Voriconazole is safe and effective as prophylaxis for early and late fungal infections following allogeneic hematopoietic stem cell transplantation

Seventy-two patients undergoing allogeneic transplantation were treated with voriconazole (VOR) as antifungal prophylaxis starting from day −2 of transplantation and continuing until withdrawal of immunosuppression. Patients were assessed for safety and the incidence of definite, probable, or possible fungal infection throughout transplantation was evaluated. VOR was well tolerated. Only 14% of patients required interruption of VOR therapy because of toxicity: liver toxicity (8%), cardiac Q –T interval prolongation (1%), or other side effects (5%). In the early post-transplant period (120 days), no patients developed probable or definite fungal infection while receiving VOR. No Candida infections were seen in either period. These data suggest that fungal prophylaxis with VOR following allogeneic transplantation is safe and effective.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73360/1/j.1399-3062.2009.00455.x.pd

Projections of Atmospheric Nitrogen Deposition to the Chesapeake Bay Watershed

Atmospheric deposition is among the largest pathways of nitrogen loading to the Chesapeake Bay Watershed (CBW). The interplay between future climate and emission changes in and around the CBW will likely shift the future nutrient deposition abundance and chemical regime (e.g., oxidized vs. reduced nitrogen). In this work, a Representative Concentration Pathway from the Community Earth System Model is dynamically downscaled using a recently updated Weather Research and Forecasting model that subsequently drives the Community Multiscale Air Quality model coupled to the agroeconomic Environmental Policy Integrated Climate model. The relative impacts of emission and climate changes on atmospheric nutrient deposition are explored for a recent historical period and a period centered on 2050. The projected regional emissions in Community Multiscale Air Quality reflect current federal and state regulations, which use baseline and projected emission years 2011 and 2040, respectively. The historical simulations of 2-m temperature (T2) and precipitation (PRECIP) have cool and dry biases, and temperature and PRECIP are projected to both increase. Ammonium wet deposition agrees well with observations, but nitrate wet deposition is underpredicted. Climate and deposition changes increase simulated future ammonium fertilizer application. In the CBW by 2050, these changes (along with widespread decreases in anthropogenic nitrogen oxide and sulfur oxide emissions, and relatively constant ammonia emissions) decrease total nitrogen deposition by 21%, decrease annual average oxidized nitrogen deposition by 44%, and increase reduced nitrogen deposition by 10%. These results emphasize the importance of decreased anthropogenic emissions on the control of future nitrogen loading to the Chesapeake Bay in a changing climate

Leader Cells Define Directionality of Trunk, but Not Cranial, Neural Crest Cell Migration.

Collective cell migration is fundamental for life and a hallmark of cancer. Neural crest (NC) cells migrate collectively, but the mechanisms governing this process remain controversial. Previous analyses in Xenopus indicate that cranial NC (CNC) cells are a homogeneous population relying on cell-cell interactions for directional migration, while chick embryo analyses suggest a heterogeneous population with leader cells instructing directionality. Our data in chick and zebrafish embryos show that CNC cells do not require leader cells for migration and all cells present similar migratory capacities. In contrast, laser ablation of trunk NC (TNC) cells shows that leader cells direct movement and cell-cell contacts are required for migration. Moreover, leader and follower identities are acquired before the initiation of migration and remain fixed thereafter. Thus, two distinct mechanisms establish the directionality of CNC cells and TNC cells. This implies the existence of multiple molecular mechanisms for collective cell migration.D11I1096 Fondo de Fomento al Desarrollo Científico y TecnológicoThis is the final version of the article. It first appeared from Cell Press via httsp://doi.org/10.1016/j.celrep.2016.04.06

