All You Need to Know and More about the Diagnosis and Management of Rare Mold Infections

Invasive mold infections caused by molds other than Aspergillus spp. or Mucorales are emerging. The reported prevalences of infection due to these rare fungal pathogens vary among geographic regions, driven by differences in climatic conditions, susceptible hosts, and diagnostic capabilities. These rare molds-Fusarium, Lomentospora, and Scedosporium species and others-are difficult to detect and often show intrinsic antifungal resistance. Now, international societies of medical mycology and microbiology have joined forces and created the Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology (published in Lancet Infect Dis, https://doi.org/10.1016/S1473-3099(20)30784-2), with the goal of improving the diagnosis, treatment, prevention, and survival of persons with rare mold infections. The guideline provides cutting-edge guidance for the correct utilization and application of established and new diagnostic and therapeutic options

Chemical Engineering Division waste management programs. Quarterly report, April--June 1975

Consolidation techniques for Zircaloy fuel-cladding hulls were studied. They included (1) further work on a pyrochemical-volatility scheme for separating the zirconium as the volatile tetrachloride and (2) ignition tests and shock- ignition tests on several Zircaloy materials to further characterize the pyrophoric behavior of Zircaloy and the impact on hulls management. Quantitative results on the reaction with molten zinc chloride are presented. A series of steel-melting experiments examined the compatibility of various crucible materials with the molten steel and provided information on the behavior (distribution) of CeO$sub 2$ and UO$sub 2$ (used as stand-ins for PuO$sub 2$). Examination of existing information on deep-well injection of industrial wastes and on low-level aqueous wastes from fuel reprocessing led to the conclusions that the technology is generally available from industrial practice, that costs are of the order of 10$sup -4$ mill/kWh, that environmental effects could be insignificant in normal operation (but could include contamination of groundwater and resources and also stimulation of minor earthquakes in maloperation), that legal constraints may be the most significant barrier to adopting the practice, and that the site of such an operation would best be at a fuel reprocessing plant located at one of the U. S. sedimentary basins. The conclusions and recommendations from a study of the reliability of high-level-waste canisters are presented. (auth

Chord distribution functions of three-dimensional random media: Approximate first-passage times of Gaussian processes

The main result of this paper is a semi-analytic approximation for the chord distribution functions of three-dimensional models of microstructure derived from Gaussian random fields. In the simplest case the chord functions are equivalent to a standard first-passage time problem, i.e., the probability density governing the time taken by a Gaussian random process to first exceed a threshold. We obtain an approximation based on the assumption that successive chords are independent. The result is a generalization of the independent interval approximation recently used to determine the exponent of persistence time decay in coarsening. The approximation is easily extended to more general models based on the intersection and union sets of models generated from the iso-surfaces of random fields. The chord distribution functions play an important role in the characterization of random composite and porous materials. Our results are compared with experimental data obtained from a three-dimensional image of a porous Fontainebleau sandstone and a two-dimensional image of a tungsten-silver composite alloy.Comment: 12 pages, 11 figures. Submitted to Phys. Rev.

Chemical Engineering Division waste management programs. Quarterly report, January--March 1975

Development work on the study of consolidation techniques for Zircaloy fuel-cladding hulls included scouting tests on volatility schemes for separating the zirconium as the volatile tetrachloride and ignition tests on several Zircaloy materials to further characterize the pyrophoric behavior of Zircaloy. All tests were with nonirradiated metal pending acquisition of irradiated samples. Installation is nearly complete of a glovebox facility for studies on the salvage of alpha-contaminated metals by pyrochemical methods. Disposal of a major portion of fission product tritium formed in light water reactor fuels by deep- well injection of the low-level aqueous waste from plants reprocessing such fuels is being evaluated. The question of siting is a very important factor in determining the feasibility of this particular disposal option. A review is given of the status of information for U. S. sedimentary basins, the areas most likely to be generally suitable for siting of waste wells. Work on the reliability of high-level-waste canisters included an examination of creep, shot- peening, and subcooling of the filler canister below storage temperatures, as methods of relieving stresses induced in canisters due to differential contraction of canister and glass during cooling. A method was investigated for relieving stresses in calcine-filled canisters. Properties of fission product oxides were examined to elucidate possible adverse corrosive effects at the canister-waste interface. (LK

Occupation times of random walks in confined geometries: From random trap model to diffusion limited reactions

We consider a random walk in confined geometry, starting from a site and eventually reaching a target site. We calculate analytically the distribution of the occupation time on a third site, before reaching the target site. The obtained distribution is exact, and completely explicit in the case or parallepipedic confining domains. We discuss implications of these results in two different fields: The mean first passage time for the random trap model is computed in dimensions greater than 1, and is shown to display a non-trivial dependence with the source and target positions ; The probability of reaction with a given imperfect center before being trapped by another one is also explicitly calculated, revealing a complex dependence both in geometrical and chemical parameters

