscopy and ambient pressure mass spectrometry analysis.

Paper-based analytical devices (PADs) have encountered a wealth of applications in recent years thanks to the numerous advantages of paper as a support. A silver nanoflower (AgNF) modified paper-based dual substrate for both surface-enhanced Raman spectroscopy (SERS) and ambient pressure paper spray mass spectrometry (PS-MS) was developed. AgNFs were immobilized on nylon-coated paper modified with silver and ethylenediamine. The developed substrate was characterized via scanning electron microscopy and infrared spectroscopy. The densely packed nanoscale petals of the AgNFs lead to a large number of so-called hot spots at their overlapping points, which result in an enhancement of the Raman signal. In addition, the presence of the AgNFs produces an increase in the sensitivity of the mass spectrometric analysis as compared with bare paper and nylon/Ag-coated paper. The dual substrate was evaluated for the identification and quantification of ketoprofen in aqueous standards as well as human saliva from healthy volunteers. The method enables the determination of ketoprofen with a limit of detection and limit of quantification via PS-MS of 0.023 and 0.076 mg L-1, respectively, with a relative standard deviation (RSD) of 3.4% at a concentration of 0.1 mg L-1. This dual substrate enables the simple and fast detection of ketoprofen with minimal sample preparation, providing complementary Raman and mass spectrometric information. Graphical abstract.

Physicochemical and microbiological stability of two news oral liquid formulations of clonidine hydrochloride for pediatric patients.

Pediatric patients present changing physiological features. Because of the lack of land suitable for commercial management, pediatric specialties very often need to prepare extemporaneous formulations to improve the dosage and administration of drugs for children. Oral liquid formulations are the most suitable for pediatric patients. Clonidine is widely used in the pediatric population for opioid withdrawal, hypertensive crisis, attention deficit disorders and hyperactivity syndrome, and as an analgesic in neuropathic cancer pain. The objective was to study the physicochemical and microbiological stability and determine the shelf life of an oral solution containing 20 µg/mL clonidine hydrochloride in different storage conditions (5 ± 3 °C, 25 ± 3 °C, and 40 ± 2 °C). Using raw material with excipients safe for all pediatric age groups, two oral liquid formulations of clonidine hydrochloride were designed (with and without preservatives). Solutions stored at 5 ± 3 °C (with and without preservatives) were physically and microbiologically stable for at least 90 days in closed containers and for 42 days after opening. Two oral solutions of clonidine hydrochloride 20 µg/mL were developed for pediatric use from raw materials that are readily available and easy to process, containing safe excipients that are stable over a long period of time.

Selective synthesis of turbostratic polyhedral carbon nano-onions by arc discharge in water.

Carbon nano-onions (CNOs), in their spherical or polyhedral forms, represent an important class of nanomaterials, due to their peculiar physical and electrochemical properties. Among the different methods of production, arc discharge between graphite electrodes sustained by deionized water is one of the most promising to obtain good quality CNOs in gram quantities. We applied the method with the aim to optimize the production of CNOs, using an innovative experimental arrangement. The discharges generate dispersed nanomaterials and a black hard cathodic deposit, which were studied by transmission electron microscopy-high-resolution TEM, scanning electron microscopy, Raman, thermogravimetric analysis and energy-dispersive x-ray spectroscopy. A simple mechanical grinding of the deposits permitted us to obtain turbostratic polyhedral CNOs that exhibited higher stability towards burning in air, compared to CNOs found in water. We propose a mechanism for the formation of the CNOs present in the deposit, in which the crystallization is driven by a strong temperature gradient existing close to the cathode surface at the beginning of the process, and subsequently close to the deposit surface whenever it is growing.

Tunable Polarity Carbon Fibers, a Holistic Approach to Environmental Protection.

The pollution of environmental resources is an issue of social concern worldwide. Chemistry is essential for the design of decontamination strategies and analytical approaches to detect and monitor the contamination. Sorptive materials are usually required in both approaches and green synthesis should be used to minimize their own environmental impact. Carbon fibers (CFs) obtained by the pyrolysis of natural cellulose-rich materials fulfill these requirements. In this article, thirty CFs obtained under different conditions are chemically characterized and their sorption ability towards selected pollutants, covering a wide range of polarity, is evaluated. This study provides more profound knowledge related to the polarity of these materials, their interactions with chemical substances and allows the prediction of more appropriate materials (pyrolysis temperature and time) in order to remove the given pollutant. Furthermore, the use of CFs as sorptive materials for the extraction of contaminants from water samples to assist with their instrumental detection is outlined. In this sense, the use of CFs and gas chromatography with mass spectrometric detection allows the detection of selected pollutants in the low ng/mL range. Thus, this article provides an integrated approach to the potential of CFs for environmental protection.