Synthesis of 3-D coronal-solar wind energetic particle acceleration modules

1. Introduction Acute space radiation hazards pose one of the most serious risks to future human and robotic exploration. Large solar energetic particle (SEP) events are dangerous to astronauts and equipment. The ability to predict when and where large SEPs will occur is necessary in order to mitigate their hazards. The Coronal-Solar Wind Energetic Particle Acceleration (C-SWEPA) modeling effort in the NASA/NSF Space Weather Modeling Collaborative [Schunk, 2014] combines two successful Living With a Star (LWS) (http://lws. gsfc.nasa.gov/) strategic capabilities: the Earth-Moon-Mars Radiation Environment Modules (EMMREM) [Schwadron et al., 2010] that describe energetic particles and their effects, with the Next Generation Model for the Corona and Solar Wind developed by the Predictive Science, Inc. (PSI) group. The goal of the C-SWEPA effort is to develop a coupled model that describes the conditions of the corona, solar wind, coronal mass ejections (CMEs) and associated shocks, particle acceleration, and propagation via physics-based modules. Assessing the threat of SEPs is a difficult problem. The largest SEPs typically arise in conjunction with X class flares and very fast (\u3e1000 km/s) CMEs. These events are usually associated with complex sunspot groups (also known as active regions) that harbor strong, stressed magnetic fields. Highly energetic protons generated in these events travel near the speed of light and can arrive at Earth minutes after the eruptive event. The generation of these particles is, in turn, believed to be primarily associated with the shock wave formed very low in the corona by the passage of the CME (injection of particles from the flare site may also play a role). Whether these particles actually reach Earth (or any other point) depends on their transport in the interplanetary magnetic field and their magnetic connection to the shock

Ab initio calculations of the physical properties of transition metal carbides and nitrides and possible routes to high-Tc

Ab initio linear-response calculations are reported of the phonon spectra and the electron-phonon interaction for several transition metal carbides and nitrides in a NaCl-type structure. For NbC, the kinetic, optical, and superconducting properties are calculated in detail at various pressures and the normal-pressure results are found to well agree with the experiment. Factors accounting for the relatively low critical temperatures Tc in transition metal compounds with light elements are considered and the possible ways of increasing Tc are discussed.Comment: 19 pages, 7 figure

The first widespread solar energetic particle event of solar cycle 25 on 2020 November 29 : Shock wave properties and the wide distribution of solar energetic particles

Context. On 2020 November 29, an eruptive event occurred in an active region located behind the eastern solar limb as seen from Earth. The event consisted of an M4.4 class flare, a coronal mass ejection, an extreme ultraviolet (EUV) wave, and a white-light (WL) shock wave. The eruption gave rise to the first widespread solar energetic particle (SEP) event of solar cycle 25, which was observed at four widely separated heliospheric locations (similar to 230 degrees). Aims. Our aim is to better understand the source of this widespread SEP event, examine the role of the coronal shock wave in the wide distribution of SEPs, and investigate the shock wave properties at the field lines magnetically connected to the spacecraft. Methods. Using EUV and WL data, we reconstructed the global three-dimensional structure of the shock in the corona and computed its kinematics. We determined the magnetic field configurations in the corona and interplanetary space, inferred the magnetic connectivity of the spacecraft with the shock surface, and derived the evolution of the shock parameters at the connecting field lines. Results. Remote sensing observations show formation of the coronal shock wave occurring early during the eruption, and its rapid propagation to distant locations. The results of the shock wave modelling show multiple regions where a strong shock has formed and efficient particle acceleration is expected to take place. The pressure/shock wave is magnetically connected to all spacecraft locations before or during the estimated SEP release times. The release of the observed near-relativistic electrons occurs predominantly close to the time when the pressure/shock wave connects to the magnetic field lines or when the shock wave becomes supercritical, whereas the proton release is significantly delayed with respect to the time when the shock wave becomes supercritical, with the only exception being the proton release at the Parker Solar Probe. Conclusions. Our results suggest that the shock wave plays an important role in the spread of SEPs. Supercritical shock regions are connected to most of the spacecraft. The particle increase at Earth, which is barely connected to the wave, also suggests that the cross-field transport cannot be ignored. The release of energetic electrons seems to occur close to the time when the shock wave connects to, or becomes supercritical at, the field lines connecting to the spacecraft. Energetic protons are released with a time-delay relative to the time when the pressure/shock wave connects to the spacecraft locations. We attribute this delay to the time that it takes for the shock wave to accelerate protons efficiently.Peer reviewe

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis