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A new container-less droplet merging method in combination with high-speed imaging and spectroscopy were employed to explore the chemistry in the initial stages of ignition in a hyperogolic ionic liquid – oxidizer reaction.

In the past decade it has become evident that neuroblasts continue to supply the human cortex with interneurons via unique migratory streams shortly following birth. Owing to the size of the human brain, these newborn neurons must migrate long distances through complex cellular landscapes to reach their final locations. This process is poorly understood, largely because of technical difficulties in acquiring and studying neurotypical postmortem human samples along with diverging developmental features of well-studied mouse models. We reasoned that migratory streams of neuroblasts utilize cellular substrates, such as blood vessels, to guide their trek from the subventricular zone to distant cortical targets. Here, we evaluate the association between young interneuronal migratory streams and their preferred cellular substrates in gyrencephalic piglets during the developmental equivalent of human birth, infancy, and toddlerhood. US National Institutes of Health [R15NS108183] Published version ACKNOWLEDGMENTS We gratefully thank Drs. Sherrie Clark-Deener and Calvin Lau for their assistance with veterinary services. We are also thankful to Jessica Neary and Garrett Walker for assistance in animal husband-ry. We also would like to thank Raymundo Hernandez, Beatriz Torres, Swagatika Paul, and Dr. Alicia Pickrell for technical advice. We would like to acknowledge Karen Hall and Rachel McNeil for animal care. This work was supported by the US National Institutes of Health (R15NS108183 to P.D.M.) .

Iron is an essential nutrient that regulates productivity in ~30% of the ocean. Compared with deep (>2000 meter) hydrothermal activity at mid-ocean ridges that provide iron to the ocean’s interior, shallow (2 .

A survey, developed with the Theory of Planned Behavior, was used to assess school administrators’ intention to promote adapted physical education (APE). Survey results indicated that when school administrators’ attitudes and subjective norms were favorable, the intention to promote APE was subsequently higher. The results indicate that if we expect public school administrators to promote APE in schools, they must know the importance of high-quality physical education to students with disabilities.

We present a multiwavelength investigation of the H ii region G347.600+00.211, located at a distance of 7.9 kpc. We analyse the gas and dust properties aiming to disentangle the origin of the region as well as its role in the formation of new stars. G347.600 + 00.211 is very conspicuous at 1420 MHz and infrared wavelengths, showing an incomplete shell-like structure with two distinct zones of very intense emission. The infrared bubble S8 is part of the shell structure. The spatial distribution of the molecular gas shows the presence of six clouds located around the ionized region and showing a good morphological correlation with the 8-$\mu$m emission. Cold dust is coincident with the dense gas shown in the CO measurements. As for the origin of the region, we found that the massive cluster [DBS2003]179 and two Wolf–Rayet (WR) stars are located at the same distance than the ionized gas. Based on a stellar density analysis, we inferred that one of the WR stars, 1181-81L, is also a probable member of the cluster. Both the cluster and the WR stars are not only within the ring-like structure, but are also located near the two spots of very heightened emission, suggesting they may be responsible for this bright emission. Finally, as expanding H ii regions are hypothesized to trigger star formation, we used different infrared point source catalogues to search for young stellar object candidates (cYSOs). A total of 33 cYSOs and 4 CH ii regions were identified projected on to the photodissociation regions and molecular clouds.

The chemical composition of gases emitted by active volcanoes reflects both magma degassing and shallower processes, such as fluid-rock hydrothermal interaction and mixing with atmospheric-derived fluids. Untangling the magmatic fluid endmember within surface gas emission is therefore challenging, even with the use of well-known magma degassing tracers such as noble gases. Here, we investigate the deep magmatic fluid composition at the Nisyros caldera (Aegean Arc, Greece) by measuring nitrogen and noble gas abundances and isotopes in naturally degassing fumaroles. Gas samples were collected from 32 fumarolic vents at water-boiling temperature between 2018 and 2021. These fumaroles are admixtures of magmatic fluids typical of subduction zones, groundwater (or air saturated water, ASW), and air. The N2, He, and Ar composition of the magmatic endmember is calculated by reverse mixing modeling and shows N2/He = 31.8 ± 4.5, N2/Ar = 281.6, δ15N = +7 ± 3 ‰, 3He/4He = 6.2 Ra (where Ra is air 3He/4He), and 40Ar/36Ar = 551.6 ± 19.8. Although N2/He is significantly low with respect to typical values for arc volcanoes (1,000–10,000), the contribution of subducted sediments to the Aegean Arc magma generation is reflected by the positive δ15N values of Nisyros fumaroles. The low N2/He ratio indicates N2-depletion due to solubility-controlled differential degassing of an upper-crustal silicic (dacitic/rhyodacitic) melt in a high-crystallinity reservoir. We compare our 2018–2021 data with N2, He, and Ar values collected from the same fumaroles during a hydrothermal unrest following the seismic crisis in 1996–1997. Results show additions of both magmatic fluid and ASW during this unrest. In the same period, fumarolic vents display an increase in magmatic species relative to hydrothermal gas, such as CO2/CH4 and He/CH4 ratios, an increase of ∼50 °C in the equilibrium temperature of the hydrothermal system (up to 325 °C), and greater amounts of vapor separation. These variations reflect an episode of magmatic fluid expulsion during the seismic crisis. The excess of heat and mass supplied by the magmatic fluid injection is then dissipated through boiling of deeper and peripheral parts of the hydrothermal system. Reverse mixing modeling of fumarolic N2-He-Ar has therefore important ramifications not only to disentangle the magmatic signature from gases emitted during periods of dormancy, but also to trace episodes of magmatic outgassing and better understand the state of the upper crustal reservoir., Geochimica et Cosmochimica Acta, 335, ISSN:0016-7037, ISSN:1872-9533

Background Despite having a high healthcare need, persons with complex conditions are less likely to receive comprehensive care. Individuals with SCI experience difficulties accessing services 2-4 times more than the general population. There is little agreement concerning the factors that influence these access restrictions. Few studies focus on health system impact on characteristics on access. Objective To outline barriers and facilitators to service access among persons with SCI across 22 countries in terms of health system characteristics Methods InSCI(2017): 1st community survey on experience of persons with SCI, 12591 participants, 22 countries (Australia, Brazil, China, France, Germany, Greece, Indonesia, Italy, Japan, Lithuania, Malaysia, Morocco, the Netherlands, Norway, Poland, Romania, South Africa, South Korea, Spain, Switzerland, Thailand, USA). Data analysis 1. Hierarchical cluster analysis based on Gower distance (to group systems by access restrictions: Acceptability, Approachability, Availability, Affordability, Appropriateness). 2. Generalized linear mixed-effects decision tree (to explore the association of system characteristics and access, including WHO and OECD system indicators (e.g. UHC index, expenditure, human resources). Missing values were imputed with missforest. Results 12% of persons with SCI reported having an access restriction, most of them (7%) with Availability. By country, the highest unmet needs were reported in Poland (25%), Germany, Lithuania, and Romania (13). 1. Cluster analysis: 7 health systems clusters (groups) were identified. 2. By June 2022, we will have the results of the second analysis: the association of system characteristics with access and how it is modified by socio-demographic and medical factors. Expected conclusions The study identifies factors a country could modify in order to improve access and strengthen the system for persons with SCI/disability, that might be relevant to general population as well. Key messages • Persons with SCI often experience similar access restrictions across countries, incl. those with high-performing health systems. System strengthening in this area is further required in all countries. • Health systems are fragmented, e.g. healthcare quality and access inside a country differs by region, urban/rural setting etc., hence, the systems are challenging to classify.

Post-orogenic back-arc magmatism is accompanied by hydrothermal ore deposits and mineralizations derived from mantle and crustal sources. We investigate Zannone Island (ZI), back-arc Tyrrhenian basin, Italy, to define the source(s) of mineralizing hydrothermal fluids and their relationships with the regional petrological-tectonic setting. On ZI, early Miocene thrusting was overprinted by late Miocene post-orogenic extension and related hydrothermal alteration. Since active submarine hydrothermal outflow is reported close to the island, Zannone provides an ideal site to determine the P-T-X evolution of the long-lived hydrothermal system. We combined field work with microstructural analyses on syn-tectonic quartz veins and carbonate mineralizations, X-ray diffraction analysis, microthermometry and element mapping of fluid inclusions (FIs), C, O, and clumped isotopes, and analyses of noble gases (He-Ne-Ar) and CO2 content in FIs. Our results document the evolution of a fluid system of magmatic origin with increasing mixing of meteoric fluids. Magmatic fluids were responsible for quartz veins precipitation at similar to 125 to 150 MPa and similar to 300 degrees C-350 degrees C. With the onset of extensional faulting, magmatic fluids progressively interacted with carbonate rocks and mixed with meteoric fluids, leading to (a) host rock alteration with associated carbonate and minor ore mineral precipitation, (b) progressive fluid neutralization, (c) cooling of the hydrothermal system (from similar to 320 degrees C to similar to 86 degrees C), and (d) embrittlement and fracturing of the host rocks. Both quartz and carbonate mineralizations show noble gases values lower than those from the adjacent active volcanic areas and submarine hydrothermal systems, indicating that the fossil-to-active hydrothermal history is associated with the emplacement of multiple magmatic intrusions., Geochemistry, Geophysics, Geosystems, 23 (10), ISSN:1525-2027

A major barrier to adeno-associated virus (AAV) gene therapy is the inability to re-dose patients due to formation of vector-induced neutralizing antibodies (Nabs). Tolerogenic nanoparticles encapsulating rapamycin (ImmTOR) provide long-term and specific suppression of adaptive immune responses, allowing for vector re-dosing. Moreover, co-administration of hepatotropic AAV vectors and ImmTOR leads to an increase of transgene expression even after the first dose. ImmTOR and AAV Anc80 encoding the methylmalonyl-coenzyme A (CoA) mutase (MMUT) combination was tested in a mouse model of methylmalonic acidemia, a disease caused by mutations in the MMUT gene. Repeated co-administration of Anc80 and ImmTOR was well tolerated and led to nearly complete inhibition of immunoglobulin (Ig)G antibodies to the Anc80 capsid. A more profound decrease of plasma levels of the key toxic metabolite, plasma methylmalonic acid (pMMA), and disease biomarker, fibroblast growth factor 21 (FGF21), was observed after treatment with the ImmTOR and Anc80-MMUT combination. In addition, there were higher numbers of viral genomes per cell (vg/cell) and increased transgene expression when ImmTOR was co-administered with Anc80-MMUT. These effects were dose-dependent, with the higher doses of ImmTOR providing higher vg/cell and mRNA levels, and an improved biomarker response. Combining of ImmTOR and AAV can not only block the IgG response against capsid, but it also appears to potentiate transduction and enhance therapeutic transgene expression in the mouse model., Graphical abstract, Kishimoto and colleagues extend their earlier findings showing that combining ImmTOR rapamycin-encapsulated nanoparticles with hepatotropic AAV vector leads to increased transduction, transgene expression, and suppression of IgG responses and therefore enables effective therapeutic AAV vector re-dosing in a mouse model of methylmalonic acidemia, an inborn metabolic disease.

The energy test of multivariate normality is an affine invariant test based on a characterization of equal distributions by energy distance. The test statistic is a degenerate kernel V-statistic, which asymptotically has a sampling distribution that is a Gaussian quadratic form under the null hypothesis of normality. The parameters of the limit distribution are the eigenvalues of the integral operator determined by the energy distance. Although a Monte Carlo approach provides excellent approximations to the sampling distribution of the test statistic for finite samples, in this work we develop two methods to obtain the eigenvalues and the asymptotic distribution of the energy test statistic. We derive the explicit integral equations for the eigenvalue problem for the simple and composite hypotheses of normality and solve them by a variation of Nystrom’s method. For the simple hypothesis, we also obtain the eigenvalues by an empirical approach which we call the sample kernel method. Numerical results are summarized in tables of derived eigenvalues for several cases. The resulting probability distribution in each case is obtained by Imhof’s method. We also include simulation results that illustrate that for large samples the derived limit distribution is quite accurate in the upper tail. Software is available in the energy package for R to implement the tests by the original (Monte Carlo) approach and by applying the new methods using the derived asymptotic distribution.

The term self-regulation (SR) refers to a set of specific cognitive skills necessary for students to independently manage, monitor, and assess their own academic learning and behavior. Students with and at risk for emotional and behavioral disorders (EBD) often lack these skills. This article provides educators with step-by-step procedures and information on three research- or evidence-based SR strategies they can implement in their classrooms: self-regulated strategy development, self-monitoring, and strategy instruction.