Cytogenetic effects of Jacareubin from Calophyllum brasiliense on human peripheral blood mononucleated cells in vitro and on mouse polychromatic erythrocytes in vivo.

Jacareubin is a xanthone isolated from the heartwood of Calophyllum brasiliense with antibacterial and gastroprotective properties and the intention for clinical use as an anti-cancer treatment (due to the similar chemical structure to other anti-neoplastic drugs) requires an investigation of whether this compound can generate adverse effects on non-transformed cells. Jacareubin (0.5-1000µM in DMSO) was more cytotoxic on phytohemagglutinin (PHA)-stimulated normal human peripheral blood mononuclear cells (PBMCs; IC50 at 72h by MTT: 85.9µM) than on G0 phase-PBMCs (IC50 315.6µM) using trypan blue exclusion and formazan metabolism assays. Jacareubin had lower toxicity on PBMCs than Taxol (1µM). Jacareubin presented cytostatic activity because it inhibited PHA-stimulated PBMCs proliferation (from 2.5µM; CFSE dilution and replication index). Jacareubin induced PBMCs arrest in G0/G1 phase of the cell cycle (from 5µM) as evaluated by DNA content. Moreover, Jacareubin generated genotoxicity by breaking DNA strands selectively in PHA-stimulated PBMCs (from 5µM) rather than on resting PBMCs using the single-cell gel electrophoresis assay and increasing the frequency of micronucleated (MN) PBMCs in vitro (from 5µM) and frequency of hypodiploid cells (from 10µM). When 100mg/kg Jacareubin was injected i.p. into mice (a fifth of the LD50; 0.548g/kg. Approximately to 300µM in vitro), we observe no increase in the MN level in bone marrow cells. Jacareubin can be consider for further anti-tumoural activity due to its preferential genotoxic, cytotoxic and cytostatic actions on proliferating cells rather than on resting cells and the lack of in vivo genotoxicity.

Specific Ion Effects and pH Dependence on the Interaction Forces between Polystyrene Particles.

Colloidal interactions have been extensively studied due to the wide number of applications where colloids are present. In general, the electric double layer force and the van der Waals interaction dominate the net force acting between two colloids at large separation distances. However, it is well accepted that some other phenomena, especially those acting at short separation distances, might be relevant and induce substantial changes in the force profiles. Within these phenomena, those related to the surface contact angle, the hydration degree of the ions, or the pH, may dominate the force profiles features, not only at short distances. In this paper, we analyzed the effect of the pH and counterion type on the long-range as well as short-range forces between polystyrene colloidal particles by using the colloidal probe technique based on AFM. Our results confirm that the features of the force profiles between polystyrene surfaces are strongly affected by the pH and hydration degree of the counterions in solution. Additionally, we performed a study of the role of the pH on the wettability properties of hydrated and nonhydrated polystyrene sheets to scan the wettability properties of this material with pH. Contact angle measurements confirmed that the polystyrene surface is hydrophobic in aqueous solutions over the entire range of pHs investigated. These results are in good agreement with the features observed in the force profiles at low pH. At high pH, a short-range repulsion similar to the one observed for hydrophilic materials is observed. This repulsion scales with the pH, and it also depends on the hydration degree of the ions in solution. This way, the short-range forces between polystyrene surfaces may be tunable with the pH, and its origin does not seem to be related to the hydrophobicity of the material.

Numerical study of the most stable contact angle of drops on tilted surfaces.

We present results for the most stable contact angle using a numerical implementation of the tilting plate method of Montes et al. (Montes Ruiz-Cabello, F. J.; Rodriguez-Valverde, M. A.; Cabrerizo-Vilchez, M. Soft Matter 2011, 7, 10457-10461). Comparison with the experimental results is made, obtaining a good agreement in most situations. In addition, the evolution of the contact angles of a tilted drop with a fixed circular line is analyzed. This analysis allows one to theoretically predict the most stable contact angle for tilted drops.