Immunological correlates of protection mediated by a whole organism,Cryptococcus neoformans, vaccine deficient in chitosan

UNLABELLED: The global burden of infections due to the pathogenic fungus IMPORTANCE: The fungu

Diffusion on random site percolation clusters. Theory and NMR microscopy experiments with model objects

Quasi two-dimensional random site percolation model objects were fabricate based on computer generated templates. Samples consisting of two compartments, a reservoir of H$_2$O gel attached to a percolation model object which was initially filled with D$_2$O, were examined with NMR (nuclear magnetic resonance) microscopy for rendering proton spin density maps. The propagating proton/deuteron inter-diffusion profiles were recorded and evaluated with respect to anomalous diffusion parameters. The deviation of the concentration profiles from those expected for unobstructed diffusion directly reflects the anomaly of the propagator for diffusion on a percolation cluster. The fractal dimension of the random walk, $d_w$, evaluated from the diffusion measurements on the one hand and the fractal dimension, $d_f$, deduced from the spin density map of the percolation object on the other permits one to experimentally compare dynamical and static exponents. Approximate calculations of the propagator are given on the basis of the fractional diffusion equation. Furthermore, the ordinary diffusion equation was solved numerically for the corresponding initial and boundary conditions for comparison. The anomalous diffusion constant was evaluated and is compared to the Brownian case. Some ad hoc correction of the propagator is shown to pay tribute to the finiteness of the system. In this way, anomalous solutions of the fractional diffusion equation could experimentally be verified for the first time.Comment: REVTeX, 12 figures in GIF forma

Effect of Differential N-linked and O-linked Mannosylation on Recognition of Fungal Antigens by Dendritic Cells

BACKGROUND. An experimental approach for improving vaccine efficacy involves targeting antigens to mannose receptors (MRs) on dendritic cells (DCs) and other professional antigen presenting cells. Previously, we demonstrated that mannosylated Pichia pastoris-derived recombinant proteins exhibited increased immunogenicity compared to proteins lacking mannosylation. In order to gain insight into the mechanisms responsible for this observation, the present study examined the cellular uptake of the mannosylated and deglycosylated recombinant proteins. METHODOLOGY/PRINCIPAL FINDINGS. Utilizing transfected cell lines, roles for the macrophage mannose receptor (MMR, CD206) and DC-SIGN (CD209) in the recognition of the mannosylated, but not deglycosylated, antigens were demonstrated. The uptake of mannosylated antigens into murine bone marrow-derived DCs (BMDCs) was inhibited by yeast mannans (YMs), suggesting a mannose-specific C-type lectin receptor-dependent process, while the uptake of deglycosylated antigens remained unaffected. In particular, antigens with both N-linked and extensive O-linked mannosylation showed the highest binding and uptake by BMDCs. Finally, confocal microscopy studies revealed that both mannosylated and deglycosylated P. pastoris-derived recombinant proteins localized in MHC class II+ compartments within BMDCs. CONCLUSIONS/SIGNIFICANCE. Taken together with our previous results, these data suggest that increased uptake by mannose-specific C-type lectin receptors is the major mechanism responsible for the enhanced antigenicity seen with mannosylated proteins. These findings have important implications for vaccine design and contribute to our understanding of how glycosylation affects the immune response to eukaryotic pathogens.National Institutes of Health (RO1 AI25780, RO1 AI37532

Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection

Pulmonary mycoses are often associated with type-2 helper T (Th2) cell responses. However, mechanisms of Th2 cell accumulation are multifactorial and incompletely known. To investigate Th2 cell responses to pulmonary fungal infection, we developed a peptide-MHCII tetramer to track antigen-specific CD4+ T cells produced in response to infection with the fungal pathogen Cryptococcus neoformans. We noted massive accruement of pathologic cryptococcal antigen-specific Th2 cells in the lungs following infection that was coordinated by lung-resident CD11b+ IRF4-dependent conventional dendritic cells. Other researchers have demonstrated that this dendritic cell subset is also capable of priming protective Th17 cell responses to another pulmonary fungal infection, Aspergillus fumigatus. Thus, higher order detection of specific features of fungal infection by these dendritic cells must direct Th2 cell lineage commitment. Since chitin-containing parasites commonly elicit Th2 responses, we hypothesized that recognition of fungal chitin is an important determinant of Th2 cell-mediated mycosis. Using C. neoformans mutants or purified chitin, we found that chitin abundance impacted Th2 cell accumulation and disease. Importantly, we determined Th2 cell induction depended on cleavage of chitin via the mammalian chitinase, chitotriosidase, an enzyme that was also prevalent in humans experiencing overt cryptococcosis. The data presented herein offers a new perspective on fungal disease susceptibility, whereby chitin recognition via chitotriosidase leads to the initiation of harmful Th2 cell differentiation by CD11b+ conventional dendritic cells in response to pulmonary fungal infection