Since their approval in 2011, immune checkpoint inhibitors (ICPis) are increasingly used to treat several advanced cancers. ICPis target certain cellular molecules that regulate immune response resulting in antitumor activity. The use of these new agents needs careful monitoring since they brought a whole new spectrum of adverse events. In this review, we aim to describe different endocrine dysfunctions induced by ICPis and to underline the importance of diagnosing and managing these adverse effects. Immune-related endocrine toxicities include thyroid dysfunction, hypophysitis and, less frequently, type 1 diabetes, primary adrenal insufficiency and hypoparathyroidism. Diagnosis of endocrine adverse events related to ICPis therapy can be challenging due to nonspecific manifestations in an oncological scenario and difficulties in the biochemical evaluation. Despite the fact that these endocrine adverse events could lead to life-threatening consequences, the availability of effective replacement treatment enables continuing therapy and together with an interdisciplinary approach will impact positively on survival.

After a stressful event, adaptative mechanisms are carried out to support vital functions. Hypothalamic-pituitary-adrenal axis plays a key role in stress response regulating metabolism, cardiovascular function and immune system. This review addresses pathophysiological changes of the adrenal axis during critical illness, recognizing limitations of methods applied for its evaluation in this special context and defining indications for corticosteroid replacement in critically ill patients. The concept of relative adrenal insufficiency should be abandoned; cosyntropin stimulation test should not be performed for diagnosis of adrenal insufficiency in critical illness nor for establishing the need of treatment.Diversos mecanismos adaptativos se ponen en marcha para sostener las funciones orgánicas vitales en el paciente crítico. El eje hipotálamo-hipófiso-adrenal tiene un papel clave en la respuesta al estrés al regular el metabolismo, la función cardiovascular y la respuesta inmune. Esta revisión tiene por objetivos analizar los cambios fisiopatológicos que se producen en el eje adrenal durante la enfermedad crítica, reconocer las limitaciones de los métodos diagnósticos y definir indicaciones de tratamiento de reemplazo corticoideo en este contexto. El concepto de insuficiencia adrenal relativa debe ser descartado y no se recomienda el test de estímulo con cosintropina para diagnóstico de insuficiencia adrenal durante enfermedad crítica ni para definir la necesidad de tratamiento.

Constraining the magmatic 3He/4He signature of fluids degassed from a magmatic system is crucial for making inferences on its mantle source. This is especially important in arc volcanism, where variations in the composition of the wedge potentially induced by slab sediment fluids must be distinguished from the effects of magma differentiation, degassing, and crustal contamination. The study of fluid inclusions (FIs) trapped in minerals of volcanic rocks is becoming an increasingly used methodology in geochemical studies that integrates the classical study of volcanic and geothermal fluids. Here, we report on the first noble gas (He, Ne, Ar) concentrations and isotopic ratios of FI in olivine (Ol) and pyroxene (Px) crystals separated from eruptive products of the Telica and Baru volcanoes, belonging to the Nicaraguan and Panamanian arc-segments of Central America Volcanic arc (CAVA). FIs from Telica yield air corrected 3He/4He (Rc/Ra) of 7.2–7.4 Ra in Ol and 6.1–7.3 in Px, while those from Baru give 7.1–8.0 Ra in Ol and 4.2–5.8 Ra in Px. After a data quality check and a comparison with previous 3He/4He measurements carried out on the same volcanoes and along CAVA, we constrained a magmatic Rc/Ra signature of 7.5 Ra for Telica and of 8.0 Ra for Baru, both within the MORB range (8 ± 1 Ra). These 3He/4He differences also reflect variations in the respective arc-segments, which cannot be explained by radiogenic 4He addition due to variable crust thickness, as the mantle beneath Nicaragua and Panama is at about 35 and 30 km, respectively. We instead highlight that the lowest 3He/4He signature observed in the Nicaraguan arc segment reflects a contamination of the underlying wedge by slab sediment fluids. Rc/Ra values up to 9.0 Ra are found at Pacaya volcano in Guatemala, where the crust is 45 km thick, while a 3He/4He signature of about 8.0 Ra was measured at Turrialba volcano in Costa Rica, which is similar to that of Baru, and reflects possible influence of slab melting, triggered by a change in subduction conditions and the contemporary subduction of the Galapagos hot-spot track below southern Costa Rica and western Panama.