Assessing the impact of As-Cd-Pb metal mixture on cell transformation by two-stage Balb/c 3T3 cell assay.

Human beings are exposed to metals as a consequence of various industrial activities, including glass production, agrochemical production, metallurgy and battery manufacture. New data about the possible mechanisms involved in the carcinogenic activity of these metals are constantly being reported. Exposure to complex mixtures of metals is more likely to occur than exposure to a single metal alone. Among these elements, arsenic, cadmium and lead are ubiquitous air and water pollutants that continue to threaten the quality of public health around the world. The aim of the present study was to evaluate the capability of a mixture of 2 µM NaAsO2, 2 µM CdCl2 and 5 µM Pb(C2H3O2)2·3H2O at relevant epidemiological concentrations to induce cell transformation processes. Transforming potential was determined by a murine two-stage Balb/c 3T3 cell assay. Cell viability, reactive oxygen species (ROS), DNA damage, cell cycle analysis, senescence, generation time and metallothionein expression were also evaluated. The results showed that the metal mixture induced morphological cell transformation only when acting as initiator stimuli of the process. A decrease in cell viability was observed at the promotion stage, a time during which ROS increase, especially when a metal mixture was applied as a promoter stimulant. Changes in DNA damage were not observed throughout the assay; however, we observed G1 cell cycle arrest. The metal mixture, acting as a promoter, is capable of inducing senescence, but metals employed as initiators with 12-O-tetradecanoylphorbol-13-acetate as a promoter are capable of causing avoidance of senescence and triggering the transformation potential of the cells.

Surface activity and collective behaviour of colloidally stable Janus-like particles at the air-water interface.

In this work we report an experimental study on the surface activity and the collective behaviour of colloidally stable Janus-like silver particles at the air-water interface. The colloidal stability of silver nanoparticles has been enhanced using different capping ligands. Two polymers coated the silver particles: 11-mercaptoundecanoic acid and 1-undecanthiol. These capping ligands adsorbed onto the particle surface are spontaneously rearranged at the air-water interface. This feature leads to Janus behaviour in the silver particles with amphiphilic character. The surface activity of the silver particles at the air-water interface has been measured using pendant drop tensiometry. The Janus-like silver particles revealed a surface activity similar to that shown by conventional amphiphilic molecules but with much larger area per particle. The variation of the surface pressure with the area per particle was described properly using the Frumkin isotherm up to the collapse state. Furthermore, oscillating pendant drop tensiometry provided very useful data on the rheological properties of Janus particle monolayers; these properties depended on the lateral interactions between particles and were closely related to the monolayer microstructure. We revealed the close relationship between the collective behavior and the surface activity of Janus-like silver particles.

Evaluation of chemical contamination of crops produced in greenhouse by irrigation with reclaimed water.

Using reclaimed water for agricultural irrigation is increasing worldwide to compensate for water scarcity. The aim of this work was to evaluate the uptake of some of the most commonly detected organic contaminants of emerging concern (CECs) and pesticides in regenerated water in a field study. Furthermore, it was studied their distribution and accumulation in the different parts of a crop (soil, plant and fruit). Three crops (cucumber, pepper and melon) were grown under controlled agronomic conditions in a greenhouse. In order to make an accurate evaluation of the process, "regenerated blank water" was spiked with 70 chemicals (including antibiotics, anti-inflammatories, analgesics, anaesthetics, anxiolytics, anticonvulsants, pesticides) at environmental concentrations (∼1 µg/L) and used for continuous crop irrigation. After crop season, the average total concentration of contaminants detected in the soil samples ranged from 132 to 232 µg/kg d.w depending of the crops type. Between 7 and 10 different contaminants were found in the harvested fruits, up to levels of 27.8 µg/kg f.w. cucumber, 12.4 µg/kg f.w. melon and 7.8 µg/kg f.w pepper. In general, cucumber fruit showed higher accumulation levels of contaminants than pepper and melon for most target analytes. The accumulation rates followed the order: root (0.2 %) < stem/leaf (1-4 %) < fruit (1-6 %) < soil (17-30 %). The experimental data obtained in this study were also used to assess the risk associated with the reuse of reclaimed water for crop irrigation as well to identify those contaminants that, due to their physicochemical properties, show higher accumulation rates and environmental impact.

A dynamic upper atmosphere of Venus as revealed by VIRTIS on Venus Express.

The upper atmosphere of a planet is a transition region in which energy is transferred between the deeper atmosphere and outer space. Molecular emissions from the upper atmosphere (90-120 km altitude) of Venus can be used to investigate the energetics and to trace the circulation of this hitherto little-studied region. Previous spacecraft and ground-based observations of infrared emission from CO2, O2 and NO have established that photochemical and dynamic activity controls the structure of the upper atmosphere of Venus. These data, however, have left unresolved the precise altitude of the emission owing to a lack of data and of an adequate observing geometry. Here we report measurements of day-side CO2 non-local thermodynamic equilibrium emission at 4.3 microm, extending from 90 to 120 km altitude, and of night-side O2 emission extending from 95 to 100 km. The CO2 emission peak occurs at approximately 115 km and varies with solar zenith angle over a range of approximately 10 km. This confirms previous modelling, and permits the beginning of a systematic study of the variability of the emission. The O2 peak emission happens at 96 km +/- 1 km, which is consistent with three-body recombination of oxygen atoms transported from the day side by a global thermospheric sub-solar to anti-solar circulation, as previously predicted.

South-polar features on Venus similar to those near the north pole.

Venus has no seasons, slow rotation and a very massive atmosphere, which is mainly carbon dioxide with clouds primarily of sulphuric acid droplets. Infrared observations by previous missions to Venus revealed a bright 'dipole' feature surrounded by a cold 'collar' at its north pole. The polar dipole is a 'double-eye' feature at the centre of a vast vortex that rotates around the pole, and is possibly associated with rapid downwelling. The polar cold collar is a wide, shallow river of cold air that circulates around the polar vortex. One outstanding question has been whether the global circulation was symmetric, such that a dipole feature existed at the south pole. Here we report observations of Venus' south-polar region, where we have seen clouds with morphology much like those around the north pole, but rotating somewhat faster than the northern dipole. The vortex may extend down to the lower cloud layers that lie at about 50 km height and perhaps deeper. The spectroscopic properties of the clouds around the south pole are compatible with a sulphuric acid composition.

In Vitro Activity of Cefiderocol Compared to Other Antimicrobials against a Collection of Metallo-Beta-Lactamase-Producing Gram-Negative Bacilli from Southern Spain.

In this study, we aimed to comparatively evaluate the in vitro activity of cefiderocol versus other antimicrobials against a well-characterized collection of metallo-beta-lactamase (MBL)-producing Gram-negative bacilli (MBL-GNB) isolates from hospitals in Andalusia, Spain. We recovered 232 MBL-GNB from Andalusian hospitals, including 160 Enterobacterales and 72 nonfermenting Gram-negative bacilli belonging to 44 different clones (2015 to 2020). Cefiderocol and comparator MICs were determined with commercial methods (UMIC [Bruker] and EUMDROXF [Sensititre; Thermo Fisher], respectively). EUCAST breakpoints were used for all antimicrobials tested, and CLSI also was used for cefiderocol. Control strains used were E. coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. Cefiderocol showed potent in vitro activity against isolates tested, regardless of breakpoint (susceptibility rates, 85.3% for EUCAST versus 96.6% for CLSI, P < 0.001). MIC ranges for Enterobacterales and nonfermenting Gram-negative bacilli (NF-GNB) were ≤0.03 to 1 mg/L and 0.06 to 2 (IMP), 0.06 to 8 mg/L and 0.06 to 16 (VIM), 0.25 to 16 mg/L and 2 to 16 mg/L (NDM), respectively, and 0.25 to 8 mg/L for double MBL-producing Enterobacterales. By species, all cefiderocol-susceptible rates were over 90%, except Klebsiella oxytoca, Enterobacter cloacae, Escherichia coli, and Acinetobacter spp. Significant differences were observed comparing resistant isolates between Enterobacterales and NF-GNB by EUCAST (19.4% versus 4.2%, P < 0.01), but not by CLSI (4.4% versus 1.4%, P = 0.2). Cefiderocol was the most active antimicrobial tested. Cefiderocol showed excellent in vitro activity against MBL-GNB, especially NF-GNB; almost all isolates resistant to comparators were susceptible. IMPORTANCE This article demonstrates the efficacy of cefiderocol against a large collection of well-characterized metallo-beta-lactamase-producing isolates, some of them even producing double carbapenemases. Furthermore, cefiderocol activity is compared to other novel broad-spectrum antimicrobials with activity against carbapenemases.

Long-term effects on the agroecosystem of using reclaimed water on commercial crops.

The use of reclaimed water for crop irrigation has been proposed as a suitable alternative for farmers in the coastal areas of Mediterranean countries, which suffer from greater water scarcity. In this work we study the impact on the water-soil-plant continuum of using reclaimed water for commercial crops irrigated over a long period, as well as the human risks associated with consuming the vegetables produced. Forty-four CECs were identified in the reclaimed water used for crop irrigation. Of these, twenty-four CECs were identified in the irrigated soil samples analysed. Tramadol, ofloxacin, tonalide, gemfibrozil, atenolol, caffeine, and cetirizine were the pharmaceuticals detected at the highest levels in the water samples (between 11 and 44 µg/L). The CECs with the highest average soil concentrations were tramadol (14.6 µg/kg), followed by cetirizine (13.2 µg/kg) and clarithromycin (12.7 µg/kg). In the irrigated vegetable samples analysed over the study period, carbamazepine, lidocaine, and caffeine were only detected at levels from 0.1 to 1.7 µg/kg. The CEC accumulation rate detected in the edible parts of the vegetables permanently irrigated with reclaimed water was very low (~1 %), whereas it was 33 % in the soils. The results revealed that consuming fruits harvested from plants irrigated for a long period with reclaimed water does not represent a risk to human health, opening the door to a circular economy of water. Nevertheless, for crop irrigation, future studies need to be conducted over longer periods and in other matrices to provide more scientific data on the safety of using reclaimed water.

Fate, modeling, and human health risk of organic contaminants present in tomato plants irrigated with reclaimed water under real-world field conditions.

Using reclaimed water to irrigate crops can be an important route for organic contaminants of emerging concern (CECs) to be introduced into agricultural production and thus find their way into the food chain. This work aims to establish accumulation models for the different parts of a crop (fruit/leaves/roots) and the soil of some of the most commonly detected CECs in reclaimed water, through field trials in greenhouses. For this, tomato plants were permanently irrigated under realistic agricultural conditions with a mixture of the selected compounds at approx. 1 µg/L. A total of 30 contaminants were analyzed belonging to different compound categories. A modified QuEChERS extraction method followed by liquid chromatography coupled to tandem mass spectrometry was the procedure used. The study revealed the presence of 21 target contaminants in the tomatoes, and 18 CECs in the leaves, roots, and soil. The average total concentration of pesticides detected in the tomatoes was 3 µg/kg f.w., whereas the average total load of pharmaceuticals was 5.8 µg/kg f.w. after three months, at the time of crop harvesting. The levels of pharmaceutical products and pesticides in the non-edible tissues were up to 3.5 and 2.1 µg/kg f.w., respectively, in the leaves and up to 89.3 and 31.3 µg/kg f.w., respectively, in the roots. In the case of the soil samples, the pesticide concentration found after crop harvesting was below 11.4 µg/kg d.w., and less than 3.0 µg/kg d.w. for pharmaceuticals. Overall, the concentration levels of CECs detected in the tomatoes, which were permanently irrigated with contaminated reclaimed water, do not pose a risk to human health via dietary intake.

Co-axial printing of convoluted proximal tubule for kidney disease modeling.

Despite the increasing incidence of kidney-related diseases, we are still far from understanding the underlying mechanisms of these diseases and their progression. This lack of understanding is partly because of a poor replication of the diseasesin vitro,limited to planar culture. Advancing towards three-dimensional models, hereby we propose coaxial printing to obtain microfibers containing a helical hollow microchannel. These recapitulate the architecture of the proximal tubule (PT), an important nephron segment often affected in kidney disorders. A stable gelatin/alginate-based ink was formulated to allow printability while maintaining structural properties. Fine-tuning of the composition, printing temperature and extrusion rate allowed for optimal ink viscosity that led to coiling of the microfiber's inner channel. The printed microfibers exhibited prolonged structural stability (42 days) and cytocompatibility in culture. Healthy conditionally immortalized PT epithelial cells and a knockout cell model for cystinosis (CTNS-/-) were seeded to mimic two genotypes of PT. Upon culturing for 14 days, engineered PT showed homogenous cytoskeleton organization as indicated by staining for filamentous actin, barrier-formation and polarization with apical markerα-tubulin and basolateral marker Na+/K+-ATPase. Cell viability was slightly decreased upon prolonged culturing for 14 days, which was more pronounced inCTNS-/-microfibers. Finally,CTNS-/-cells showed reduced apical transport activity in the microfibers compared to healthy PT epithelial cells when looking at breast cancer resistance protein and multidrug resistance-associated protein 4. Engineered PT incorporated in a custom-designed microfluidic chip allowed to assess leak-tightness of the epithelium, which appeared less tight inCTNS-/-PT compared to healthy PT, in agreement with itsin vivophenotype. While we are still on the verge of patient-oriented medicine, this system holds great promise for further research in establishing advancedin vitrodisease models.

Global Vertical Distribution of Water Vapor on Mars: Results From 3.5 Years of ExoMars-TGO/NOMAD Science Operations.

We present water vapor vertical distributions on Mars retrieved from 3.5 years of solar occultation measurements by Nadir and Occultation for Mars Discovery onboard the ExoMars Trace Gas Orbiter, which reveal a strong contrast between aphelion and perihelion water climates. In equinox periods, most of water vapor is confined into the low-middle latitudes. In aphelion periods, water vapor sublimated from the northern polar cap is confined into very low altitudes-water vapor mixing ratios observed at the 0-5 km lower boundary of measurement decrease by an order of magnitude at the approximate altitudes of 15 and 30 km for the latitudes higher than 50°N and 30-50°N, respectively. The vertical confinement of water vapor at northern middle latitudes around aphelion is more pronounced in the morning terminators than evening, perhaps controlled by the diurnal cycle of cloud formation. Water vapor is also observed over the low latitude regions in the aphelion southern hemisphere (0-30°S) mostly below 10-20 km, which suggests north-south transport of water still occurs. In perihelion periods, water vapor sublimated from the southern polar cap directly reaches high altitudes (>80 km) over high southern latitudes, suggesting more effective transport by the meridional circulation without condensation. We show that heating during perihelion, sporadic global dust storms, and regional dust storms occurring annually around 330° of solar longitude (L S) are the main events to supply water vapor to the upper atmosphere above 70 km.

Population pharmacokinetic/pharmacogenetic model for optimization of efavirenz therapy in Caucasian HIV-infected patients.

Despite extensive clinical experience with efavirenz (EFV), unpredictable interindividual variabilities in efficacy and toxicity remain important limitations associated with the use of this antiretroviral. The purpose of this study was to determine the factors affecting EFV pharmacokinetics and to develop a pharmacokinetic/pharmacogenetic (PK/PG) model in a Caucasian population of HIV-infected patients. In total, 869 EFV plasma concentrations from 128 HIV-infected patients treated with EFV were quantitatively assessed using a validated high-performance liquid chromatography technique. All patients were genotyped for 90 single nucleotide polymorphisms (SNPs) in genes coding for proteins involved in the metabolism and transport of EFV, using a MassArray platform provided by Sequenom. The influence of these polymorphisms on EFV pharmacokinetics and the effects of demographic, clinical, biochemical, lifestyle, and concurrent drug covariates were evaluated. Plasma concentrations were fitted by a one-compartment model, with first-order absorption and elimination using nonlinear mixed-effect modeling (NONMEM program). The CYP2B6*6 allele, multidrug resistance-associated protein 4 (MRP4) 1497C → T, and gamma-glutamyltranspeptidase (GGT) were identified as major factors influencing the apparent EFV oral clearance (CL/F), reducing the initial interindividual variability by 54.8%, according to the model CL/F = (12.2 - 0.00279 · GGT) · 0.602(CYP2B6*6 [G/T]) · 0.354(CYP2B6*6 [T/T]) · 0.793(MRP4 1497C → T), where CYP2B6*6 [G/T], CYP2B6*6 [T/T], and MRP4 1497C → T take values of 0 or 1 to indicate the absence or presence of polymorphisms. The detailed genetic analysis conducted in this study identified two of 90 SNPs that significantly impacted CL/F, which might indicate that the remaining SNPs analyzed do not influence this PK parameter, at least in Caucasian populations with characteristics similar to those of our study population.